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Wang Z, Li Y, Wang X, Zhang W, Chen Y, Lu X, Jin C, Tu L, Jiang T, Yang Y, Ma X, Zeng J, Wen Y, Efferth T. Precision Strike Strategy for Liver Diseases Trilogy with Xiao-Chai-Hu Decoction: A Meta-Analysis with Machine Learning. PHYTOMEDICINE : INTERNATIONAL JOURNAL OF PHYTOTHERAPY AND PHYTOPHARMACOLOGY 2025; 142:156796. [PMID: 40347886 DOI: 10.1016/j.phymed.2025.156796] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/20/2025] [Revised: 03/30/2025] [Accepted: 04/20/2025] [Indexed: 05/14/2025]
Abstract
BACKGROUND AND PURPOSE The progression from hepatitis to liver fibrosis (LF) and ultimately to hepatic carcinoma (HCC) represents the advanced stages of various liver diseases. Currently, no universal treatment effectively addresses all three conditions. The Traditional Chinese Medicine formula Xiao-Chai-Hu decoction (XCHD) has shown promise in treating hepatitis, inhibiting LF, and serving as an adjunct therapy for HCC. This study evaluates the efficacy and optimal treatment durations of XCHD in managing these liver diseases using meta-analysis and machine learning techniques. METHODS Registered in the PROSPERO database (CRD42024534445), this meta-analysis systematically searched seven databases, including 54 studies with a total of 5,710 patients. Statistical analysis was performed using Stata 17.0. Five machine learning models-Random Forest (RF), XGBoost, Lasso, Multilayer Perceptron (MLP), and a stacking model combining these algorithms-were employed to analyze the data and predict the time-effect relationships. The optimal durations of XCHD treatment for the liver disease trilogy were subsequently projected. RESULTS XCHD significantly improved the primary outcome indicators for hepatitis, liver fibrosis, and HCC. Additionally, XCHD demonstrated a beneficial effect on liver dysfunction caused by these diseases. Machine learning predicted the optimal treatment durations of XCHD as 12 weeks for hepatitis, 20.31 weeks for liver fibrosis, and 12 weeks for HCC. CONCLUSION XCHD is effective in treating the liver disease trilogy, with optimal treatment durations of 12 weeks for hepatitis and HCC, and 20.31 weeks for liver fibrosis. These findings support the potential of XCHD in developing precise clinical strategies for managing liver diseases. This study innovatively integrates meta-analysis with machine learning to determine the optimal treatment durations, providing a novel approach for evidence-based precision medicine in Traditional Chinese Medicine.
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Affiliation(s)
- Zexin Wang
- State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Yubing Li
- State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Xiaobao Wang
- TCM Regulating Metabolic Diseases Key Laboratory of Sichuan Province, Department of Gastroenterology, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Wenwen Zhang
- State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Yuan Chen
- State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Xiaohua Lu
- Department of Pharmaceutical Biology, Institute of Pharmaceutical and Biomedical Sciences, Johannes Gutenberg University, Mainz, Germany
| | - Chunmei Jin
- Department of Pharmaceutical Biology, Institute of Pharmaceutical and Biomedical Sciences, Johannes Gutenberg University, Mainz, Germany
| | - Lang Tu
- West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, China
| | - Tao Jiang
- State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Yiqin Yang
- Hunan Provincial Key Laboratory of the Research and Development of Novel Pharmaceutical Preparations, Changsha Medical University, Changsha, China
| | - Xiao Ma
- State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China.
| | - Jinhao Zeng
- TCM Regulating Metabolic Diseases Key Laboratory of Sichuan Province, Department of Gastroenterology, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, China.
| | - Yueqiang Wen
- School of Basic Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, China.
| | - Thomas Efferth
- Department of Pharmaceutical Biology, Institute of Pharmaceutical and Biomedical Sciences, Johannes Gutenberg University, Mainz, Germany.
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Zhang J, Wang N, Xin T, Zhu X, Lang S, Ge X. Liquiritin mitigates lower extremity deep vein thrombosis by inhibiting inflammation and oxidative stress via the NF-κB signaling pathway. Thromb J 2025; 23:51. [PMID: 40394684 PMCID: PMC12090432 DOI: 10.1186/s12959-025-00739-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2025] [Accepted: 05/09/2025] [Indexed: 05/22/2025] Open
Abstract
BACKGROUND Lower extremity deep vein thrombosis (LEDVT) is a common vascular disease, with its pathogenesis mainly involving inflammatory responses and oxidative stress. Liquiritin (LIQ) is a flavonoid that exhibits pharmacological effects such as anti-inflammatory and antioxidant properties. This study aimed to investigate the role of LIQ in LEDVT and its potential mechanisms. METHODS We established an LEDVT model in mice by ligating the inferior vena cava (IVC) and performed in vitro experiments by stimulating human umbilical vein endothelial cells (HUVECs) with IL-1β (10 ng/mL) to simulate endothelial cell injury. RESULTS We found that LIQ significantly reduced the size and weight of thrombi and decreased the concentrations of inflammatory factors TNF-α and IL-6 in the IVC of LEDVT mice. Furthermore, LIQ inhibited the secretion of prothrombotic mediators such as tissue factor (TF) and vascular cell adhesion molecule-1 (VCAM-1). Administration of LIQ resulted in a notable reduction in immune inflammatory cells in the IVC of LEDVT mice. LIQ also demonstrated antioxidant properties, as the treatment of LIQ enhanced SOD activity and restored ROS levels to normal in the IVC. Similarly, LIQ reduced the formation of inflammatory factors and the secretion of prothrombotic mediators by HUVECs while inhibiting oxidative stress in HUVECs. Finally, LIQ effectively suppressed the levels of phosphorylated p65 in both the IVC and HUVECs. CONCLUSIONS LIQ reduces inflammatory responses and oxidative stress in LEDVT by inhibiting the NF-κB signaling pathway. This finding provides new insights into the prevention and treatment of LEDVT.
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Affiliation(s)
- Jiacheng Zhang
- Department of Emergency and Critical Care Medicine, Wuxi 9th People's Hospital Affiliated to Soochow University, Liangxi Road 999, Wuxi, Jiangsu, 214000, People's Republic of China
| | - Nan Wang
- Department of Emergency and Critical Care Medicine, Wuxi 9th People's Hospital Affiliated to Soochow University, Liangxi Road 999, Wuxi, Jiangsu, 214000, People's Republic of China
| | - Tianyou Xin
- Department of Ultrasound, Wuxi 9th People's Hospital Affiliated to Soochow University, Wuxi, Jiangsu, People's Republic of China
| | - Xiaojun Zhu
- Department of Vascular Surgery, Wuxi 9th People's Hospital Affiliated to Soochow University, Wuxi, Jiangsu, People's Republic of China
| | - Shengkun Lang
- Department of Neurosurgery, The First Medical Center of Chinese PLA General Hospital, Fuxing Road 28, Beijing, People's Republic of China.
| | - Xin Ge
- Department of Emergency and Critical Care Medicine, Wuxi 9th People's Hospital Affiliated to Soochow University, Liangxi Road 999, Wuxi, Jiangsu, 214000, People's Republic of China.
- Orthopedic Institution of Wuxi City, Liangxi Road 999, Wuxi, Jiangsu, 214000, People's Republic of China.
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Qiu S, Sun J, Su S, Wu W, Zhang J, Qi J, Xu Y. Traditional Chinese Medicine YangxinDingji alleviates arrhythmias through inhibition of sodium and L-type calcium channels. JOURNAL OF ETHNOPHARMACOLOGY 2025; 347:119803. [PMID: 40239882 DOI: 10.1016/j.jep.2025.119803] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/25/2025] [Revised: 04/09/2025] [Accepted: 04/11/2025] [Indexed: 04/18/2025]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE The Chinese herbal formula YangxinDingji (YXDJ), derived from the classic ancient formula Zhigancao decoction that originated from Zhang Zhongjing's "shang han lun", is a modern preparation of a classic prescription, and is used for arrhythmia treatment in China. However, its antiarrhythmic mechanisms are not fully elucidated. AIM OF THE STUDY This study aimed to investigate the pharmacological and molecular mechanisms of YXDJ. MATERIALS AND METHODS Antiarrhythmic effects were evaluated in isolated guinea pig hearts subjected to ischemia/reperfusion (I/R) or isoproterenol (ISO) challenge, and in human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) utilizing a multi-electrode array (MEA). Patch clamp recordings assessed the effects of YXDJ on sodium (INa, INa-L) and L-type calcium (ICa-L) currents, while potassium currents (IKr, IKs) were studied in heterologous cells. Optical mapping observed electrical activities and calcium transients. RESULTS YXDJ pretreatment at concentrations of 0.25, 0.5, and 1.0 mg/ml effectively prevented ventricular arrhythmias induced by I/R or ISO challenge, and mitigated electrical stimulation-induced arrhythmias in hiPSC-CMs. YXDJ inhibited INa, INa-L, and ICa-L currents in a concentration-dependent manner without affecting IKr and IKs, inhibited abnormal electrical activities and excitation reentry, decreased action potential duration dispersion and heterogeneity of excitation conduction, and restored intracellular calcium homeostasis. CONCLUSIONS Our results demonstrate that YXDJ exerts its antiarrhythmic effect through the inhibition of inward depolarizing currents, which prevents alterations in left ventricular repolarization dispersion. This leads to synchronized repolarization and a reduction in excitation reentry. Collectively, these findings suggest that YXDJ is a promising candidate for the treatment of arrhythmias.
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MESH Headings
- Animals
- Guinea Pigs
- Drugs, Chinese Herbal/pharmacology
- Drugs, Chinese Herbal/therapeutic use
- Arrhythmias, Cardiac/drug therapy
- Arrhythmias, Cardiac/metabolism
- Arrhythmias, Cardiac/physiopathology
- Myocytes, Cardiac/drug effects
- Myocytes, Cardiac/metabolism
- Humans
- Anti-Arrhythmia Agents/pharmacology
- Anti-Arrhythmia Agents/therapeutic use
- Calcium Channels, L-Type/metabolism
- Calcium Channels, L-Type/drug effects
- Male
- Induced Pluripotent Stem Cells/drug effects
- Calcium Channel Blockers/pharmacology
- Calcium Channel Blockers/therapeutic use
- Medicine, Chinese Traditional
- Sodium Channels/metabolism
- Action Potentials/drug effects
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Affiliation(s)
- Suhua Qiu
- Department of Pharmacology, Hebei Medical University, Shijiazhuang, 050017, China; Key Laboratory of New Drug Pharmacology and Toxicology, Shijiazhuang, 050017, China; Key Laboratory of Neural and Vascular Biology, Ministry of Education, Shijiazhuang, 050017, China.
| | - Jinglei Sun
- Department of Pharmacology, Hebei Medical University, Shijiazhuang, 050017, China; Key Laboratory of New Drug Pharmacology and Toxicology, Shijiazhuang, 050017, China; Key Laboratory of Neural and Vascular Biology, Ministry of Education, Shijiazhuang, 050017, China.
| | - Shi Su
- Department of Pharmacology, Hebei Medical University, Shijiazhuang, 050017, China; Key Laboratory of New Drug Pharmacology and Toxicology, Shijiazhuang, 050017, China; Key Laboratory of Neural and Vascular Biology, Ministry of Education, Shijiazhuang, 050017, China.
| | - Wenting Wu
- Department of Pharmacology, Hebei Medical University, Shijiazhuang, 050017, China; Key Laboratory of New Drug Pharmacology and Toxicology, Shijiazhuang, 050017, China; Key Laboratory of Neural and Vascular Biology, Ministry of Education, Shijiazhuang, 050017, China.
| | - Jiali Zhang
- Department of Pharmacology, Hebei Medical University, Shijiazhuang, 050017, China; Key Laboratory of New Drug Pharmacology and Toxicology, Shijiazhuang, 050017, China; Key Laboratory of Neural and Vascular Biology, Ministry of Education, Shijiazhuang, 050017, China.
| | - Jinlong Qi
- Department of Pharmacology, Hebei Medical University, Shijiazhuang, 050017, China; Key Laboratory of New Drug Pharmacology and Toxicology, Shijiazhuang, 050017, China; Key Laboratory of Neural and Vascular Biology, Ministry of Education, Shijiazhuang, 050017, China.
| | - Yanfang Xu
- Department of Pharmacology, Hebei Medical University, Shijiazhuang, 050017, China; Key Laboratory of New Drug Pharmacology and Toxicology, Shijiazhuang, 050017, China; Key Laboratory of Neural and Vascular Biology, Ministry of Education, Shijiazhuang, 050017, China.
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Zhao L, Zhang J, He J, Ma X, Yu Z, Yong Y, Li Y, Ju X, Liu X. Biochemical impact of ALAEm supplementation in late gestation on the reproductive performance of sows. Front Vet Sci 2025; 12:1548263. [PMID: 40336816 PMCID: PMC12055862 DOI: 10.3389/fvets.2025.1548263] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2024] [Accepted: 04/03/2025] [Indexed: 05/09/2025] Open
Abstract
Adding plant extracts to diets to enhance sow performance and health is widely regarded as a healthy and sustainable practice. In promoting antibiotic-free farming, plant extracts have emerged as a leading solution for enhancing sow fertility through nutritional strategies. The aim of this study was to investigate the biochemical impacts of supplementation of sows with ALAEm (composed of nine plant extracts) on blood and placental indices of sows in late gestation. The components of ALAEm were determined by UPLC-MS/MS. 196 normal gestation parturient sows were randomly allocated into two groups (n = 98 per group): the control group and the test group fed 20 g/d ALAEm supplementation at 74-114 d of gestation. The study examined the various clinical indexes in the blood, the expression of genes and proteins and metabolomics in the placenta. Dietary ALAEm supplementation improved sow reproductive performance (total number of piglets born alive, number of piglets weaned, wean weight), serum biochemical indices, placental structure and increased gene and protein expression of ZO-1, Claudin-1 and other placental junction-associated factors. ALAEm attenuated placental tissue oxidation, inflammation, and apoptosis, promoted placental growth (EGF and IGF-1) and angiogenesis factors (VEGFA, PIGF and other factors), and increased the nutrient transport in placental (GLUT1 and SNAT2). Dietary ALAEm supplementation decreased the number of metabolites associated with lipid metabolism through alpha-linolenic acid metabolism. Therefore, dietary supplementation of ALAEm in the late gestation may improve fertility by reducing the levels of inflammation, oxidation and apoptosis in placental tissues via the EGFR/VEGFR2-PI3K-AKT1 pathway, promoting placental growth, angiogenesis and nutrient transport, and altering the levels of placental lipid metabolites via α-linolenic acid metabolism.
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Affiliation(s)
| | | | | | | | | | | | | | | | - Xiaoxi Liu
- Department of Veterinary Medicine, College of Coastal Agricultural Sciences, Guangdong Ocean University, Zhanjiang, China
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Zhang L, Wang W, Liu X, Yan K, Li Q, Li M, Li C, Li Y, Chen L. Traditional Chinese medicine compounds modulate signaling pathways to improve cardiac-related pathology. Front Pharmacol 2025; 16:1499060. [PMID: 40242436 PMCID: PMC12000890 DOI: 10.3389/fphar.2025.1499060] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2024] [Accepted: 03/20/2025] [Indexed: 04/18/2025] Open
Abstract
Cardiovascular disease poses a significant risk to human health and remains the leading cause of illness and death globally, with its incidence continuing to rise. The intricate pathophysiological mechanisms of CVDs include inflammation, oxidative stress, autophagy, and myocardial fibrosis. In light of these underlying mechanisms, traditional Chinese medicine (TCM) and its constituents have demonstrated distinct advantages in managing CVDs. By exerting synergistic effects across multiple components and targets, traditional Chinese medicine can modulate the inflammatory response, mitigate oxidative stress, regulate excessive autophagy, and enhance myocardial fibrosis repair. This article reviews the latest advancements in understanding how TCM compounds regulate signaling pathways involved in the treatment of CVDs.
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Affiliation(s)
- Luwen Zhang
- The First Clinical Medical College of Henan University of Chinese Medicine, Zhengzhou, Henan, China
- The First Affiliated Hospital of Henan University of Chinese Medicine, Heart Center/National Regional (Traditional Chinese Medicine) Cardiovascular Diagnosis and Treatment Center, Zhengzhou, Henan, China
| | - Wei Wang
- The First Affiliated Hospital of Henan University of Chinese Medicine, Henan Province Traditional Chinese Medicine Epidemic Diseases Engineering Research Center, Zhengzhou, Henan, China
| | - Xincan Liu
- The First Affiliated Hospital of Henan University of Chinese Medicine, Heart Center/National Regional (Traditional Chinese Medicine) Cardiovascular Diagnosis and Treatment Center, Zhengzhou, Henan, China
| | - Kuipo Yan
- The First Affiliated Hospital of Henan University of Chinese Medicine, Heart Center/National Regional (Traditional Chinese Medicine) Cardiovascular Diagnosis and Treatment Center, Zhengzhou, Henan, China
| | - Qiang Li
- The First Affiliated Hospital of Hena University of Chinese Medicine, Henan Key Laboratory of Viral Diseases Prevention and Treatment of Traditional Chinese Medicine, Zhengzhou, Henan, China
| | - Ming Li
- The First Affiliated Hospital of Henan University of Chinese Medicine, Heart Center/National Regional (Traditional Chinese Medicine) Cardiovascular Diagnosis and Treatment Center, Zhengzhou, Henan, China
| | - Chunying Li
- The First Clinical Medical College of Henan University of Chinese Medicine, Zhengzhou, Henan, China
- The First Affiliated Hospital of Henan University of Chinese Medicine, Heart Center/National Regional (Traditional Chinese Medicine) Cardiovascular Diagnosis and Treatment Center, Zhengzhou, Henan, China
| | - Yanxin Li
- The First Clinical Medical College of Henan University of Chinese Medicine, Zhengzhou, Henan, China
- The First Affiliated Hospital of Henan University of Chinese Medicine, Heart Center/National Regional (Traditional Chinese Medicine) Cardiovascular Diagnosis and Treatment Center, Zhengzhou, Henan, China
| | - Lei Chen
- The First Affiliated Hospital of Henan University of Chinese Medicine, Heart Center/National Regional (Traditional Chinese Medicine) Cardiovascular Diagnosis and Treatment Center, Zhengzhou, Henan, China
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Tang X, Wang X, Feng B, Cui Y. Simultaneous Determination of Eight Bioactive Components of Huangqin Decoction in Rat Plasma by Ultra-high-performance Liquid Chromatography-tandem Mass Spectrometry and Its Application to Comparative Pharmacokinetic Study of Huangqin Decoction in Ulcerative Colitis and Normal Rats. J Sep Sci 2025; 48:e70140. [PMID: 40230313 DOI: 10.1002/jssc.70140] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/12/2025] [Revised: 03/14/2025] [Accepted: 04/02/2025] [Indexed: 04/16/2025]
Abstract
Huangqin Decoction (HQD), a traditional Chinese medicine prescription, was first recorded in Treatise on Febrile Diseases 2000 years ago. It is widely used in the treatment of ulcerative colitis (UC). The purpose of the study was to investigate and compare the pharmacokinetic behaviors of the main bioactive components of HQD in UC and normal rats. A simple, rapid, and sensitive liquid chromatography-tandem mass spectrometry method was developed for the simultaneous determination of eight components of HQD in rat plasma. Analytes were separated on a C18 column under gradient elution with a mobile phase consisting of 0.1% formic acid in water and 0.1% formic acid in acetonitrile. Multiple reaction monitoring mode was used to acquire mass transitions. Method validation results showed good specificity and good linearity, with a limit of quantification ranging from 2.5 to 5.0 ng/mL which were sufficient for the pharmacokinetic study. The accuracy and precision were within 12.1% and 11.8%, respectively. Extraction recovery and matrix effect were from 81.8% to 98.8% and 83.6% to 98.4%, respectively. The relative error values of stability under different storage conditions were within 12.8%. The method was successfully applied to study the pharmacokinetics of eight components in UC and normal rat plasma after oral administration of HQD. Pharmacokinetic parameters of analytes were calculated. Results showed that the pharmacokinetic behaviors in UC and normal rats were significantly different, especially time to peak drug concentration (Tmax), peak concentration (Cmax), and area under the curve (AUC). In general, the Cmax of all analytes and AUCs of most analytes in UC rats were markedly lower than in normal rats, which might be related to the pathological state of UC influencing the exposure levels of bioactive components of HQD, and reducing the absorption of them, resulting differences in pharmacokinetic behaviors. This study could provide a reference for the future clinical application of this classical traditional Chinese medicine formula.
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Affiliation(s)
- Xinmiao Tang
- School of Pharmacy, Jilin Medical University, Jilin, P. R. China
| | - Xing Wang
- School of Pharmacy, Jilin Medical University, Jilin, P. R. China
- School of Pharmacy, Yanbian University, Yanji, P. R. China
| | - Bo Feng
- School of Pharmacy, Jilin Medical University, Jilin, P. R. China
| | - Yue Cui
- School of Pharmacy, Jilin Medical University, Jilin, P. R. China
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Lu Y, Ding Z, Zhang D, Zhu F, Gao B. Integrated Metabolomic and Transcriptomic Analysis Reveals the Pharmacological Effects and Differential Mechanisms of Isoflavone Biosynthesis in Four Species of Glycyrrhiza. Int J Mol Sci 2025; 26:2539. [PMID: 40141180 PMCID: PMC11942288 DOI: 10.3390/ijms26062539] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2025] [Revised: 03/05/2025] [Accepted: 03/10/2025] [Indexed: 03/28/2025] Open
Abstract
Licorice (Glycyrrhiza L.) is a globally popular medicinal and edible plant, with nearly 30 species distributed across all continents. The usable part is primarily the root. To understand the metabolic differences among different Glycyrrhiza species, we selected four species and performed comprehensive analyses of their roots. Metabolomic profiling was conducted using UPLC-MS/MS and GC-MS, while transcriptomic analysis was carried out using RNA-sequencing. A total of 2716 metabolites were identified, including flavonoids (527 types) and terpenoids (251 types), among various other components. Subsequently, network pharmacology was employed to explore the medicinal value and potential pharmacological ingredients of these metabolites. Joint analysis of transcriptomic and metabolomic data revealed significant differences in differentially accumulated metabolites (DAMs) and differentially expressed genes (DEGs) in pairwise comparisons among the four species. These differences were primarily enriched in the isoflavone pathway. Further investigation into the regulatory mechanisms of isoflavone biosynthesis in different Glycyrrhiza species identified key genes and metabolites involved in isoflavone biosynthesis. Finally, we made reasonable predictions of the potential suitable habitats for the four Glycyrrhiza species, aiming to provide new insights for the development and utilization of licorice resources. The results of this study can serve as a basis for the development and utilization of licorice and for in-depth research on the regulation of isoflavone biosynthesis in licorice.
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Affiliation(s)
- Yuanfeng Lu
- State Key Laboratory of Ecological Safety and Sustainable Development in Arid Lands, Xinjiang Institute of Ecology and Geography, Chinese Academy of Sciences, Urumqi 830011, China; (Y.L.); (Z.D.); (D.Z.)
- Xinjiang Key Lab of Conservation and Utilization of Plant Gene Resources, Xinjiang Institute of Ecology and Geography, Chinese Academy of Sciences, Urumqi 830011, China
- The Southern Modern Forestry Collaborative Innovation Center, State Key Laboratory of Tree Genetics and Breeding, Key Laboratory of State Forestry and Grassland Administration on Subtropical Forest Biodiversity Conservation, College of Life Sciences, Nanjing Forestry University, Nanjing 210008, China
| | - Zhen Ding
- State Key Laboratory of Ecological Safety and Sustainable Development in Arid Lands, Xinjiang Institute of Ecology and Geography, Chinese Academy of Sciences, Urumqi 830011, China; (Y.L.); (Z.D.); (D.Z.)
- University of Chinese Academy of Sciences, Beijing 100049, China
| | - Daoyuan Zhang
- State Key Laboratory of Ecological Safety and Sustainable Development in Arid Lands, Xinjiang Institute of Ecology and Geography, Chinese Academy of Sciences, Urumqi 830011, China; (Y.L.); (Z.D.); (D.Z.)
- Xinjiang Key Lab of Conservation and Utilization of Plant Gene Resources, Xinjiang Institute of Ecology and Geography, Chinese Academy of Sciences, Urumqi 830011, China
| | - Fuyuan Zhu
- State Key Laboratory of Ecological Safety and Sustainable Development in Arid Lands, Xinjiang Institute of Ecology and Geography, Chinese Academy of Sciences, Urumqi 830011, China; (Y.L.); (Z.D.); (D.Z.)
- Xinjiang Key Lab of Conservation and Utilization of Plant Gene Resources, Xinjiang Institute of Ecology and Geography, Chinese Academy of Sciences, Urumqi 830011, China
- The Southern Modern Forestry Collaborative Innovation Center, State Key Laboratory of Tree Genetics and Breeding, Key Laboratory of State Forestry and Grassland Administration on Subtropical Forest Biodiversity Conservation, College of Life Sciences, Nanjing Forestry University, Nanjing 210008, China
| | - Bei Gao
- State Key Laboratory of Ecological Safety and Sustainable Development in Arid Lands, Xinjiang Institute of Ecology and Geography, Chinese Academy of Sciences, Urumqi 830011, China; (Y.L.); (Z.D.); (D.Z.)
- Xinjiang Key Lab of Conservation and Utilization of Plant Gene Resources, Xinjiang Institute of Ecology and Geography, Chinese Academy of Sciences, Urumqi 830011, China
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Amrutha S, Abhinand CS, Upadhyay SS, Parvaje R, Prasad TSK, Modi PK. Network pharmacology and metabolomics analysis of Tinospora cordifolia reveals BACE1 and MAOB as potential therapeutic targets for neuroprotection in Alzheimer's disease. Sci Rep 2025; 15:8103. [PMID: 40057579 PMCID: PMC11890609 DOI: 10.1038/s41598-025-92756-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/05/2024] [Accepted: 03/03/2025] [Indexed: 05/13/2025] Open
Abstract
Tinospora cordifolia has been used for thousands of years to treat various health conditions, including neurodegenerative diseases. The study aimed to elucidate the mechanism of action and protein targets of T. cordifolia in the context of Alzheimer's disease through untargeted metabolomics and network pharmacology. LC-MS/MS analysis resulted in 1186 metabolites, including known bioactive compounds such as liquiritin, Plastoquinone 3, and Shoyuflavone A, to name a few. The network pharmacology analysis highlighted the metabolite-protein interaction with the enrichment of 591 human proteins, including neurotransmitter receptors and other regulatory proteins. Pathway analysis highlighted the enrichment of cAMP, mTOR, MAPK, and PI3K-Akt signaling pathways along with cholinergic, dopaminergic, serotonergic, glutamatergic synapse, and apoptosis. The docking results suggest that T. cordifolia metabolites could interact with key Alzheimer's disease targets BACE1 and MAO-B, suggesting its role in neuroprotection. These findings provide insights into the biochemical pathways underlying T. cordifolia's therapeutic effects and provides a foundation for future exploration of T. cordifolia in the context of translational research.
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Affiliation(s)
- S Amrutha
- Center for Systems Biology and Molecular Medicine, Yenepoya Research Centre, Yenepoya (Deemed to be University), Mangalore, 575018, India
| | - Chandran S Abhinand
- Center for Systems Biology and Molecular Medicine, Yenepoya Research Centre, Yenepoya (Deemed to be University), Mangalore, 575018, India
| | - Shubham Sukerndeo Upadhyay
- Center for Systems Biology and Molecular Medicine, Yenepoya Research Centre, Yenepoya (Deemed to be University), Mangalore, 575018, India
| | | | | | - Prashant Kumar Modi
- Center for Systems Biology and Molecular Medicine, Yenepoya Research Centre, Yenepoya (Deemed to be University), Mangalore, 575018, India.
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Ji Q, Liu Y, Zhang H, Gao Y, Ding Y, Ding Y, Xie J, Zhang J, Jin X, Lai B, Chen C, Wang J, Gao W, Mei K. Structural Insights into the Substrate Recognition of Ginsenoside Glycosyltransferase Pq3-O-UGT2. ADVANCED SCIENCE (WEINHEIM, BADEN-WURTTEMBERG, GERMANY) 2025; 12:e2413185. [PMID: 39887940 PMCID: PMC11923902 DOI: 10.1002/advs.202413185] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/18/2024] [Revised: 12/09/2024] [Indexed: 02/01/2025]
Abstract
Ginsenosides are a group of tetracyclic triterpenoids with promising health benefits, consisting of ginseng aglycone attached to various glycans. Pq3-O-UGT2, an important UDP-dependent glycosyltransferase (UGT), catalyzes the production of Ginsenoside Rg3 and Rd by extending the glycan chain of Ginsenoside Rh2 and F2, respectively, with higher selectivity for F2. However, the mechanism underlying its substrate recognition remains unclear. In this study, the crystal structures of Pq3-O-UGT2 in complex with its acceptor substrates are solved. The structures revealed a Nα5-oriented acceptor binding pocket in Pq3-O-UGT2, shaped by the unique conformation of the Nα5-Nα6 linker. Hydrophobic interactions play a pivotal role in the recognition of both Rh2 and F2, while hydrogen bonds specifically aid in F2 recognition due to its additional glucose moiety. The hydrophobic nature of the acceptor binding pocket also enables Pq3-O-UGT2 to recognize flavonoids. Overall, this study provides novel insights into the substrate recognition mechanisms of ginsenoside UGTs, advancing the understanding of their function and specificity.
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Affiliation(s)
- Qiushuang Ji
- School of Pharmaceutical Science and TechnologyFaculty of MedicineTianjin UniversityTianjin300072China
- Department of PharmacologyHebei Medical UniversityShijiazhuangHebei050017China
| | - Yirong Liu
- School of Pharmaceutical Science and TechnologyFaculty of MedicineTianjin UniversityTianjin300072China
| | - Huanyu Zhang
- School of Pharmaceutical Science and TechnologyFaculty of MedicineTianjin UniversityTianjin300072China
| | - Yan Gao
- Instrument Analytical CenterSchool of Pharmaceutical Science and TechnologyFaculty of MedicineTianjin UniversityTianjin300072China
| | - Yixin Ding
- School of Pharmaceutical Science and TechnologyFaculty of MedicineTianjin UniversityTianjin300072China
| | - Yuanyuan Ding
- School of Pharmaceutical Science and TechnologyFaculty of MedicineTianjin UniversityTianjin300072China
| | - Jing Xie
- School of Pharmaceutical Science and TechnologyFaculty of MedicineTianjin UniversityTianjin300072China
| | - Jianyu Zhang
- School of Pharmaceutical Science and TechnologyFaculty of MedicineTianjin UniversityTianjin300072China
| | - Xinghua Jin
- Instrument Analytical CenterSchool of Pharmaceutical Science and TechnologyFaculty of MedicineTianjin UniversityTianjin300072China
| | - Bin Lai
- BMBF junior research group BiophotovoltaicsDepartment of Microbial BiotechnologyHelmholtz Centre for Environmental Research – UFZ04318LeipzigGermany
| | - Cheng Chen
- School of Life SciencesTianjin UniversityTianjin300072China
| | - Juan Wang
- School of Pharmaceutical Science and TechnologyFaculty of MedicineTianjin UniversityTianjin300072China
- State Key Laboratory for Quality Ensurance and Sustainable Use of Dao‐di HerbsBeijng100700China
- State Key Laboratory of Synthetic BiologyTianjin UniversityTianjin300072China
| | - Wenyuan Gao
- School of Pharmaceutical Science and TechnologyFaculty of MedicineTianjin UniversityTianjin300072China
- State Key Laboratory for Quality Ensurance and Sustainable Use of Dao‐di HerbsBeijng100700China
- State Key Laboratory of Synthetic BiologyTianjin UniversityTianjin300072China
| | - Kunrong Mei
- School of Pharmaceutical Science and TechnologyFaculty of MedicineTianjin UniversityTianjin300072China
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10
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Wang RY, Huang JS, Tan WW, Lu R, Yang T. Crystalline Liquiritigenin and Liquiritin: Structural Characterization, Molecular Docking Studies, and Anti-Amyloid-β Evaluation in Caenorhabditis elegans. ACS OMEGA 2025; 10:7112-7119. [PMID: 40028075 PMCID: PMC11866007 DOI: 10.1021/acsomega.4c10199] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/09/2024] [Revised: 12/30/2024] [Accepted: 01/16/2025] [Indexed: 03/05/2025]
Abstract
Two new crystalline compounds, named [LG·H2O] n (1; LG = liquiritigenin) and [LQ·C2H5OH·H2O] n (2; LQ = liquiritin), have been synthesized and structurally characterized by single-crystal and powder X-ray diffraction, thermogravimetric analyses (TGA), nuclear magnetic resonance (NMR), high-resolution mass spectrometry (HR-MS), and infrared spectra (IR). 1 and 2 crystallize in space groups Pna21 and P212121, respectively. In the structure of 1, liquiritigenin and water molecules are connected by hydrogen bonds for the construction of a novel 3,5-connected network topology with a point symbol of (63)(67·83), in which each liquiritigenin and water molecule acts as a 5-connected and 3-connected node, respectively. Both 1 and 2 reduce amyloid-β-induced toxicity in Caenorhabditis elegans (CL4176 strain) by improving the expression level of SOD. Gene expression studies by RT-qPCR indicate upregulation of skn-1 and sod-3 expression while downregulation of daf-16 and hsf-1 expression in C. elegans. Molecular docking studies indicate that LG and LQ combine well with vascular endothelial growth factor A (VEGFA), with free binding energies calculated to be -6.7 and -7.9 kcal·mol-1, respectively. Moreover, the anti-amyloid-β ability of crystalline and amorphous LG or LQ has been studied.
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Affiliation(s)
- Ruo-Yi Wang
- School
of Pharmaceutical Sciences, Guangxi University
of Chinese Medicine, Nanning 530200, P. R. China
| | - Jin-Shuang Huang
- School
of Pharmaceutical Sciences, Guangxi University
of Chinese Medicine, Nanning 530200, P. R. China
| | - Wen-Wu Tan
- School
of Pharmaceutical Sciences, Guangxi University
of Chinese Medicine, Nanning 530200, P. R. China
| | - Rumei Lu
- School
of Pharmaceutical Sciences, Guangxi University
of Chinese Medicine, Nanning 530200, P. R. China
| | - Tao Yang
- School
of Pharmaceutical Sciences, Guangxi University
of Chinese Medicine, Nanning 530200, P. R. China
- Guangxi
Key Laboratory of Marine Drugs, Nanning 530200, P. R. China
- University
Engineering Research Center of Characteristic Traditional Chinese
Medicine and Ethnomedicine, Guangxi, Nanning 530200, P. R. China
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11
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Wang GX, Fei WC, Zhi LL, Bai XD, You B. Fermented tea leave extract against oxidative stress and ageing of skin in vitro and in vivo. Int J Cosmet Sci 2025; 47:1-17. [PMID: 39119798 DOI: 10.1111/ics.12976] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2023] [Revised: 04/12/2024] [Accepted: 04/19/2024] [Indexed: 08/10/2024]
Abstract
OBJECTIVE The objective is to develop a natural and stable anti-oxidative stress and anti-ageing ingredient. In this study, we evaluated the changes in white tea leaves fermented with Eurotium cristatum PLT-PE and Saccharomyces boulardii PLT-HZ and their efficacy against skin oxidative stress. METHODS We employed untargeted metabolomics technology to analyse the differential metabolites between tea extract (TE) and fermented tea extract (FTE). In vitro, using H2O2-induced HaCaT cells, we evaluated cell vitality, ROS, and inflammatory factors (TNF-α, IL-1β, and IL-6). Additionally, we verified the effects on the extracellular matrix and nuclear DNA using fibroblasts or reconstructed skin models. We measured skin hydration, elasticity, wrinkle area, wrinkle area ratio, erythema area, and erythema area ratio in volunteers after using an emulsion containing 3% FTE for 28 and 56 days. RESULTS Targeted metabolomics analysis of white tea leaves yielded more than 20 differential metabolites with antioxidant and anti-inflammatory activities, including amino acids, polypeptides, quercetin, and liquiritin post-fermentation. FTE, compared to TE, can significantly reduce reactive oxygen species (ROS) and protect against oxidative stress-induced skin damage in H2O2-induced HaCaT cells. FTE can inhibit H2O2-induced collagen degradation by suppressing the MAPK/c-Jun signalling pathway and can also mitigate the reactive oxygen species damage to nuclear DNA. Clinical studies showed that the volunteers' stratum corneum water content, skin elasticity, wrinkle area, wrinkle area ratio, erythema area, and erythema area ratio significantly improved from the baseline after 28 and 56 days of FTE use. CONCLUSION This study contributes to the growing body of literature supporting the protective effects against skin oxidative stress and ageing from fermented plant extracts. Moreover, our findings might inspire multidisciplinary efforts to investigate new fermentation techniques that could produce even more potent anti-ageing solutions.
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Affiliation(s)
| | - Wei-Cheng Fei
- R&D Center of Shanghai Huiwen Biotech Co., Ltd, Shanghai, China
| | | | - Xue-Dong Bai
- R&D Center of Shanghai Huiwen Biotech Co., Ltd, Shanghai, China
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12
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Wang B, Wang J, Liu C, Li C, Meng T, Chen J, Liu Q, He W, Liu Z, Zhou Y. Ferroptosis: Latest evidence and perspectives on plant-derived natural active compounds mitigating doxorubicin-induced cardiotoxicity. J Appl Toxicol 2025; 45:135-158. [PMID: 39030835 DOI: 10.1002/jat.4670] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2024] [Revised: 06/24/2024] [Accepted: 06/27/2024] [Indexed: 07/22/2024]
Abstract
Doxorubicin (DOX) is a chemotherapy drug widely used in clinical settings, acting as a first-line treatment for various malignant tumors. However, its use is greatly limited by the cardiotoxicity it induces, including doxorubicin-induced cardiomyopathy (DIC). The mechanisms behind DIC are not fully understood, but its potential biological mechanisms are thought to include oxidative stress, inflammation, energy metabolism disorders, mitochondrial damage, autophagy, apoptosis, and ferroptosis. Recent studies have shown that cardiac injury induced by DOX is closely related to ferroptosis. Due to their high efficacy, availability, and low side effects, natural medicine treatments hold strong clinical potential. Currently, natural medicines have been shown to mitigate DOX-induced ferroptosis and ease DIC through various functions such as antioxidation, iron ion homeostasis correction, lipid metabolism regulation, and mitochondrial function improvement. Therefore, this review summarizes the mechanisms of ferroptosis in DIC and the regulation by natural plant products, with the expectation of providing a reference for future research and development of inhibitors targeting ferroptosis in DIC. This review explores the mechanisms of ferroptosis in doxorubicin-induced cardiomyopathy (DIC) and summarizes how natural plant products can alleviate DIC by inhibiting ferroptosis through reducing oxidative stress, correcting iron ion homeostasis, regulating lipid metabolism, and improving mitochondrial function.
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Affiliation(s)
- Boyu Wang
- Heilongjiang University of Chinese Medicine, Harbin, China
| | - Jiameng Wang
- Heilongjiang University of Chinese Medicine, Harbin, China
| | - Changxing Liu
- Heilongjiang University of Chinese Medicine, Harbin, China
| | - Chengjia Li
- Heilongjiang University of Chinese Medicine, Harbin, China
| | - Tianwei Meng
- Heilongjiang University of Chinese Medicine, Harbin, China
| | - Jia Chen
- Heilongjiang University of Chinese Medicine, Harbin, China
| | - Qingnan Liu
- Heilongjiang University of Chinese Medicine, Harbin, China
| | - Wang He
- First Affiliated Hospital of Heilongjiang University of Chinese Medicine, Harbin, China
| | - Zhiping Liu
- First Affiliated Hospital of Heilongjiang University of Chinese Medicine, Harbin, China
| | - Yabin Zhou
- First Affiliated Hospital of Heilongjiang University of Chinese Medicine, Harbin, China
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13
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Xiao C, Wang Y, Liu J, Li X, Wang P, Zhou J, Xiu H, Lu S, Zhu H, Wang R. Mechanism of Fangji Huangqi decoction against acute kidney injury based on network pharmacology and experimental validation. PHYTOMEDICINE : INTERNATIONAL JOURNAL OF PHYTOTHERAPY AND PHYTOPHARMACOLOGY 2025; 136:156345. [PMID: 39742571 DOI: 10.1016/j.phymed.2024.156345] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/23/2024] [Revised: 05/21/2024] [Accepted: 10/07/2024] [Indexed: 01/03/2025]
Abstract
BACKGROUND Fangji Huangqi Decoction (FJHQD), a famous Traditional Chinese Medicine (TCM) formula, has been widely applied in improving renal function. However, the interaction of bioactives from FJHQD with the targets involved in acute renal injury (AKI) has not been elucidated yet. PURPOSE A network pharmacology-based approach combined with molecular docking and in vitro and in vivo validation was performed to determine the bioactives, key targets, and potential pharmacological mechanism of FJHQD against AKI. MATERIALS AND METHODS The model of mouse renal ischemic reperfusion was adopted to verify the curative effect of FJHQD against renal injury. FJHQD was analyzed and separated by Ultra-High performance liquid chromatography (UHPLC). Bioactives and potential targets of FJHQD, as well as AKI-related targets, were retrieved from public databases. Crucial bioactive ingredients, potential targets, and signaling pathways were acquired through bioinformatics analysis, including protein-protein interaction (PPI), as well as the Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. Subsequently, molecular docking was carried out to predict the combination of active compounds with core targets. Besides, in vivo and vitro experiments were conducted to verify the findings. RESULTS A total of 20 bioactive ingredients of FJHQD (top 10 positive ion and negative ion compounds) and 274 FJHQD-AKI overlaped targets were screened. Bioinformatics analysis revealed that apoptosis mediated by PI3K-AKT signaling pathway might play an important role in FJHQD against AKI. Further experiments showed that FJHQD alleviated I/R-induced renal injury and OGD/R induced TEC apoptosis by activating PI3K-AKT signaling pathway. Moreover, molecular docking suggested (9Z,12Z,14E)-16-Hydroxy-9,12,14-octadecatrienoic acid, 2-Hydroxyacetophenone, Liquiritigenin, (S)-[10]-Gingerol and Isookanin-7-O-glucoside may be potential candidate agents, among which, PIK3CA interacted with Liquiritigenin, (S)-[10]-Gingerol, Isookanin-7-O-glucoside and 2-Hydroxyacetophenone respectively. AKT1 interacted with (9Z,12Z,14E)-16-Hydroxy-9,12,14-octadecatrienoic acid and 2-Hydroxyacetophenone. Cell experiments showed that the most important ingredient of FJHQD, Liquiritigenin, could inhibit the TEC apoptosis and up-regulate PI3K-Akt signaling pathway, which further confirmed the prediction by network pharmacology strategy and molecular docking. CONCLUSION Our results comprehensively illustrated the bioactives, potential targets, and molecular mechanism of FJHQD against AKI. It also provided a promising strategy to uncover the scientific basis and therapeutic mechanism of TCM formulae in treating diseases.
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Affiliation(s)
- Chengcheng Xiao
- Department of Urology, Qingdao Municipal Hospital, Qingdao, PR China
| | - Yayun Wang
- Department of Hematology, Qingdao Municipal Hospital, Qingdao, PR China
| | - Jingwei Liu
- Department of Urology, Qingdao Chengyang People's Hospital, Qingdao, PR China
| | - Xin Li
- Department of Anorectal, Affiliated Hospital of Qingdao University, Qingdao, PR China
| | - Peng Wang
- Department of Urology, Qingdao Municipal Hospital, Qingdao, PR China
| | - Junran Zhou
- Department of Thoracic Surgery, Qingdao Municipal Hospital, Qingdao, PR China
| | - Hao Xiu
- Department of Traditional Chinese Medicine, Qingdao Municipal Hospital, Qingdao, PR China
| | - Shun Lu
- Department of Traditional Chinese Medicine, Qingdao Municipal Hospital, Qingdao, PR China
| | - Hai Zhu
- Department of Urology, Qingdao Municipal Hospital, Qingdao, PR China
| | - Renhe Wang
- Department of Traditional Chinese Medicine, Qingdao Municipal Hospital, Qingdao, PR China.
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14
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Yu J, Lu Z, Chen B, He X, Zhao W, Cao H, Li Y, Peng G, Ou J, Ma Q, Yu L, Liu J. Liang-Ge-San protects against viral infection-induced acute lung injury through inhibiting α7nAChR-mediated mitophagy. PHYTOMEDICINE : INTERNATIONAL JOURNAL OF PHYTOTHERAPY AND PHYTOPHARMACOLOGY 2024; 135:156231. [PMID: 39566410 DOI: 10.1016/j.phymed.2024.156231] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/03/2024] [Revised: 10/21/2024] [Accepted: 11/05/2024] [Indexed: 11/22/2024]
Abstract
BACKGROUND Acute lung injury (ALI) is the main cause of death in clinical respiratory virus infection. Liang-Ge-San (LGS), a famous traditional Chinese formula, has been proved to be effective in treating ALI caused by lipopolysaccharide. However, the effects of LGS on ALI induced by viral infections remain uncertain. PURPOSE To investigate the effect and mechanism of action of LGS on viral infection-induced ALI. METHODS The inhibitory effects of LGS on virus-induced inflammation in vitro were evaluated by qRT-PCR and ELISA. The protein expression of α7nAChR was examined by Western blotting. α7nAChR was inhibited by the transfection of siRNA or methyllycaconitine citrate (MLA, an α7nAChR inhibitor) to investigate the role of α7nAChR in the anti-inflammatory effect of LGS. Adoptive culture and co-culture systems of macrophages RAW264.7 and alveolar epithelial cells MLE-12 were established to mimic their interaction. Western blotting, immunofluorescence, flow cytometry and transmission electron microscopy were used to examine the effects of LGS on mitophagy inhibition. In vivo, ALI mouse models induced by SARS-CoV-2, H1N1 or Poly(I:C) infection were established to explore the therapeutic effect and mechanism of LGS. RESULTS LGS reduced the release of IL-6, TNF-α and IL-1β and increased the expression of α7nAChR in virus-infected RAW264.7 cells. The blockage of α7nAChR counteracted the anti-inflammatory effect of LGS. Moreover, LGS significantly inhibited autophagy in MLE-12 cells induced by Poly(I:C) in adoptive culture and co-culture systems of RAW264.7 and MLE-12 cells, which could be attenuated after the inhibition of α7nAChR in RAW264.7 cells by decreasing the secretion of IL-6, TNF-α and IL-1β. Further study showed that LGS suppressed TNF-α-induced mitochondrial damage and mitophagy by inhibiting the generation of ROS in MLE-12 cells. In vivo, LGS significantly prolonged the survival time, alleviated pathological injury and acute inflammation of ALI mice induced by SARS-CoV-2, H1N1 or Poly(I:C) infection which were associated with the inhibition of α7nAChR-mediated mitophagy. CONCLUSION This study first demonstrates that LGS inhibits virus infection-induced inflammation in RAW246.7 cells by increasing the expression of α7nAChR, thereby inhibiting mitophagy induction in MLE-12 cells to alleviate ALI. This work indicates that LGS may serve as a candidate drug for treating ALI/ARDS caused by viral infection.
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Affiliation(s)
- Jingtao Yu
- Third Level Research Laboratory of State Administration of Traditional Chinese Medicine, School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, 510515, PR China; Guangdong Provincial Key Laboratory of Chinese Medicine Pharmaceutics, Guangzhou, 510515, PR China; Guangdong Basic Research Center of Excellence for Integrated Traditional and Western Medicine for Qingzhi Diseases, Guangzhou 510515, PR China
| | - Zibin Lu
- Third Level Research Laboratory of State Administration of Traditional Chinese Medicine, School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, 510515, PR China; Guangdong Provincial Key Laboratory of Chinese Medicine Pharmaceutics, Guangzhou, 510515, PR China; Guangdong Basic Research Center of Excellence for Integrated Traditional and Western Medicine for Qingzhi Diseases, Guangzhou 510515, PR China
| | - Bing Chen
- Third Level Research Laboratory of State Administration of Traditional Chinese Medicine, School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, 510515, PR China; Guangdong Provincial Key Laboratory of Chinese Medicine Pharmaceutics, Guangzhou, 510515, PR China; Guangdong Basic Research Center of Excellence for Integrated Traditional and Western Medicine for Qingzhi Diseases, Guangzhou 510515, PR China
| | - Xuemei He
- Third Level Research Laboratory of State Administration of Traditional Chinese Medicine, School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, 510515, PR China; Guangdong Provincial Key Laboratory of Chinese Medicine Pharmaceutics, Guangzhou, 510515, PR China; Guangdong Basic Research Center of Excellence for Integrated Traditional and Western Medicine for Qingzhi Diseases, Guangzhou 510515, PR China
| | - Wei Zhao
- Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University, Guangzhou 510515, PR China
| | - Huihui Cao
- Third Level Research Laboratory of State Administration of Traditional Chinese Medicine, School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, 510515, PR China; Guangdong Provincial Key Laboratory of Chinese Medicine Pharmaceutics, Guangzhou, 510515, PR China; Guangdong Basic Research Center of Excellence for Integrated Traditional and Western Medicine for Qingzhi Diseases, Guangzhou 510515, PR China
| | - Yuhua Li
- Third Level Research Laboratory of State Administration of Traditional Chinese Medicine, School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, 510515, PR China; Guangdong Provincial Key Laboratory of Chinese Medicine Pharmaceutics, Guangzhou, 510515, PR China; Guangdong Basic Research Center of Excellence for Integrated Traditional and Western Medicine for Qingzhi Diseases, Guangzhou 510515, PR China
| | - Gefei Peng
- Third Level Research Laboratory of State Administration of Traditional Chinese Medicine, School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, 510515, PR China; Guangdong Provincial Key Laboratory of Chinese Medicine Pharmaceutics, Guangzhou, 510515, PR China; Guangdong Basic Research Center of Excellence for Integrated Traditional and Western Medicine for Qingzhi Diseases, Guangzhou 510515, PR China
| | - Jinying Ou
- Third Level Research Laboratory of State Administration of Traditional Chinese Medicine, School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, 510515, PR China; Guangdong Provincial Key Laboratory of Chinese Medicine Pharmaceutics, Guangzhou, 510515, PR China; Guangdong Basic Research Center of Excellence for Integrated Traditional and Western Medicine for Qingzhi Diseases, Guangzhou 510515, PR China
| | - Qinhai Ma
- State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, 510182, PR China.
| | - Linzhong Yu
- Third Level Research Laboratory of State Administration of Traditional Chinese Medicine, School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, 510515, PR China; Guangdong Provincial Key Laboratory of Chinese Medicine Pharmaceutics, Guangzhou, 510515, PR China; Guangdong Basic Research Center of Excellence for Integrated Traditional and Western Medicine for Qingzhi Diseases, Guangzhou 510515, PR China.
| | - Junshan Liu
- Third Level Research Laboratory of State Administration of Traditional Chinese Medicine, School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, 510515, PR China; Guangdong Provincial Key Laboratory of Chinese Medicine Pharmaceutics, Guangzhou, 510515, PR China; Guangdong Basic Research Center of Excellence for Integrated Traditional and Western Medicine for Qingzhi Diseases, Guangzhou 510515, PR China.
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15
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Wang J, Zhu Z, Yang L, Nie Y, Liu S, Li D, Hou J, Wang R. Pharmacokinetics and tissue distribution of Yigong San in rats. JOURNAL OF ETHNOPHARMACOLOGY 2024; 331:118299. [PMID: 38729539 DOI: 10.1016/j.jep.2024.118299] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/02/2024] [Revised: 04/28/2024] [Accepted: 05/05/2024] [Indexed: 05/12/2024]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE In traditional Chinese medicine (TCM), Yigong San (YGS) is mainly used to treat dyspepsia caused by deficiency of spleen and stomach qi. Although the chemical composition and bioactivity of YGS has been well studied, the main in vivo compounds and their distribution in tissues still need to be made clearer. AIM OF THE STUDY To elucidate the pharmacokinetic profiles and tissue distribution of eight main compounds of YGS in rats, and provide a reference for clinical application and new drug development. MATERIALS AND METHODS UPLC-Q-Exactive-Orbitrap-MS was used to qualitatively characterize the parent compounds and their metabolites in the plasma of rats after oral administration of YGS. A sensitive, reliable, and accurate ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method using UPLC-AB Sciex QTRAP 5500 MS was established to quantitatively determine eight main compounds of YGS in rat plasma and tissues, including liquiritin, isoliquiritin, hesperidin, ginsenosides Rb1, Re and Rg1, atractylenolides I and II. RESULTS The mean area under the concentration-time curve (AUC) values of ginsenoside Rb1, hesperidin, and liquiritin at low, medium, and high doses were greater than 150 ng h/mL. The elimination half-life (t1/2) values of ginsenoside Rb1, atractylenolides I and II (low and medium doses) were longer than 10 h. Peak time (Tmax) values of all compounds were shorter than 10 h. Except for atractylenolides, the maximum concentration (Cmax) values of the compounds were greater than 10 ng/mL. The eight compounds were detected in the heart, brain, liver, spleen and kidney at 0.25 h after oral administration. Liquiritin and isoliquiritin had higher exposure in the liver and heart. Hesperidin and ginsenosides Rb1, Re, and Rg1 are mainly distributed in the spleen and kidney. Atractylenolides I and II are mainly distributed in spleen, liver and kidney. CONCLUSIONS All main compounds of YGS, i.e., liquiritin, isoliquiritin, hesperidin, ginsenosides Rb1, Re, and Rg1, and atractylenolides I and II are absorbed into plasma and widely distributed in various tissues. Among them, hesperidin, ginsenoside Rb1, and atractylenolide I are main in vivo compounds. They are mainly distributed in spleen, liver and kidney. The results of this study provide a basis for further in-depth development and application of YGS.
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Affiliation(s)
- Jing Wang
- School of Life Sciences, Beijing University of Chinese Medicine, Liangxiang University Town, Yangguang South Street, Fangshan District, Beijing, 102488, China
| | - Zhihao Zhu
- School of Life Sciences, Beijing University of Chinese Medicine, Liangxiang University Town, Yangguang South Street, Fangshan District, Beijing, 102488, China
| | - Lan Yang
- School of Life Sciences, Beijing University of Chinese Medicine, Liangxiang University Town, Yangguang South Street, Fangshan District, Beijing, 102488, China
| | - Yudi Nie
- School of Life Sciences, Beijing University of Chinese Medicine, Liangxiang University Town, Yangguang South Street, Fangshan District, Beijing, 102488, China
| | - Siqi Liu
- School of Life Sciences, Beijing University of Chinese Medicine, Liangxiang University Town, Yangguang South Street, Fangshan District, Beijing, 102488, China
| | - Dan Li
- Hebei Shineway Pharmaceutical Co., Ltd., Yingbin Street, Langfang, Hebei, 065201, China.
| | - Jincai Hou
- Hebei Shineway Pharmaceutical Co., Ltd., Yingbin Street, Langfang, Hebei, 065201, China.
| | - Rufeng Wang
- School of Life Sciences, Beijing University of Chinese Medicine, Liangxiang University Town, Yangguang South Street, Fangshan District, Beijing, 102488, China.
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16
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He X, Zhang Z, Hu M, Lin X, Weng X, Lu J, Fang L, Chen X. Liquiritin Alleviates Inflammation in Lipopolysaccharide-Induced Human Corneal Epithelial Cells. Curr Eye Res 2024; 49:930-941. [PMID: 38767463 DOI: 10.1080/02713683.2024.2353263] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/02/2024] [Revised: 04/09/2024] [Accepted: 05/04/2024] [Indexed: 05/22/2024]
Abstract
PURPOSE This research was designed to elucidate the anti-inflammatory impacts of liquiritin on lipopolysaccharide (LPS)-activated human corneal epithelial cells (HCECs). METHODS The Cell Counting kit-8 (CCK-8) assay was adopted to assess cell viability. The enzyme-linked immunosorbent assay (ELISA) was used to detect the secretion levels of the proinflammatory cytokines IL-6, IL-8, and TNF-α. Transcriptome analysis was conducted to identify the genes that exhibited differential expression between different treatment. The model group included cells treated with LPS (10 µg/mL), the treatment group comprised cells treated with liquiritin (80 µM) and LPS (10 µg/mL), and the control group consisted of untreated cells. To further validate the expression levels of the selected genes, including CSF2, CXCL1, CXCL2, CXCL8, IL1A, IL1B, IL24, IL6, and LTB, quantitative real-time PCR was performed. The expression of proteins related to the Akt/NF-κB signaling pathway was assessed through western blot analysis. NF-κB nuclear translocation was evaluated through immunofluorescence staining. RESULTS The secretion of IL-6, IL-8, and TNF-α in LPS-induced HCECs was significantly downregulated by liquiritin. Based on the transcriptome analysis, the mRNA expression of pro-inflammatory cytokines, namely IL-6, IL-8, IL-1β, IL-24, TNF-α, and IL-1α was overproduced by LPS stimulation, and suppressed after liquiritin treatment. Furthermore, the Western blot results revealed a remarkable reduction in the phosphorylation degrees of NF-κB p65, IκB, and Akt upon treatment with liquiritin. Additionally, immunofluorescence analysis confirmed liquiritin's inhibition of LPS-induced p65 nuclear translocation. CONCLUSIONS Collectively, these findings imply that liquiritin suppresses the expression of proinflammatory cytokines, and the anti-inflammatory impacts of liquiritin may be caused by its repression of the Akt/NF-κB signaling pathway in LPS-induced HCECs. These data indicate that liquiritin could provide a potential therapeutic application for inflammation-associated corneal diseases.
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Affiliation(s)
- Xian He
- Zhejiang Institute of Medical Device Supervision and Testing, Hangzhou, Zhejiang Province, China
- Key Laboratory of Safety Evaluation of Medical Devices of Zhejiang Province, Hangzhou, Zhejiang Province, China
| | - Ziyang Zhang
- Zhejiang Institute of Medical Device Supervision and Testing, Hangzhou, Zhejiang Province, China
| | - Meili Hu
- Zhejiang Institute of Medical Device Supervision and Testing, Hangzhou, Zhejiang Province, China
| | - Xinyi Lin
- Zhejiang Institute of Medical Device Supervision and Testing, Hangzhou, Zhejiang Province, China
| | - Xu Weng
- Zhejiang Institute of Medical Device Supervision and Testing, Hangzhou, Zhejiang Province, China
| | - Jiajun Lu
- Zhejiang Institute of Medical Device Supervision and Testing, Hangzhou, Zhejiang Province, China
| | - Li Fang
- Zhejiang Institute of Medical Device Supervision and Testing, Hangzhou, Zhejiang Province, China
- Key Laboratory of Safety Evaluation of Medical Devices of Zhejiang Province, Hangzhou, Zhejiang Province, China
| | - Xianhua Chen
- Zhejiang Institute of Medical Device Supervision and Testing, Hangzhou, Zhejiang Province, China
- Key Laboratory of Safety Evaluation of Medical Devices of Zhejiang Province, Hangzhou, Zhejiang Province, China
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Chen J, Li J, Wang F, Ge R, Wang L, Huang J. Metabolite profiling of liquiritin in acute myocardial infarction model rat after intragastric administration using an information-dependent acquisition-mediated ultra-high-performance liquid chromatography-tandem mass spectrometry method. Biomed Chromatogr 2024; 38:e5933. [PMID: 38863152 DOI: 10.1002/bmc.5933] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/04/2023] [Revised: 04/03/2024] [Accepted: 04/09/2024] [Indexed: 06/13/2024]
Abstract
Liquiritin (LQ), a kind of flavonoid isolated from licorice, was proven to have great potential in treating heart failure. Pharmacokinetic evaluation is important for demonstrating clinical efficacy and mechanisms, and the prototype drug and its metabolite profiling are important for drug discovery and development. However, the metabolism of LQ in acute myocardial infarction (AMI) model rats still needs to be studied in depth. An information-dependent acquisition (IDA)-ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method was applied to profile LQ metabolites in AMI model rat plasma. Protein precipitation and extraction were used for sample preparation. Chromatographic separation was achieved using an XSelect BEH C18 column (2.1 × 150 mm, 2.5 μm) using gradient elution method combining 0.1% formic acid and acetonitrile with a flow rate of 0.3 mL/min. Twelve metabolites were identified in IDA mode, sulfation, glucuronidation, methylation, methyl esterification, glutamine conjugation, and valine conjugation, and their composite reactions were presumed as the primary pathways of LQ metabolism. The variation in the peak areas showed that the time to reach the peak drug concentration of LQ and 12 metabolites was within 5 h. In summary, IDA-bridged UHPLC-MS/MS from characteristic fragment ions toward confidence-enhanced identification could effectively screen and profile metabolites.
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Affiliation(s)
- Jian Chen
- School of Integrated Chinese and Western Medicine, Anhui University of Chinese Medicine, Hefei, China
- Institute of Integrated Chinese and Western Medicine, Anhui Academy of Chinese Medicine, Hefei, China
- Anhui Province Key Laboratory of Chinese Medicinal Formula, Hefei, China
| | - Jing Li
- School of Integrated Chinese and Western Medicine, Anhui University of Chinese Medicine, Hefei, China
- Institute of Integrated Chinese and Western Medicine, Anhui Academy of Chinese Medicine, Hefei, China
| | - Feng Wang
- School of Integrated Chinese and Western Medicine, Anhui University of Chinese Medicine, Hefei, China
- Institute of Integrated Chinese and Western Medicine, Anhui Academy of Chinese Medicine, Hefei, China
| | - Ruirui Ge
- School of Integrated Chinese and Western Medicine, Anhui University of Chinese Medicine, Hefei, China
- Institute of Integrated Chinese and Western Medicine, Anhui Academy of Chinese Medicine, Hefei, China
| | - Liang Wang
- School of Integrated Chinese and Western Medicine, Anhui University of Chinese Medicine, Hefei, China
- Institute of Integrated Chinese and Western Medicine, Anhui Academy of Chinese Medicine, Hefei, China
| | - Jinling Huang
- School of Integrated Chinese and Western Medicine, Anhui University of Chinese Medicine, Hefei, China
- Institute of Integrated Chinese and Western Medicine, Anhui Academy of Chinese Medicine, Hefei, China
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18
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Zhang Y, Li S, Huang Y, Song C, Chen W, Yang Y. Therapeutic Effect of Liquiritin Carbomer Gel on Topical Glucocorticoid-Induced Skin Inflammation in Mice. Pharmaceutics 2024; 16:1001. [PMID: 39204346 PMCID: PMC11359290 DOI: 10.3390/pharmaceutics16081001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2024] [Revised: 07/25/2024] [Accepted: 07/27/2024] [Indexed: 09/04/2024] Open
Abstract
Glucocorticoids are often used and highly effective anti-inflammatory medications, but prolonged topical application may alter the epidermis' normal structure and function, potentially resulting in a number of adverse effects. Topical glucocorticoid-induced skin inflammation is a dangerous condition that develops after topical glucocorticoid use. The patients become dependent on the medication and, even after the medication is stopped, the dermatitis symptoms recur, severely impairing their quality of life. Thus, the need to aggressively confront Topical glucocorticoid-induced skin inflammation is critical. Prior research has demonstrated that topical administration of licorice's flavonoid component liquiritin stimulates epidermal proliferation, which in turn enhances the creation of collagen and the healing of wounds. Therefore, the purpose of this work was to determine if topical use of liquiritin carbomer gel can treat glucocorticoid-induced changes in mice skin epidermal function, and the mechanisms involved. The findings demonstrated that, in the mice model of topical glucocorticoid-induced skin inflammation, liquiritin carbomer gel aided in the restoration of skin barrier function. These outcomes may have been caused by enhanced expression of the proteins Aquaporin 3, Keratin 10, and Claudin-1, as well as the restoration of epidermal hyaluronan content. In the meantime, liquiritin carbomer gel dramatically decreased the expression of TNF-α, IL-1β, IL-6, IFN-γ, and IgE in mice, according to ELISA tests. Furthermore, topical treatment of liquiritin carbomer gel boosted the expression of superoxide dismutase, catalase, and decreased malondialdehyde expression, potentially counteracting the detrimental effects of glucocorticoids on the epidermis. In summary, these findings imply that topical liquiritin carbomer gel can treat glucocorticoid-induced skin damage through various mechanisms of action.
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Affiliation(s)
- Yun Zhang
- School of Nursing, Guangdong Pharmaceutical University, Guangzhou 510006, China
| | - Sijia Li
- School of Nursing, Guangdong Pharmaceutical University, Guangzhou 510006, China
| | - Yanfang Huang
- School of Nursing, Guangdong Pharmaceutical University, Guangzhou 510006, China
| | - Congjing Song
- School of Nursing, Guangdong Pharmaceutical University, Guangzhou 510006, China
| | - Weiqiang Chen
- School of Basic Medical Sciences, Guangdong Pharmaceutical University, Guangzhou 510006, China
| | - Yiling Yang
- School of Nursing, Guangdong Pharmaceutical University, Guangzhou 510006, China
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Cai J, Tan X, Hu Q, Pan H, Zhao M, Guo C, Zeng J, Ma X, Zhao Y. Flavonoids and Gastric Cancer Therapy: From Signaling Pathway to Therapeutic Significance. Drug Des Devel Ther 2024; 18:3233-3253. [PMID: 39081701 PMCID: PMC11287762 DOI: 10.2147/dddt.s466470] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2024] [Accepted: 07/01/2024] [Indexed: 08/02/2024] Open
Abstract
Gastric cancer (GC) is a prevalent gastrointestinal tumor characterized by high mortality and recurrence rates. Current treatments often have limitations, prompting researchers to explore novel anti-tumor substances and develop new drugs. Flavonoids, natural compounds with diverse biological activities, are gaining increasing attention in this regard. We searched from PubMed, Web of Science, SpringerLink and other databases to find the relevant literature in the last two decades. Using "gastric cancer", "stomach cancers", "flavonoid", "bioflavonoid", "2-Phenyl-Chromene" as keywords, were searched, then analyzed and summarized the mechanism of flavonoids in the treatment of GC. It was revealed that the anti-tumor mechanism of flavonoids involves inhibiting tumor growth, proliferation, invasion, and metastasis, as well as inducing cell death through various processes such as apoptosis, autophagy, ferroptosis, and pyroptosis. Additionally, combining flavonoids with other chemotherapeutic agents like 5-FU and platinum compounds can potentially reduce chemoresistance. Flavonoids have also demonstrated enhanced biological activity when used in combination with other natural products. Consequently, this review proposes innovative perspectives for the development of flavonoids as new anti-GC agents.
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Affiliation(s)
- Jiaying Cai
- School of Clinical Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, People’s Republic of China
| | - Xiyue Tan
- State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, People’s Republic of China
| | - Qichao Hu
- State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, People’s Republic of China
| | - Huafeng Pan
- Science and Technology Innovation Center, Guangzhou University of Chinese Medicine, Guangzhou, People’s Republic of China
| | - Maoyuan Zhao
- TCM Regulating Metabolic Diseases Key Laboratory of Sichuan Province, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, People’s Republic of China
| | - Cui Guo
- TCM Regulating Metabolic Diseases Key Laboratory of Sichuan Province, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, People’s Republic of China
| | - Jinhao Zeng
- School of Clinical Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, People’s Republic of China
- TCM Regulating Metabolic Diseases Key Laboratory of Sichuan Province, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, People’s Republic of China
- Department of Gastroenterology, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, People’s Republic of China
| | - Xiao Ma
- State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, People’s Republic of China
| | - Yanling Zhao
- Department of Pharmacy, Chinese PLA General Hospital, Beijing, People’s Republic of China
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Chu Y, Zhang X, Zuo L, Wang X, Shi Y, Liu L, Zhou L, Kang J, Li B, Cheng W, Du S, Sun Z. Establishment of a multi-strategy platform for quality control and quality markers screen of Mailuoshutong pill. J Pharm Biomed Anal 2024; 243:116070. [PMID: 38428246 DOI: 10.1016/j.jpba.2024.116070] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/08/2024] [Revised: 02/21/2024] [Accepted: 02/22/2024] [Indexed: 03/03/2024]
Abstract
Thromboangiitis obliterans (TAO) is a non-atherosclerotic segmental inflammatory occlusive disease with a high recurrence rate, high disability rate, difficulty to cure, and poor prognosis. It has been clinically proven that Mailuoshutong pill (MLSTP) is an effective traditional Chinese medicine for treating TAO. As MLSTP contains hundreds of chemical components, the quality control of which is a challenge in the development of reliable quality evaluation metrics. This study aimed to evaluate the quality uniformity of MLSTP by establishing a multi-strategy platform. In the present study, the key targets and signaling pathways of MLSTP treating TAO were predicted by network pharmacology. It was further shown by in vivo validation experiments that MLSTP exerted therapeutic effects on TAO by modulating the PI3K-AKT signaling pathway, VEGF signaling pathway, and HIF-1 signaling pathway. In addition, UPLC fingerprints of MLSTP were established and screened for potential Q-markers of MLSTP in combination with network pharmacology results. Six components, including chlorogenic acid, liquiritin, paeoniflorin, calycosin-7-glucoside, berberine, and formononetin, were selected as potential quality markers (Q-markers) in MLSTP. Finally, the quantitative analysis of multi-components by single marker (QAMS) method was established to quantitatively analyze the six potential Q-markers, and the results were consistent with those obtained by the external standard method (ESM). Taken together, the multi-strategy platform established in this study would be conducive to the Q-markers screening and quality control of MLSTP, improving the quality standard of MLSTP and providing favorable assurance for the clinical management of TAO.
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Affiliation(s)
- Yaojuan Chu
- Department of Pharmacy, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China; Henan Engineering Research Center of Clinical Mass Spectrometry for Precision Medicine, Zhengzhou Key Laboratory of Clinical Mass Spectrometry, Zhengzhou 450052, China
| | - Xiangyu Zhang
- Department of Pharmacy, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China; Henan Engineering Research Center of Clinical Mass Spectrometry for Precision Medicine, Zhengzhou Key Laboratory of Clinical Mass Spectrometry, Zhengzhou 450052, China; Department of Pharmacy, the Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China
| | - Lihua Zuo
- Department of Pharmacy, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China; Henan Engineering Research Center of Clinical Mass Spectrometry for Precision Medicine, Zhengzhou Key Laboratory of Clinical Mass Spectrometry, Zhengzhou 450052, China
| | - Xiaobao Wang
- Department of Pharmacy, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China; Henan Engineering Research Center of Clinical Mass Spectrometry for Precision Medicine, Zhengzhou Key Laboratory of Clinical Mass Spectrometry, Zhengzhou 450052, China
| | - Yingying Shi
- Department of Pharmacy, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China; Henan Engineering Research Center of Clinical Mass Spectrometry for Precision Medicine, Zhengzhou Key Laboratory of Clinical Mass Spectrometry, Zhengzhou 450052, China
| | - Liwei Liu
- Department of Pharmacy, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China; Henan Engineering Research Center of Clinical Mass Spectrometry for Precision Medicine, Zhengzhou Key Laboratory of Clinical Mass Spectrometry, Zhengzhou 450052, China
| | - Lin Zhou
- Department of Pharmacy, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China; Henan Engineering Research Center of Clinical Mass Spectrometry for Precision Medicine, Zhengzhou Key Laboratory of Clinical Mass Spectrometry, Zhengzhou 450052, China
| | - Jian Kang
- Department of Pharmacy, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China; Henan Engineering Research Center of Clinical Mass Spectrometry for Precision Medicine, Zhengzhou Key Laboratory of Clinical Mass Spectrometry, Zhengzhou 450052, China
| | - Bing Li
- State Key Laboratory of Common Technology of Traditional Chinese Medicine and Pharmaceuticals, Lunan Pharmaceutical Group Co., Ltd., Linyi 276000, China
| | - Wenbo Cheng
- Suzhou Institute of Biomedical Engineering and Technology, Chinese Academy of Sciences, Suzhou 215000, China
| | - Shuzhang Du
- Department of Pharmacy, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China; Henan Engineering Research Center of Clinical Mass Spectrometry for Precision Medicine, Zhengzhou Key Laboratory of Clinical Mass Spectrometry, Zhengzhou 450052, China.
| | - Zhi Sun
- Department of Pharmacy, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China; Henan Engineering Research Center of Clinical Mass Spectrometry for Precision Medicine, Zhengzhou Key Laboratory of Clinical Mass Spectrometry, Zhengzhou 450052, China.
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Lee YG, Jung Y, Choi HK, Lee JI, Lim TG, Lee J. Natural Product-Derived Compounds Targeting Keratinocytes and Molecular Pathways in Psoriasis Therapeutics. Int J Mol Sci 2024; 25:6068. [PMID: 38892253 PMCID: PMC11172960 DOI: 10.3390/ijms25116068] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/17/2024] [Revised: 05/28/2024] [Accepted: 05/29/2024] [Indexed: 06/21/2024] Open
Abstract
Psoriasis is a chronic autoimmune inflammatory skin disorder that affects approximately 2-3% of the global population due to significant genetic predisposition. It is characterized by an uncontrolled growth and differentiation of keratinocytes, leading to the formation of scaly erythematous plaques. Psoriasis extends beyond dermatological manifestations to impact joints and nails and is often associated with systemic disorders. Although traditional treatments provide relief, their use is limited by potential side effects and the chronic nature of the disease. This review aims to discuss the therapeutic potential of keratinocyte-targeting natural products in psoriasis and highlight their efficacy and safety in comparison with conventional treatments. This review comprehensively examines psoriasis pathogenesis within keratinocytes and the various related signaling pathways (such as JAK-STAT and NF-κB) and cytokines. It presents molecular targets such as high-mobility group box-1 (HMGB1), dual-specificity phosphatase-1 (DUSP1), and the aryl hydrocarbon receptor (AhR) for treating psoriasis. It evaluates the ability of natural compounds such as luteolin, piperine, and glycyrrhizin to modulate psoriasis-related pathways. Finally, it offers insights into alternative and sustainable treatment options with fewer side effects.
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Affiliation(s)
- Yu Geon Lee
- Division of Food Functionality Research, Korea Food Research Institute, Wanju-gun 55365, Republic of Korea; (Y.G.L.); (Y.J.); (H.-K.C.); (J.-I.L.)
| | - Younjung Jung
- Division of Food Functionality Research, Korea Food Research Institute, Wanju-gun 55365, Republic of Korea; (Y.G.L.); (Y.J.); (H.-K.C.); (J.-I.L.)
| | - Hyo-Kyoung Choi
- Division of Food Functionality Research, Korea Food Research Institute, Wanju-gun 55365, Republic of Korea; (Y.G.L.); (Y.J.); (H.-K.C.); (J.-I.L.)
| | - Jae-In Lee
- Division of Food Functionality Research, Korea Food Research Institute, Wanju-gun 55365, Republic of Korea; (Y.G.L.); (Y.J.); (H.-K.C.); (J.-I.L.)
| | - Tae-Gyu Lim
- Department of Food Science & Biotechnology, College of Life Sciences, Sejong University, Seoul 05006, Republic of Korea;
- Carbohydrate Bioproduct Research Center, Department of Food Science & Biotechnology, Sejong University, Seoul 05006, Republic of Korea
| | - Jangho Lee
- Division of Food Functionality Research, Korea Food Research Institute, Wanju-gun 55365, Republic of Korea; (Y.G.L.); (Y.J.); (H.-K.C.); (J.-I.L.)
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Gao C, Song XD, Chen FH, Wei GL, Guo CY. The protective effect of natural medicines in rheumatoid arthritis via inhibit angiogenesis. Front Pharmacol 2024; 15:1380098. [PMID: 38881875 PMCID: PMC11176484 DOI: 10.3389/fphar.2024.1380098] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2024] [Accepted: 05/10/2024] [Indexed: 06/18/2024] Open
Abstract
Rheumatoid arthritis is a chronic immunological disease leading to the progressive bone and joint destruction. Angiogenesis, accompanied by synovial hyperplasia and inflammation underlies joint destruction. Delaying or even blocking synovial angiogenesis has emerged as an important target of RA treatment. Natural medicines has a long history of treating RA, and numerous reports have suggested that natural medicines have a strong inhibitory activity on synovial angiogenesis, thereby improving the progression of RA. Natural medicines could regulate the following signaling pathways: HIF/VEGF/ANG, PI3K/Akt pathway, MAPKs pathway, NF-κB pathway, PPARγ pathway, JAK2/STAT3 pathway, etc., thereby inhibiting angiogenesis. Tripterygium wilfordii Hook. f. (TwHF), sinomenine, and total glucoside of Paeonia lactiflora Pall. Are currently the most representative of all natural products worthy of development and utilization. In this paper, the main factors affecting angiogenesis were discussed and different types of natural medicines that inhibit angiogenesis were systematically summarized. Their specific anti-angiogenesis mechanisms are also reviewed which aiming to provide new perspective and options for the management of RA by targeting angiogenesis.
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Affiliation(s)
- Chang Gao
- Department of Pharmacy, First Affiliated Hospital of Gannan Medical University, Jiangxi, Ganzhou, China
| | - Xiao-Di Song
- Gannan Medical University, Jiangxi, Ganzhou, China
| | - Fang-Hui Chen
- Department of Pharmacy, First Affiliated Hospital of Gannan Medical University, Jiangxi, Ganzhou, China
| | - Gui-Lin Wei
- Department of Pharmacy, First Affiliated Hospital of Gannan Medical University, Jiangxi, Ganzhou, China
| | - Chun-Yu Guo
- Department of Pharmacy, First Affiliated Hospital of Gannan Medical University, Jiangxi, Ganzhou, China
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Jia Z, Zhang J, Yang X, Chen H, Wang Y, Francis OB, Li Y, Liu Z, Zhang S, Wang Q. Bioactive components and potential mechanisms of Biqi Capsule in the treatment of osteoarthritis: based on chondroprotective and anti-inflammatory activity. Front Pharmacol 2024; 15:1347970. [PMID: 38694911 PMCID: PMC11061359 DOI: 10.3389/fphar.2024.1347970] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2023] [Accepted: 04/01/2024] [Indexed: 05/04/2024] Open
Abstract
Cartilage damage and synovial inflammation are vital pathological changes in osteoarthritis (OA). Biqi Capsule, a traditional Chinese medicine formula used for the clinical treatment of arthritis in China, yields advantages in attenuating OA progression. The drawback here is that the bioactive components and pharmacological mechanisms by which Biqi Capsule exerts its anti-inflammatory and chondroprotective effects have yet to be fully clarified. For in vivo studies, a papain-induced OA rat model was established to explore the pharmacological effects and potential mechanisms of Biqi Capsule against OA. Biqi Capsule alleviated articular cartilage degeneration and chondrocyte damage in OA rats and inhibited the phosphorylation of NF-κB and the expression of pro-inflammatory cytokines in synovial tissue. Network pharmacology analysis suggested that the primary biological processes regulated by Biqi Capsule are inflammation and oxidative stress, and the critical pathway regulated is the PI3K/AKT signaling pathway. The result of this analysis was later verified on SW1353 cells. The in vitro studies demonstrated that Glycyrrhizic Acid and Liquiritin in Biqi Capsule attenuated H2O2-stimulated SW1353 chondrocyte damage via activation of PI3K/AKT/mTOR pathway. Moreover, Biqi Capsule alleviated inflammatory responses in LPS-stimulated RAW264.7 macrophages via the NF-κB/IL-6 pathway. These observations were suggested to have been facilitated by Brucine, Liquiritin, Salvianolic Acid B, Glycyrrhizic Acid, Cryptotanshinone, and Tanshinone ⅡA. Put together, this study partially clarifies the pharmacological mechanisms and the bioactive components of Biqi capsules against OA and suggests that it is a promising therapeutic option for the treatment of OA. Chemical compounds studied in this article. Strychnine (Pubchem CID:441071); Brucine (Pubchem CID:442021); Liquiritin (Pubchem CID:503737); Salvianolic Acid B (Pubchem CID:6451084); Glycyrrhizic Acid (Pubchem CID:14982); Cryptotanshinone (Pubchem CID:160254); Tanshinone ⅡA (Pubchem CID:164676).
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Affiliation(s)
- Ziyue Jia
- School of Chinese Materia Medica, Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Jiale Zhang
- Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Xintong Yang
- Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Huiyou Chen
- School of Chinese Materia Medica, Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Yuxing Wang
- School of Chinese Materia Medica, Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Opoku Bonsu Francis
- Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Yuanchao Li
- School of Chinese Materia Medica, Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Zhanbiao Liu
- Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Shaozhuo Zhang
- School of Chinese Materia Medica, Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Qilong Wang
- Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China
- State Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China
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Qiu M, Cheng L, Xu J, Jin M, Yuan W, Ge Q, Zou K, Chen J, Huang Y, Li J, Zhu L, Xu B, Zhang C, Jin H, Wang P. Liquiritin reduces chondrocyte apoptosis through P53/PUMA signaling pathway to alleviate osteoarthritis. Life Sci 2024; 343:122536. [PMID: 38423170 DOI: 10.1016/j.lfs.2024.122536] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2023] [Revised: 02/08/2024] [Accepted: 02/23/2024] [Indexed: 03/02/2024]
Abstract
AIMS The main pathological features of osteoarthritis (OA) include the degeneration of articular cartilage and a decrease in matrix synthesis. Chondrocytes, which contribute to matrix synthesis, play a crucial role in the development of OA. Liquiritin, an effective ingredient extracted from Glycyrrhiza uralensis Fisch., has been used for over 1000 years to treat OA. This study aims to investigate the impact of liquiritin on OA and its underlying mechanism. MATERIALS AND METHODS Gait and hot plate tests assessed mouse behavior, while Micro-CT and ABH/OG staining observed joint morphological changes. The TUNEL kit detected chondrocyte apoptosis. Western blot and immunofluorescence techniques determined the expression levels of cartilage metabolism markers COL2 and MMP13, as well as apoptosis markers caspase3, bcl2, P53, and PUMA. KEGG analysis and molecular docking technology were used to verify the relationship between liquiritin and P53. KEY FINDINGS Liquiritin alleviated pain sensitivity and improved gait impairment in OA mice. Additionally, we found that liquiritin could increase COL2 levels and decrease MMP13 levels both in vivo and in vitro. Importantly, liquiritin reduced chondrocyte apoptosis induced by OA, through decreased expression of caspase3 expression and increased expression of bcl2 expression. Molecular docking revealed a strong binding affinity between liquiritin and P53. Both in vivo and in vitro studies demonstrated that liquiritin suppressed the expression of P53 and PUMA in cartilage. SIGNIFICANCE This indicated that liquiritin may alleviate OA progression by inhibiting the P53/PUMA signaling pathway, suggesting that liquiritin is a potential strategy for the treatment of OA.
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Affiliation(s)
- Min Qiu
- Institute of Orthopedics and Traumatology, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Hangzhou, China; College of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, China
| | - Liangyan Cheng
- Institute of Orthopedics and Traumatology, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Hangzhou, China; College of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, China
| | - Jianbo Xu
- Institute of Orthopedics and Traumatology, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Hangzhou, China; The First People's Hospital of Xiaoshan District, Xiaoshan Affiliated Hospital of Wenzhou Medical University, Hangzhou, China
| | - Minwei Jin
- Department of the Orthopedic Surgery, the Second Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, China
| | - Wenhua Yuan
- Institute of Orthopedics and Traumatology, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Hangzhou, China; The First College of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, China
| | - Qinwen Ge
- Institute of Orthopedics and Traumatology, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Hangzhou, China; The First College of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, China
| | - Kaiao Zou
- Institute of Orthopedics and Traumatology, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Hangzhou, China; The First College of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, China
| | - Jiali Chen
- Institute of Orthopedics and Traumatology, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Hangzhou, China; The First College of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, China
| | - Yuliang Huang
- Department of the Orthopedic Surgery, the Second Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, China
| | - Ju Li
- Institute of Orthopedics and Traumatology, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Hangzhou, China
| | - Liming Zhu
- The First People's Hospital of Xiaoshan District, Xiaoshan Affiliated Hospital of Wenzhou Medical University, Hangzhou, China
| | - Bing Xu
- Wenzhou Hospital of Integrated Traditional Chinese and Western Medicine, Wenzhou, China
| | - Chunchun Zhang
- Institute of Orthopedics and Traumatology, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Hangzhou, China; College of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, China.
| | - Hongting Jin
- Institute of Orthopedics and Traumatology, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Hangzhou, China; The First College of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, China.
| | - Pinger Wang
- Institute of Orthopedics and Traumatology, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Hangzhou, China; The First College of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, China.
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Chen X, Wu H, Li P, Peng W, Wang Y, Zhang X, Zhang A, Li J, Meng F, Wang W, Su W. Unraveling the Mechanism of Xiaochaihu Granules in Alleviating Yeast-Induced Fever Based on Network Analysis and Experimental Validation. Pharmaceuticals (Basel) 2024; 17:475. [PMID: 38675434 PMCID: PMC11053540 DOI: 10.3390/ph17040475] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/12/2024] [Revised: 03/30/2024] [Accepted: 04/06/2024] [Indexed: 04/28/2024] Open
Abstract
Xiaochaihu granules (XCHG) are extensively used to treat fever. Nevertheless, the underlying mechanism remains elusive. This study aimed to explore the potential of XCHG in mitigating yeast-induced fever and the underlying metabolic pathways. The chemical composition of XCHG was ascertained using ultra-fast liquid chromatography/quadrupole-time-of-flight tandem mass spectrometry (UFLC-Q-TOF-MS/MS), followed by integrated network analysis to predict potential targets. We then conducted experimental validation using pharmacological assays and metabolomics analysis in a yeast-induced mouse fever model. The study identified 133 compounds in XCHG, resulting in the development of a comprehensive network of herb-compound-biological functional modules. Subsequently, molecular dynamic (MD) simulations confirmed the stability of the complexes, including γ-aminobutyric acid B receptor 2 (GABBR2)-saikosaponin C, prostaglandin endoperoxide synthases (PTGS2)-lobetyolin, and NF-κB inhibitor IκBα (NFKBIA)-glycyrrhizic acid. Animal experiments demonstrated that XCHG reduced yeast-induced elevation in NFKBIA's downstream regulators [interleukin (IL)-1β and IL-8], inhibited PTGS2 activity, and consequently decreased prostaglandin E2 (PGE2) levels. XCHG also downregulated the levels of 5-hydroxytryptamine (5-HT), γ-aminobutyric acid (GABA), corticotropin releasing hormone (CRH), and adrenocorticotrophin (ACTH). These corroborated the network analysis results indicating XCHG's effectiveness against fever in targeting NFKBIA, PTGS2, and GABBR2. The hypothalamus metabolomics analysis identified 14 distinct metabolites as potential antipyretic biomarkers of XCHG. In conclusion, our findings suggest that XCHG alleviates yeast-induced fever by regulating inflammation/immune responses, neuromodulation, and metabolism modules, providing a scientific basis for the anti-inflammatory and antipyretic properties of XCHG.
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Affiliation(s)
| | | | | | | | | | | | | | | | | | | | - Weiwei Su
- Guangdong Engineering & Technology Research Center for Quality and Efficacy Reevaluation of Post-Market Traditional Chinese Medicine, Guangdong Provincial Key Laboratory of Plant Resources, State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou 510275, China
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Eltahir AOE, Lategan KL, David OM, Pool EJ, Luckay RC, Hussein AA. Green Synthesis of Gold Nanoparticles Using Liquiritin and Other Phenolics from Glycyrrhiza glabra and Their Anti-Inflammatory Activity. J Funct Biomater 2024; 15:95. [PMID: 38667552 PMCID: PMC11051159 DOI: 10.3390/jfb15040095] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2024] [Revised: 03/29/2024] [Accepted: 04/02/2024] [Indexed: 04/28/2024] Open
Abstract
Phenolic compounds are the main phytochemical constituents of many higher plants. They play an important role in synthesizing metal nanoparticles using green technology due to their ability to reduce metal salts and stabilize them through physical interaction/conjugation to the metal surface. Six pure phenolic compounds were isolated from licorice (Glycyrrhiza glabra) and employed in synthesizing gold nanoparticles (AuNPs). The isolated compounds were identified as liquiritin (1), isoliquiritin (2), neoisoliquiritin (3), isoliquiritin apioside (4), liquiritin apioside (5), and glabridin (6). The synthesized AuNPs were characterized using UV, zeta sizer, HRTEM, and IR and tested for their stability in different biological media. The phenolic isolates and their corresponding synthesized NP conjugates were tested for their potential in vitro cytotoxicity. The anti-inflammatory effects were investigated in both normal and inflammation-induced settings, where inflammatory biomarkers were stimulated using lipopolysaccharides (LPSs) in the RAW 264.7 macrophage cell line. LPS, functioning as a mitogen, promotes cell growth by reducing apoptosis, potentially contributing to observed outcomes. Results indicated that all six pure phenolic isolates inhibited cell proliferation. The AuNP conjugates of all the phenolic isolates, except liquiritin apioside (5), inhibited cell viability. LPS initiates inflammatory markers by binding to cell receptors and setting off a cascade of events leading to inflammation. All the pure phenolic isolates, except isoliquiritin, neoisoliquiritin, and isoliquiritin apioside inhibited the inflammatory activity of RAW cells in vitro.
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Affiliation(s)
- Ali O. E. Eltahir
- Chemistry Department, Cape Peninsula University of Technology, Bellville 7535, South Africa;
| | - Kim L. Lategan
- Department of Medical Bioscience, University of Western the Cape, Bellville 7535, South Africa; (K.L.L.); (O.M.D.); (E.J.P.)
| | - Oladipupo M. David
- Department of Medical Bioscience, University of Western the Cape, Bellville 7535, South Africa; (K.L.L.); (O.M.D.); (E.J.P.)
| | - Edmund J. Pool
- Department of Medical Bioscience, University of Western the Cape, Bellville 7535, South Africa; (K.L.L.); (O.M.D.); (E.J.P.)
| | - Robert C. Luckay
- Department of Chemistry and Polymer Science, Stellenbosch University, Matieland, Stellenbosch 7602, South Africa;
| | - Ahmed A. Hussein
- Chemistry Department, Cape Peninsula University of Technology, Bellville 7535, South Africa;
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27
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Wu X, Zheng Q, Shen F, Song J, Luo Y, Fei X, Jiang W, Xie S, Ma X, Kuai L, Wang R, Ding X, Li M, Luo Y, Li B. The therapeutic efficacy and mechanism action of Si Cao formula in the treatment of psoriasis: A pilot clinical investigation and animal validation. JOURNAL OF ETHNOPHARMACOLOGY 2024; 323:117662. [PMID: 38160866 DOI: 10.1016/j.jep.2023.117662] [Citation(s) in RCA: 3] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/26/2023] [Revised: 12/17/2023] [Accepted: 12/24/2023] [Indexed: 01/03/2024]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Psoriasis is a chronic inflammation and relapsing disease that affected approximately 100 million individuals worldwide. In previous clinical study, it was observed that the topical application of Si Cao Formula (SCF) ameliorated psoriasis skin lesions and reduced the recurrence rate of patients over a period of three months. However, the precise mechanism remains unclear. AIM OF THE STUDY The objective of this study was to assess the effectiveness and safety of SCF in patients diagnosed with psoriasis and explore the molecular mechanisms that contribute to SCF's therapeutic efficacy in psoriasis treatment. MATERIALS AND METHODS A randomized, controlled, and pilot clinical study was performed. This study assessed 30 individuals diagnosed with mild to moderate plaque psoriasis. 15 of them underwent local SCF treatment, the others received calcipotriol intervention. The outcome measure focused on Psoriasis Area and Severity Index (PASI), Dermatology Life Quality Index (DLQI), and recurrence rate. In addition, IMQ-induced psoriasis-like mice model were used to assess the impact of SCF on ameliorating epidermal hyperplasia, suppressing angiogenesis, and modulating immune response. Furthermore, we performed bioinformatics analysis on transcriptome data obtained from skin lesions of mice model. This analysis allowed us to identify the targets and signaling pathways associated with the action of SCF. Subsequently, we conducted experimental validation to confirm the core targets. RESULTS Our clinical pilot study demonstrated that SCF could ameliorate skin lesions in psoriasis patients with comparable efficacy of calcipotriol in drop of PASI and DLQI scores. SCF exhibited a significantly reduced recurrence rate within 12 weeks (33.3%). Liquid Chromatography Mass Spectrometry (LC-MS) identified 41 active constituents of SCF (26 cations and 15 anions). Animal experiments showed SCF ameliorates the skin lesions of IMQ-induced psoriasis like mice model and suppresses epidermal hyperkeratosis and angiogenesis. There were 845 up-regulated and 764 down-regulated DEGs between IMQ and IMQ + SCF groups. GO analysis revealed that DEGs were linked to keratinization, keratinocyte differentiation, organic acid transport epidermal cell differentiation, and carboxylic acid transport interferon-gamma production. KEGG pathway analysis showed that SCF may play a vital part through IL-17 and JAK/STAT signaling pathway. In addition, SCF could reduce the number of positive cells expressing PCNA, CD31, pSTAT3, CD3, and F4/80 within the epidermis of psoriatic lesions, as well as the expression of Il-17a and Stat3 in IMQ-induced psoriasis mice. CONCLUSIONS Our research suggests that SCF serves as a reliable and efficient local approach for preventing and treating psoriasis. The discovery of plausible molecular mechanisms and therapeutic targets associated with SCF may support its broad implementation in clinical settings.
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Affiliation(s)
- Xinxin Wu
- Shanghai Skin Disease Hospital, School of Medicine, Tongji University, Shanghai, 200443, China
| | - Qi Zheng
- Shanghai Skin Disease Hospital, School of Medicine, Tongji University, Shanghai, 200443, China
| | - Fang Shen
- Shanghai Skin Disease Hospital, School of Medicine, Tongji University, Shanghai, 200443, China
| | - Jiankun Song
- Shanghai Skin Disease Hospital, School of Medicine, Tongji University, Shanghai, 200443, China
| | - Yue Luo
- Shanghai Skin Disease Hospital, School of Medicine, Tongji University, Shanghai, 200443, China
| | - Xiaoya Fei
- Shanghai Skin Disease Hospital, School of Medicine, Tongji University, Shanghai, 200443, China
| | - Wencheng Jiang
- Shanghai Skin Disease Hospital, School of Medicine, Tongji University, Shanghai, 200443, China
| | - Shaoqiong Xie
- Shanghai Skin Disease Hospital, School of Medicine, Tongji University, Shanghai, 200443, China
| | - Xin Ma
- Shanghai Skin Disease Hospital, School of Medicine, Tongji University, Shanghai, 200443, China; Department of Dermatology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 200437, China
| | - Le Kuai
- Department of Dermatology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 200437, China; Institute of Dermatology, Shanghai Academy of Traditional Chinese Medicine, Shanghai, 201203, China
| | - Ruiping Wang
- Shanghai Skin Disease Hospital, School of Medicine, Tongji University, Shanghai, 200443, China
| | - Xiaojie Ding
- Department of Dermatology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 200437, China; Institute of Dermatology, Shanghai Academy of Traditional Chinese Medicine, Shanghai, 201203, China
| | - Miao Li
- Department of Dermatology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 200437, China; Institute of Dermatology, Shanghai Academy of Traditional Chinese Medicine, Shanghai, 201203, China
| | - Ying Luo
- Department of Dermatology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 200437, China; Institute of Dermatology, Shanghai Academy of Traditional Chinese Medicine, Shanghai, 201203, China.
| | - Bin Li
- Shanghai Skin Disease Hospital, School of Medicine, Tongji University, Shanghai, 200443, China; Institute of Dermatology, Shanghai Academy of Traditional Chinese Medicine, Shanghai, 201203, China.
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28
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Abhithaj J, Sharanya CS, Arun KG, Jayadevi Variyar E, Sadasivan C. Trypsin is inhibited by phytocompounds liquiritin and terpinen-4-ol from the herb Glycyrrhiza glabra: in vitro and in silico studies. J Biomol Struct Dyn 2024; 42:2957-2964. [PMID: 37184119 DOI: 10.1080/07391102.2023.2212784] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2022] [Accepted: 04/27/2023] [Indexed: 05/16/2023]
Abstract
Serine proteases are a class of hydrolytic enzymes involved in various physiological functions like digestion, coagulation, fibrinolysis and immunity. The present study evaluates the serine protease inhibitory potential of phytochemicals liquiritin and terpinen-4-ol present in the herb Glycyrrhiza glabra L. using trypsin as the model enzyme. In silico studies showed that both the compounds have a significant binding affinity towards trypsin with a binding energy of -26.66 kcal/mol and -19.79 kcal/mol for liquiritin and terpinen-4-ol, respectively. Their binding affinity was confirmed through in vitro enzyme inhibition assays. The mode of inhibition was found to be uncompetitive. In order to explain the mode of inhibition, docking of the ligands to the enzyme-substrate complex was also done and binding energy was calculated after MD simulation. The energy values showed that the binding affinities of these compounds towards the enzyme substrate complex are more than that towards the enzyme alone. This explains the uncompetitive mode of inhibition.Communicated by Ramaswamy H. Sarma.
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Affiliation(s)
- J Abhithaj
- Department of Biotechnology & Microbiology and Inter University Centre for Bioscience, Kannur University, Kannur, Kerala, India
| | - C S Sharanya
- Department of Biosciences, Rajagiri College of Social Sciences (Autonomous), Cochin, Kerala, India
| | - K G Arun
- Department of Biotechnology & Microbiology and Inter University Centre for Bioscience, Kannur University, Kannur, Kerala, India
| | - E Jayadevi Variyar
- Department of Biotechnology & Microbiology and Inter University Centre for Bioscience, Kannur University, Kannur, Kerala, India
| | - C Sadasivan
- Department of Biotechnology & Microbiology and Inter University Centre for Bioscience, Kannur University, Kannur, Kerala, India
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29
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Huang Y, Li S, Pan J, Song C, Chen W, Zhang Y. Liquiritin Carbomer Gel Cold Paste Promotes Healing of Solar Dermatitis in Mice. Int J Mol Sci 2024; 25:3767. [PMID: 38612578 PMCID: PMC11011678 DOI: 10.3390/ijms25073767] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2024] [Revised: 03/19/2024] [Accepted: 03/26/2024] [Indexed: 04/14/2024] Open
Abstract
Ultraviolet radiation (UVR) has various effects on human cells and tissues, which can lead to a variety of skin diseases and cause inconvenience to people's lives. Among them, solar dermatitis is one of the important risk factors for malignant melanoma, so prevention and treatment of solar dermatitis is very necessary. Additionally, liquiritin (LQ) has anti-inflammatory effects. In this study, we aimed to evaluate the anti-inflammatory and pro-wound healing effects of liquiritin carbomer gel cold paste (LQ-CG-CP) in vitro and in vivo. The results of MTT experiments showed no cytotoxicity of LQ at concentrations of 40 μg/mL and below and cell damage at UVB irradiation doses above 60 mJ/cm2. Moreover, LQ can promote cell migration. ELISA results also showed that LQ inhibited the elevation of the inflammatory factors tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6) after UVB irradiation. In the mouse model of solar dermatitis, 2% LQ-CG-CP showed the best therapeutic efficacy for wound healing and relief of itching compared to MEIBAO moist burn moisturizer (MEBO). What is more, the results of skin histopathological examination show that LQ-CG-CP promotes re-epithelialization, shrinks wounds, and promotes collagen production, thus promoting wound healing. Simultaneously, LQ-CG-CP reduced TNF-α, IL-1β, and IL-6 expression. In addition, LQ-CG-CP was not observed to cause histopathological changes and blood biochemical abnormalities in mice. Overall, LQ-CG-CP has great potential for the treatment of solar dermatitis.
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Affiliation(s)
- Yanfang Huang
- School of Nursing, Guangdong Pharmaceutical University, Guangzhou 510006, China
| | - Sijia Li
- School of Nursing, Guangdong Pharmaceutical University, Guangzhou 510006, China
| | - Jinghua Pan
- School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou 510006, China
| | - Congjing Song
- School of Nursing, Guangdong Pharmaceutical University, Guangzhou 510006, China
| | - Weiqiang Chen
- School of Basic Medical Sciences, Guangdong Pharmaceutical University, Guangzhou 510006, China
| | - Yun Zhang
- School of Nursing, Guangdong Pharmaceutical University, Guangzhou 510006, China
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30
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Shen F, Gao C, Wang M, Ding X, Zhao H, Zhou M, Mao J, Kuai L, Li B, Wang D, Zhang H, Ma X. Therapeutic effects of the Qingre-Qushi recipe on atopic dermatitis through the regulation of gut microbiota and skin inflammation. Heliyon 2024; 10:e26063. [PMID: 38380039 PMCID: PMC10877368 DOI: 10.1016/j.heliyon.2024.e26063] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2023] [Revised: 02/06/2024] [Accepted: 02/07/2024] [Indexed: 02/22/2024] Open
Abstract
Accumulating evidence has highlighted a strong association between gut microbiota and the occurrence, development, prevention, and treatment of atopic dermatitis (AD). The regulation of gut microbial dysbiosis by oral traditional Chinese medicine (TCM) has garnered significant attention. In the treatment of AD, the TCM formula Qingre-Qushi Recipe (QRQS) has demonstrated clinical efficacy. However, both the therapeutic mechanisms of QRQS and its impact on gut microbiota remain unclear. Thus, our study aimed to assess the efficacy of QRQS and evaluate its influence on the composition and diversity of gut microbiota in AD animal models. First, we investigated the therapeutic effect of QRQS on AD using two animal models: filaggrin-deficient mice (Flaky tail, ft/ft) and MC903-induced AD-like mice. Subsequently, we explored its influence on the composition and diversity of gut microbiota. Our results demonstrated that QRQS treatment ameliorated the symptoms in both ft/ft mice and MC903-induced AD-like mice. It also reduced the levels of serum IgE and pro-inflammatory cytokines, including IL-1β, IL-4, IL-5, IL-9, IL-13, IL-17A, and TNF-α. Furthermore, QRQS remarkably regulated gut microbiota diversity by increasing Lactobacillaceae and decreasing Bacteroidales. The inflammatory factors in peripheral serum of ft/ft mice showed a close correlation with gut microbiota, as determined using the Spearman correlation coefficient. Additionally, PICRUSt analysis revealed an enrichment in ascorbate and aldarate metabolism, fatty acid metabolism and biosynthesis, and propanoate metabolism in the QRQS group compared to the ft/ft group. Finally, we identified liquiritin as the primary active ingredient of QRQS using ultra-high-performance liquid chromatography-high-resolution mass spectrometry (UPLC-HRMS). Our findings revealed that QRQS improved AD-like symptoms and alleviated skin inflammation in ft/ft and MC903-induced mice. This suggests that modulating the gut microbiota may help elucidate its anti-inflammation activation mechanism, highlighting a new therapeutic strategy that targets the intestinal flora to prevent and treat AD.
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Affiliation(s)
- Fang Shen
- Shanghai Skin Disease Hospital, School of Medicine, Tongji University, Shanghai, 200443, China
| | - Chunjie Gao
- Shanghai Skin Disease Hospital, School of Medicine, Tongji University, Shanghai, 200443, China
| | - Mingxia Wang
- Shanghai Skin Disease Hospital, School of Medicine, Tongji University, Shanghai, 200443, China
| | - Xiaojie Ding
- Institute of Dermatology, Shanghai Academy of Traditional Chinese Medicine, Shanghai, 201203, China
- Department of Dermatology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, 200437, China
| | - Hang Zhao
- Institute of Dermatology, Shanghai Academy of Traditional Chinese Medicine, Shanghai, 201203, China
- Department of Dermatology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, 200437, China
| | - Mi Zhou
- Institute of Dermatology, Shanghai Academy of Traditional Chinese Medicine, Shanghai, 201203, China
- Department of Dermatology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, 200437, China
| | - Jingyi Mao
- Department of Dermatology, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China
| | - Le Kuai
- Institute of Dermatology, Shanghai Academy of Traditional Chinese Medicine, Shanghai, 201203, China
- Department of Dermatology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, 200437, China
| | - Bin Li
- Shanghai Skin Disease Hospital, School of Medicine, Tongji University, Shanghai, 200443, China
- Institute of Dermatology, Shanghai Academy of Traditional Chinese Medicine, Shanghai, 201203, China
- Institute of Dermatology, School of Medicine, Tongji University, Shanghai, 200443, China
| | - Dongming Wang
- Department of Dermatology, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China
| | - Huimin Zhang
- Department of Dermatology, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China
| | - Xin Ma
- Shanghai Skin Disease Hospital, School of Medicine, Tongji University, Shanghai, 200443, China
- Department of Dermatology, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China
- Department of Dermatology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, 200437, China
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31
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Guo D, Wang Q, Li A, Li S, Wang B, Li Y, Yuan J, Guo T, Feng S. Liquiritin targeting Th17 cells differentiation and abnormal proliferation of keratinocytes alleviates psoriasis via NF-κB and AP-1 pathway. Phytother Res 2024; 38:174-186. [PMID: 37849425 DOI: 10.1002/ptr.8038] [Citation(s) in RCA: 4] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/16/2023] [Revised: 09/28/2023] [Accepted: 09/29/2023] [Indexed: 10/19/2023]
Abstract
Psoriasis is a common immune-mediated inflammatory skin disease, caused by disturbed interactions between keratinocytes and immune cells. Chinese medicine shows potential clinical application for its treatment. Liquiritin is a flavone compound extracted from licorice and shows potential antitussive, antioxidant and antiinflammatory effects, and therefore may have potential as a psoriasis therapeutic. The aim of this work was to examine the possible roles that liquiritin may have in treating psoriasis. HaCaT cells were stimulated by TNF-α with or without liquiritin, harvested for analysis by western blots and RT-qPCR, and the cellular supernatants were collected and analyzed by ELISA for cytokines. In addition, 4 groups of mice were examined: Normal, Vehicle, LQ-L and LQ-H. The mice were sacrificed after 6 days and analyzed using IHC, ELISA, RT-qPCR and flow cytometry. The results showed that liquiritin could significantly inhibit the progression of psoriasis both in vitro and in vivo. Liquiritin strongly suppressed the proliferation of HaCaT keratinocytes but did not affect cell viability. Moreover, liquiritin alleviated imiquimod-induced psoriasis-like skin inflammation and accumulation of Th17 cells and DCs in vivo. In TNF-α-induced HaCaT keratinocytes, both protein and mRNA expression levels of inflammatory cytokines were sharply decreased. In imiquimod-induced mice, the activation of NF-κB and AP-1 was reduced after treatment with liquiritin. Collectively, our results show that liquiritin might act as a pivotal regulator of psoriasis via modulating NF-κB and AP-1 signal pathways.
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Affiliation(s)
- Dandan Guo
- Medical College, Henan University of Chinese Medicine, Zhengzhou, China
| | - Qianqian Wang
- Medical College, Henan University of Chinese Medicine, Zhengzhou, China
| | - Aifang Li
- Medical College, Henan University of Chinese Medicine, Zhengzhou, China
| | - Shuxuan Li
- Medical College, Henan University of Chinese Medicine, Zhengzhou, China
| | - Baiyan Wang
- Medical College, Henan University of Chinese Medicine, Zhengzhou, China
| | - Yalan Li
- Medical College, Henan University of Chinese Medicine, Zhengzhou, China
| | - Juan Yuan
- School of Pharmacy, Henan University of Chinese Medicine, Zhengzhou, China
| | - Tao Guo
- School of Pharmacy, Henan University of Chinese Medicine, Zhengzhou, China
| | - Shuying Feng
- Medical College, Henan University of Chinese Medicine, Zhengzhou, China
- Henan Engineering Research Center for Chinese Medicine Foods for Special Medical Purpose, Zhengzhou, China
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32
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Sarra H, Salim B, Hocine A. Modeling the Antiviral Activity of Ginkgo biloba Polyphenols against Variola: In Silico Exploration of Inhibitory Candidates for VarTMPK and HssTMPK Enzymes. Curr Drug Discov Technol 2024; 21:e101023221938. [PMID: 37861017 DOI: 10.2174/0115701638261541230922095853] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/19/2023] [Revised: 08/11/2023] [Accepted: 08/18/2023] [Indexed: 10/21/2023]
Abstract
BACKGROUND The aim of this study is to use modeling methods to estimate the antiviral activity of natural molecules extracted from Ginkgo biloba for the treatment of variola which is a zoonotic disease posing a growing threat to human survival. The recent spread of variola in nonendemic countries and the possibility of its use as a bioterrorism weapon have made it a global threat once again. Therefore, the search for new antiviral therapies with reduced side effects is necessary. METHODS In this study, we examined the interactions between polyphenolic compounds from Ginkgo biloba, a plant known for its antiviral activity, and two enzymes involved in variola treatment, VarTMPK and HssTMPK, using molecular docking. RESULTS The obtained docking scores showed that among the 152 selected polyphenolic compounds; many ligands had high inhibitory potential according to the energy affinity. By considering Lipinski's rules, we found that Liquiritin and Olivil molecules are the best candidates to be developed into drugs that inhibit VarTMPK because of their high obtained scores compared to reference ligands, and zero violations of Lipinski's rules. We also found that ginkgolic acids have good affinities with HssTMPK and acceptable physicochemical properties to be developed into drugs administered orally. CONCLUSION Based on the obtained scores and Lipinski's rules, Liquiritin, Olivil, and ginkgolic acids molecules showed interesting results for both studied enzymes, indicating the existence of promising and moderate activity of these polyphenols for the treatment of variola and for possible multi-targeting. Liquiritin has been shown to exhibit anti-inflammatory effects on various inflammation- related diseases such as skin injury, hepatic inflammatory injury, and rheumatoid arthritis. Olivil has been shown to have antioxidant activity. Olivil derivatives have also been studied for their potential use as anticancer agents. Ginkgolic acids have been shown to have antimicrobial and antifungal properties. However, ginkgolic acids are also known to cause allergic reactions in some people. Therefore, future studies should consider these results and explore the potential of these compounds as antiviral agents. Further experimental studies in-vitro and in-vivo are required to validate and scale up these findings.
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Affiliation(s)
- Hamdani Sarra
- Department of Chemistry, Faculty of Sciences, Abou Bekr Belkaïd University, Tlemcen 13000, P.O. Box 119, Algeria
- Laboratory of Natural and Bioactive Substances (LASNABIO), Department of Chemistry, Faculty of Sciences, Abou Bekr Belkaïd University, Tlemcen 13000, P.O. Box 119, Algeria
| | - Bouchentouf Salim
- Laboratory of Natural and Bioactive Substances (LASNABIO), Department of Chemistry, Faculty of Sciences, Abou Bekr Belkaïd University, Tlemcen 13000, P.O. Box 119, Algeria
- Department of Process Engineering, Faculty of Technology, Doctor Tahar Moulay University of Saida, Algeria, Saïda 20000, BP 138 cité EN-NASR, Algeria
| | - Allali Hocine
- Department of Chemistry, Faculty of Sciences, Abou Bekr Belkaïd University, Tlemcen 13000, P.O. Box 119, Algeria
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González-May CA, Barradas-Castillo MDR, Perera-Rios JH, Gallegos-Tintoré S, Pérez-Izquierdo O, Aranda-González II. Dietary flavonoids may have a protective and therapeutic effect in Parkinson disease: A systematic review. Nutr Res 2024; 121:39-50. [PMID: 38039600 DOI: 10.1016/j.nutres.2023.10.004] [Citation(s) in RCA: 5] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2023] [Revised: 10/26/2023] [Accepted: 10/27/2023] [Indexed: 12/03/2023]
Abstract
Parkinson disease (PD) is characterized by the loss of dopaminergic neurons because of oxidative stress and neuroinflammation. Polyphenols in vegetables, known for their high antioxidant capacity, may prevent the onset, or delay the progression of the disease; among these, flavonoids are the most abundant class of polyphenols in foods. Clinical and cohort studies have evaluated the effect of polyphenol consumption on the risk of developing PD or of attenuating the symptoms after diagnosis; therefore, it is necessary to integrate the scientific evidence into making dietary recommendations. The objective of this study was to perform a systematic review of randomized controlled trials and cohort studies that have investigated the use of polyphenols in PD. The studies were identified through the PubMed, Science Direct, Scielo, and Web of Science databases. A total of 1100 studies were found; these were analyzed and filtered by 2 independent reviewers. After completion, 5 studies were included (3 randomized controlled trials and 2 cohort studies). The consumption of flavonoids, anthocyanins, or 2-5 servings/week of specific foods (apples, red wine, blueberries, and strawberries) reduces the risk of PD and associated mortality. Treatment with licorice, curcumin, or cocoa, which are rich in flavonoids and other polyphenols, improves motor function in PD patients. No statistically significant differences were found in quality of life, disease progression or nonmotor symptoms such as cognitive ability and mood. Although cohort studies suggest a neuroprotective effect, further clinical studies are urgently needed to evaluate the effect of specific flavonoids and other polyphenols in PD.
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Affiliation(s)
| | | | | | - Santiago Gallegos-Tintoré
- Facultad de Ingeniería Química, Universidad Autónoma de Yucatán, Colonia Chuburná Hidalgo Inn, 97203, Mérida, Yucatán, México
| | - Odette Pérez-Izquierdo
- Facultad de Medicina, Universidad Autónoma de Yucatán, Centro, 97000, Mérida, Yucatán, México
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Wang M, Liu M, Tang L, Shen L, Xiao J, Li R. RETRACTED ARTICLE: Liquiritin reduces ferroptosis in doxorubicin-induced cardiotoxicity through targeting SLC7A11/GPX4 pathway. NAUNYN-SCHMIEDEBERG'S ARCHIVES OF PHARMACOLOGY 2024; 397:627. [PMID: 37160483 DOI: 10.1007/s00210-023-02515-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/06/2023] [Accepted: 04/25/2023] [Indexed: 05/11/2023]
Affiliation(s)
- Mei Wang
- The Second Affiliated Hospital, Department of Pharmacy, Hengyang Medical School, University of South China, Hengyang, 421001, Hunan, China
- Department of Pharmacy and Pharmacology, School of Pharmaceutical Science, Hengyang Medical School, University of South China, Hengyang, 421000, Hunan, China
| | - Meng Liu
- The Second Affiliated Hospital, Department of Pharmacy, Hengyang Medical School, University of South China, Hengyang, 421001, Hunan, China
- Department of Pharmacy and Pharmacology, School of Pharmaceutical Science, Hengyang Medical School, University of South China, Hengyang, 421000, Hunan, China
| | - Lijing Tang
- The Second Affiliated Hospital, Department of Pharmacy, Hengyang Medical School, University of South China, Hengyang, 421001, Hunan, China
| | - Lixian Shen
- The Second Affiliated Hospital, Department of Pharmacy, Hengyang Medical School, University of South China, Hengyang, 421001, Hunan, China
| | - Junhui Xiao
- The Second Affiliated Hospital, Department of Pharmacy, Hengyang Medical School, University of South China, Hengyang, 421001, Hunan, China.
| | - Rong Li
- The Second Affiliated Hospital, Department of Pharmacy, Hengyang Medical School, University of South China, Hengyang, 421001, Hunan, China.
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Zhu K, Wang L, Liao T, Li W, Zhou J, You Y, Shi J. Progress in the development of TRPV1 small-molecule antagonists: Novel Strategies for pain management. Eur J Med Chem 2023; 261:115806. [PMID: 37713804 DOI: 10.1016/j.ejmech.2023.115806] [Citation(s) in RCA: 12] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2023] [Revised: 09/06/2023] [Accepted: 09/07/2023] [Indexed: 09/17/2023]
Abstract
Transient receptor potential vanilloid 1 (TRPV1) channels are widely distributed in sensory nerve endings, the central nervous system, and other tissues, functioning as ion channel proteins responsive to thermal pain and chemical stimuli. In recent years, the TRPV1 receptor has garnered significant interest as a potential therapeutic approach for various pain-related disorders, particularly TRPV1 antagonists. The present review offers a comprehensive, systematic exploration of both first- and second-generation TRPV1 antagonists in the context of pain management. Antagonists are categorized and explicated according to their structural characteristics. Detailed examination of binding modes, structural features, and pharmacological activities, alongside a critical appraisal of the advantages and limitations inherent to typical compounds within each structural category, are undertaken. Detailed discussions of the binding modes, structural features, pharmacological activities, advantages, and limitations of typical compounds within each structural category offer valuable insights and guidance for the future research and development of safer, more effective, and more targeted TRPV1 antagonists.
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Affiliation(s)
- Kun Zhu
- Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, 610072, China
| | - Lin Wang
- Department of Pharmacy, Personalized Drug Therapy Key Laboratory of Sichuan Province, Sichuan Academy of Medical Science & Sichuan Provincial People's Hospital, Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, 610072, China; State Key Laboratory of Biotherapy, Collaborative Innovation Center of Biotherapy and Cancer Center, West China Hospital of Sichuan University, Chengdu, 610041, China
| | - TingTing Liao
- Department of Endocrinology, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, 610072, China
| | - Wen Li
- Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, 610072, China
| | - Jing Zhou
- Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, 610072, China
| | - Yaodong You
- Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, 610072, China; TCM Regulating Metabolic Diseases Key Laboratory of Sichuan Province, Chengdu, 610072, China.
| | - Jianyou Shi
- Department of Pharmacy, Personalized Drug Therapy Key Laboratory of Sichuan Province, Sichuan Academy of Medical Science & Sichuan Provincial People's Hospital, Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, 610072, China; State Key Laboratory of Southwestern Chinese Medicine Resources, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, China.
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Hong G, Zhou L, Zheng G, Zheng X, Chen Z, He W, Wei Q. A novel Glycyrrhiza glabra extract liquiritin targeting NFATc1 activity and ROS levels to counteract ovariectomy-induced osteoporosis and bone loss in murine model. Front Pharmacol 2023; 14:1287827. [PMID: 38026985 PMCID: PMC10663366 DOI: 10.3389/fphar.2023.1287827] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2023] [Accepted: 10/03/2023] [Indexed: 12/01/2023] Open
Abstract
Osteoporosis, a prevalent osteolytic condition worldwide, necessitates effective strategies to inhibit excessive bone resorption by curbing osteoclast hyperactivation. Liquiritin (LIQ), an flavanone derivative employed in acute lung injury and rheumatoid arthritis treatment, possesses an unclear role in addressing excessive bone resorption. In this investigation, we found that LIQ demonstrates the ability to inhibit osteoclast formation and the bone-resorbing activity induced by RANKL. At a specific concentration, LIQ significantly attenuated NF-κB-Luc activity induced by RANKL and curtailed NF-κB activation in RANKL-stimulated RAW264.7 cells, resulting in reduced IκB-α breakdown and diminished nuclear NF-κB levels. Furthermore, LIQ markedly inhibited RANKL-induced NFATc1 activation, as evidenced by diminished NFATc1 luciferase activity, reduced NFATc1 mRNA levels, and decreased nuclear NFATc1 protein levels. Subsequent experiments demonstrated that LIQ effectively restrained the RANKL-induced elevation of intracellular calcium as well as reactive oxygen species. Additionally, LIQ exhibited a downregulating effect on the expression of osteoclast-specific genes, which include Acp5, Cathepsin K, Atp6v0d2, Nfatc1, c-Fos, and Mmp9. Notably, our findings revealed the potential of LIQ to counteract decreased bone density in mice that underwent ovariectomy. Collectively, the data indicate that LIQ impedes osteoclast formation triggered by RANKL and the subsequent reduction in bone mass by mitigating ROS levels and suppressing the Ca2+/MAPK-NFATc1 signaling pathway, suggesting its promising candidacy as a therapeutic agent for RANKL-mediated osteoporosis.
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Affiliation(s)
- Guoju Hong
- Traumatology and Orthopedics Institute, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, China
- Department of Orthopaedics, The Third Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, China
| | - Lin Zhou
- Key Laboratory of Biological Targeting Diagnosis, Department of Endocrinology, Therapy and Rehabilitation of Guangdong Higher Education Institutes, The Fifth Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, China
| | - Guanqiang Zheng
- Department of Rehabilitation, The Third Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, China
| | - Xiaoxia Zheng
- The Third Clinical Medical College, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, China
| | - Zhenqiu Chen
- Department of Orthopaedics, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, China
| | - Wei He
- Traumatology and Orthopedics Institute, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, China
- Department of Orthopaedics, The Third Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, China
| | - Qiushi Wei
- Traumatology and Orthopedics Institute, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, China
- Department of Orthopaedics, The Third Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, China
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Yang R, Wei L, Wang J, Huang S, Mo P, Chen Q, Zheng P, Chen J, Zhang S, Chen J. Chemical characterization and metabolic profiling of Xiao-Er-An-Shen Decoction by UPLC-QTOF/MS. Front Pharmacol 2023; 14:1219866. [PMID: 38027020 PMCID: PMC10652787 DOI: 10.3389/fphar.2023.1219866] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2023] [Accepted: 10/17/2023] [Indexed: 12/01/2023] Open
Abstract
Background: Xiao-Er-An-Shen decoction (XEASD), a TCM formula composed of sixteen Chinese medicinal herbs, has been used to alleviate tic disorders (TD) in clinical practice for many years. However, the chemical basis underlying the therapeutic effects of XEASD in the treatment of TD remains unknown. Purpose: The present study aimed to determine the major chemical components of XEASD and its prototype compounds and metabolites in mice biological samples. Methods: The chemical constituents in XEASD were identified using ultra-high Performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry (UPLC-Q-TOF-MS/MS). Following this, XEASD was orally administered to mice, and samples of plasma, urine, feces, bile, and tissue were collected in order to identify effective compounds for the prevention or treatment of TD. Result: Of the total 184 compounds identified to be discriminated in the XEASD, comprising 44 flavonoids, 26 phenylpropanoids, 16 coumarins, 16 triterpenoids, 14 amino acids, 13 organic acids, 13 alkaloids, 13 ketones, 10 cyclic enol ether terpenes, 7 citrullines, 3 steroids, and 5 anthraquinones, and others. Furthermore, we summarized 54 prototype components and 78 metabolic products of XEASD, measured with biological samples, by estimating metabolic principal components, with four prototype compounds detected in plasma, 58 prototypes discriminated in urine, and 40 prototypes identified in feces. These results indicate that the Oroxylin A glucuronide from Citri reticulatae pericarpium (CRP) is a major compound with potential therapeutic effects identified in brain, while operating positive effect in inhibiting oxidative stress in vitro. Conclusion: In summary, our work delineates the chemical basis underlying the complexity of XEASD, providing insights into the therapeutic and metabolic pathways for TD. Various types of chemicals were explored in XEASD, including flavonoids, phenylpropanoids, coumarins, organic acids, triterpenoid saponins, and so on. This study can promote the further pharmacokinetic and pharmacological evaluation of XEASD.
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Affiliation(s)
- Ruipei Yang
- Shenzhen Key Laboratory of Hospital Chinese Medicine Preparation, Shenzhen Traditional Chinese Medicine Hospital, The Fourth Clinical Medical College of Guangzhou University of Chinese Medicine, Shenzhen, Guangdong, China
- School of Medicine, Life and Health Sciences, The Chinese University of Hong Kong, Shenzhen, China
- KMHD GeneTech Co., Ltd., Shenzhen, Guangdong, China
| | - Lifang Wei
- Shenzhen Key Laboratory of Hospital Chinese Medicine Preparation, Shenzhen Traditional Chinese Medicine Hospital, The Fourth Clinical Medical College of Guangzhou University of Chinese Medicine, Shenzhen, Guangdong, China
| | - Jie Wang
- Shenzhen People’s Hospital, Shenzhen, Guangdong, China
| | - Shiying Huang
- Shenzhen Key Laboratory of Hospital Chinese Medicine Preparation, Shenzhen Traditional Chinese Medicine Hospital, The Fourth Clinical Medical College of Guangzhou University of Chinese Medicine, Shenzhen, Guangdong, China
| | - Pingli Mo
- Shenzhen Key Laboratory of Hospital Chinese Medicine Preparation, Shenzhen Traditional Chinese Medicine Hospital, The Fourth Clinical Medical College of Guangzhou University of Chinese Medicine, Shenzhen, Guangdong, China
| | - Qiugu Chen
- Shenzhen Key Laboratory of Hospital Chinese Medicine Preparation, Shenzhen Traditional Chinese Medicine Hospital, The Fourth Clinical Medical College of Guangzhou University of Chinese Medicine, Shenzhen, Guangdong, China
| | - Ping Zheng
- Shenzhen Key Laboratory of Hospital Chinese Medicine Preparation, Shenzhen Traditional Chinese Medicine Hospital, The Fourth Clinical Medical College of Guangzhou University of Chinese Medicine, Shenzhen, Guangdong, China
| | - Jihang Chen
- School of Medicine, Life and Health Sciences, The Chinese University of Hong Kong, Shenzhen, China
| | - Shangbin Zhang
- Shenzhen Key Laboratory of Hospital Chinese Medicine Preparation, Shenzhen Traditional Chinese Medicine Hospital, The Fourth Clinical Medical College of Guangzhou University of Chinese Medicine, Shenzhen, Guangdong, China
| | - Jianping Chen
- Shenzhen Key Laboratory of Hospital Chinese Medicine Preparation, Shenzhen Traditional Chinese Medicine Hospital, The Fourth Clinical Medical College of Guangzhou University of Chinese Medicine, Shenzhen, Guangdong, China
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Lee B, Kwon CY, Suh HW, Kim YJ, Kim KI, Lee BJ, Lee JH. Herbal medicine for the treatment of chronic cough: a systematic review and meta-analysis. Front Pharmacol 2023; 14:1230604. [PMID: 37920213 PMCID: PMC10619915 DOI: 10.3389/fphar.2023.1230604] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2023] [Accepted: 09/28/2023] [Indexed: 11/04/2023] Open
Abstract
Objectives: Chronic cough is a frequent condition worldwide that significantly impairs quality of life. Herbal medicine (HM) has been used to treat chronic cough due to the limited effectiveness of conventional medications. This study aimed to summarize and determine the effects of HM on patients with chronic cough. Methods: A comprehensive search of 11 databases was conducted to find randomized controlled clinical trials (RCTs) that reported the effects of HM for patients with chronic cough on 16 March 2023. The primary outcome was cough severity, and the secondary outcomes included cough-related quality of life, cough frequency, total effective rate (TER), and cough recurrence rate. The methodological quality of the included studies was assessed using the Cochrane risk of bias tool, and the certainty of the evidence for effect estimates was assessed using the Grading of Recommendations, Assessment, Development, and Evaluations tool. Results: A total of 80 RCTs comprising 7,573 patients were included. When HM was used as an alternative therapy to conventional medication, there were inconsistent results in improving cough severity. However, HM significantly improved cough-related quality of life and TER and significantly lowered the cough recurrence rate compared with conventional medication. When used as an add-on therapy to conventional medication, HM significantly improved cough severity, cough-related quality of life, and TER and significantly lowered the recurrence rate. In addition, HM had a significantly lower incidence of adverse events when used as an add-on or alternative therapy to conventional medication. The subgroup analysis according to age and cause of cough also showed a statistically consistent correlation with the overall results. The certainty of the evidence for the effect of HM was generally moderate to low due to the risk of bias in the included studies. Conclusion: HM may improve cough severity and cough-related quality of life, and lower the cough recurrence rate and incidence of adverse events in patients with chronic cough. However, due to the high risk of bias and clinical heterogeneity of the included studies, further high-quality placebo-controlled clinical trials should be conducted using a validated and objective assessment tool. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023418736, CRD42023418736.
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Affiliation(s)
- Boram Lee
- KM Science Research Division, Korea Institute of Oriental Medicine, Daejeon, Republic of Korea
| | - Chan-Young Kwon
- Department of Oriental Neuropsychiatry, Dong-eui University College of Korean Medicine, Busan, Republic of Korea
| | - Hyo-Weon Suh
- Health Policy Research Team, Division of Healthcare Research, National Evidence-based Healthcare Collaborating Agency, Seoul, Republic of Korea
| | - Ye Ji Kim
- Department of Korean Pediatrics, Kyung Hee University Medical Center, Seoul, Republic of Korea
| | - Kwan-Il Kim
- Division of Allergy, Immune and Respiratory System, Department of Internal Medicine, College of Korean Medicine, Kyung Hee Medical Center, Kyung Hee University, Seoul, Republic of Korea
| | - Beom-Joon Lee
- Division of Allergy, Immune and Respiratory System, Department of Internal Medicine, College of Korean Medicine, Kyung Hee Medical Center, Kyung Hee University, Seoul, Republic of Korea
| | - Jun-Hwan Lee
- KM Science Research Division, Korea Institute of Oriental Medicine, Daejeon, Republic of Korea
- Korean Medicine Life Science, University of Science and Technology (UST), Campus of Korea Institute of Oriental Medicine, Daejeon, Republic of Korea
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Cheng Y, Liu Z, Xu B, Song P, Chao Z. Comprehensive metabolomic variations of hawthorn before and after insect infestation based on the combination analysis of 1H NMR and UPLC-MS. Curr Res Food Sci 2023; 7:100616. [PMID: 37881336 PMCID: PMC10594559 DOI: 10.1016/j.crfs.2023.100616] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2023] [Revised: 09/25/2023] [Accepted: 10/08/2023] [Indexed: 10/27/2023] Open
Abstract
Hawthorn, the sliced and dried ripe fruits of Crataegus pinnatifida Bge. Var. Major N. E. Br. (Rosaceae), is an edible and medicinal substance with a variety of health-promoting benefits. Hawthorn needs to be stored in warehouses after harvesting to meet people's perennial demand. However, it is easily infested by insects of Plodia interpunctella and Tribolium castaneum during storage, which inevitably leads to poor quality and causes adverse effects on people's health. So far, there has been no report on insect-infested hawthorn. In this study, we analyzed the changes of metabolites in hawthorn before and after insect infestation and screened out potential biomarkers to effectively and quickly detect the occurrence of insect infestation. A combination analysis of 1H nuclear magnetic resonance (NMR) and ultra-performance liquid chromatography-mass spectrometry (UPLC-MS) was used to identify the primary and secondary metabolites. By the comparison of hawthorn and insect-infested hawthorn samples, it was found that the differences were mainly manifested in the content of metabolites. The metabolites of 32 and 1463 were identified by 1H NMR and UPLC-MS analysis, respectively. According to the parameters of VIP >1 and P < 0.05, 10 differential metabolites were screened from 1H NMR analysis. Based on the parameters of VIP >1.0, P < 0.05, and (FC) > 1 or < 1, 47 differential metabolites were screened from UPLC-MS analysis. Therefore, a total of 57 differential metabolites were considered as differential biomarkers. The heat map analysis showed that the content of some differential biomarkers with significant pharmacological activities decreased after insect infestation. Through receiver operating characteristic (ROC) curve assessment, 52 differential biomarkers (6 of 1H NMR analysis and 46 of UPLC-MS analysis) were screened to distinguish whether insect infestation occurred in hawthorn. This is the first report on the changes of metabolites between hawthorn and insect-infested hawthorn and on the screening of differential biomarkers for monitoring insects. These results contributed to evaluate quality of hawthorn and ensure food safety for consumers. It also laid a foundation for further research on the infestation mechanism and safe storage monitoring in hawthorn.
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Affiliation(s)
- Yunxia Cheng
- Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, 100700, China
| | - Zhenying Liu
- Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, 100700, China
| | - Bo Xu
- Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, 100700, China
| | - Pingping Song
- Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, 100700, China
| | - Zhimao Chao
- Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, 100700, China
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Akash S, Bayıl I, Mahmood S, Mukerjee N, Mili TA, Dhama K, Rahman MA, Maitra S, Mohany M, Al-Rejaie SS, Ali N, Semwal P, Sharma R. Mechanistic inhibition of gastric cancer-associated bacteria Helicobacter pylori by selected phytocompounds: A new cutting-edge computational approach. Heliyon 2023; 9:e20670. [PMID: 37876433 PMCID: PMC10590806 DOI: 10.1016/j.heliyon.2023.e20670] [Citation(s) in RCA: 12] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/03/2023] [Revised: 09/09/2023] [Accepted: 10/04/2023] [Indexed: 10/26/2023] Open
Abstract
Background Helicobacter pylori (H. pylori) is a persistent bacterial inhabitant in the stomachs of approximately half the global populace. This bacterium is directly linked to chronic gastritis, leading to a heightened risk of duodenal and gastric ulcer diseases, and is the predominant risk factor for gastric cancer - the second most common cause of cancer-related deaths globally. The increasing prevalence of antibiotic resistance necessitates the exploration of innovative treatment alternatives to mitigate the H. pylori menace. Methods Initiating our study, we curated a list of thirty phytochemicals based on previous literature and subjected them to molecular docking studies. Subsequently, eight phytocompounds-Glabridin, Isoliquiritin, Sanguinarine, Liquiritin, Glycyrrhetic acid, Beta-carotin, Diosgenin, and Sarsasapogenin-were meticulously chosen based on superior binding scores. These were further subjected to an extensive computational analysis encompassing ADMET profiling, drug-likeness evaluation, principal component analysis (PCA), and molecular dynamic simulations (MDs) in comparison with the conventional drug, Mitomycin. Results The natural compounds investigated demonstrated superior docking affinities to H. pylori targets compared to the standard Mitomycin. Notably, the phytocompounds Diosgenin and Sarsasapogenin stood out due to their exceptional binding affinities and pharmacokinetic properties, including favorable ADMET profiles. Conclusion Our comprehensive and technologically-advanced approach showcases the potential of identified phytocompounds as pioneering therapeutic agents against H. pylori-induced gastric malignancies. In light of our promising in silico results, we recommend these natural compounds as potential candidates for advancing H. pylori-targeted drug development. Given their potential, we strongly advocate for subsequent in vitro and in vivo studies to validate their therapeutic efficacy against this formidable gastrointestinal bacterium.
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Affiliation(s)
- Shopnil Akash
- Department of Pharmacy, Faculty of Allied Health Sciences, Daffodil International University, Birulia, 1216, Ashulia, Dhaka, Bangladesh
| | - Imren Bayıl
- Department of Bioinformatics and Computational Biology, Gaziantep University, Turkey
| | - Sajjat Mahmood
- Department of Microbiology, Jagannath University, Chittaranjan Avenue in Sadarghat, Dhaka, 1100, Bangladesh
| | - Nobendu Mukerjee
- Center for Global Health Research, Saveetha Medical College and Hospital, Saveetha Institute Of Medical and Technical Sciences, Chennai, India
- Department of Microbiology, West Bengal State University, West Bengal, Kolkata, 700126, India
- Department of Health Sciences, Novel Global Community Educational Foundation, Hebersham, NSW, Australia
| | - Tamanna Akter Mili
- Department of Pharmacy, University of Asia Pacific, 74/A Green Rd, Dhaka, 1205, Bangladesh
| | - Kuldeep Dhama
- Division of Pathology, ICAR-Indian Veterinary Research Institute (IVRI), Izatnagar, 243122, Bareilly, Uttar Pradesh, India
| | | | - Swastika Maitra
- Department of Microbiology, Adamas University, West Bengal, Kolkata, 700126, India
| | - Mohamed Mohany
- Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, P.O. Box 55760, Riyadh, 1145, Saudi Arabia
| | - Salim S. Al-Rejaie
- Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, P.O. Box 55760, Riyadh, 1145, Saudi Arabia
| | - Nemat Ali
- Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, P.O. Box 55760, Riyadh, 1145, Saudi Arabia
| | - Prabhakar Semwal
- Department of Biotechnology, Graphic Era University, Dehradun, Uttarakhand, 248002, India
| | - Rohit Sharma
- Department of Rasa Shastra and Bhaishajya Kalpana, Faculty of Ayurveda, Institute of Medical Science, Banaras Hindu University, Varanasi, 221005, India
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Chen X, Yang JB, Cao HH, Fang XC, Liu SH, Zou LF, Yu JH, Zuo JP, Zhao W, Lu ZB, Liu JS, Yu LZ. Liang-Ge-San inhibits dengue virus serotype 2 infection by reducing caveolin1-induced cytoplasmic heat shock protein 70 translocation into the plasma membrane. PHYTOMEDICINE : INTERNATIONAL JOURNAL OF PHYTOTHERAPY AND PHYTOPHARMACOLOGY 2023; 119:154977. [PMID: 37506573 DOI: 10.1016/j.phymed.2023.154977] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/03/2023] [Revised: 07/05/2023] [Accepted: 07/15/2023] [Indexed: 07/30/2023]
Abstract
BACKGROUND Dengue virus (DENV) is a major public health threat. However, there are no specific therapeutic drugs for DENV. Many Chinese heat-cleaning formulas, such as Liang-Ge-San (LGS), have been frequently used in the virus-induced diseases. The antiviral effect of LGS has not been reported yet. PURPOSE In this study, the effect of LGS on the inhibition of dengue virus serotype 2 (DENV-2) was investigated and the relevant mechanism was explored. METHODS High-performance liquid chromatography was applied to analyze the chemical characterization of LGS. The in vitro antiviral activities of LGS against DENV-2 were evaluated by time-of-drug-addition assay. The binding of heat shock protein 70 (Hsp70) and envelope (E) protein or caveolin1 (Cav1) were analyzed by immunofluorescence and immunoprecipitation assays. Then the role of Cav1 in the anti-DENV-2 effects of LGS was further examined. DENV-2 infected Institute of Cancer Research suckling mice (n = 10) and AG129 mice (n = 8) were used to examine the protective effects of LGS. RESULTS It was found that geniposide, liquiritin, forsythenside A, forsythin, baicalin, baicalein, rhein, and emodin maybe the characteristic components of LGS. LGS inhibited the early stage of DENV-2 infection, decreased the expression levels of viral E and non-structural protein 1 (NS1) proteins. LGS also reduced E protein and Hsp70 binding and attenuated the translocation of Hsp70 from cytoplasm to the cell membrane. Moreover, LGS decreased the binding of Hsp70 to Cav1. Further study showed that the overexpression of Cav1 reversed LGS-mediated E protein and Hsp70 inhibition in the plasma membrane. In the in vivo study, LGS was highly effective in prolonging the survival time, reducing viral loads. CONCLUSION This work demonstrates for the first time that LGS exerts anti-DENV-2 activity in vitro and in vivo. LGS decreases DENV-2-stimulated cytoplasmic Hsp70 translocation into the plasma membrane by Cav1 inhibition, thereby inhibiting the early stage of virus infection. These findings indicate that LGS may be a candidate for the treatment of DENV.
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Affiliation(s)
- Xi Chen
- Third Level Research Laboratory of State Administration of Traditional Chinese Medicine, School of Traditional Chinese Medicine, Southern Medical University, Guangzhou 510515, PR China; Guangdong Provincial Key Laboratory of Chinese Medicine Pharmaceutics, School of Traditional Chinese Medicine, Southern Medical University, Guangzhou 510515, PR China
| | - Jia-Bin Yang
- Third Level Research Laboratory of State Administration of Traditional Chinese Medicine, School of Traditional Chinese Medicine, Southern Medical University, Guangzhou 510515, PR China; Guangdong Provincial Key Laboratory of Chinese Medicine Pharmaceutics, School of Traditional Chinese Medicine, Southern Medical University, Guangzhou 510515, PR China
| | - Hui-Hui Cao
- Third Level Research Laboratory of State Administration of Traditional Chinese Medicine, School of Traditional Chinese Medicine, Southern Medical University, Guangzhou 510515, PR China; Guangdong Provincial Key Laboratory of Chinese Medicine Pharmaceutics, School of Traditional Chinese Medicine, Southern Medical University, Guangzhou 510515, PR China
| | - Xiao-Chuan Fang
- Third Level Research Laboratory of State Administration of Traditional Chinese Medicine, School of Traditional Chinese Medicine, Southern Medical University, Guangzhou 510515, PR China; Guangdong Provincial Key Laboratory of Chinese Medicine Pharmaceutics, School of Traditional Chinese Medicine, Southern Medical University, Guangzhou 510515, PR China
| | - Shan-Hong Liu
- Third Level Research Laboratory of State Administration of Traditional Chinese Medicine, School of Traditional Chinese Medicine, Southern Medical University, Guangzhou 510515, PR China; Guangdong Provincial Key Laboratory of Chinese Medicine Pharmaceutics, School of Traditional Chinese Medicine, Southern Medical University, Guangzhou 510515, PR China
| | - Li-Fang Zou
- Third Level Research Laboratory of State Administration of Traditional Chinese Medicine, School of Traditional Chinese Medicine, Southern Medical University, Guangzhou 510515, PR China; Guangdong Provincial Key Laboratory of Chinese Medicine Pharmaceutics, School of Traditional Chinese Medicine, Southern Medical University, Guangzhou 510515, PR China
| | - Jian-Hai Yu
- Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University, Guangzhou, 510515, PR China
| | - Jian-Ping Zuo
- Laboratory of Immunopharmacology, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, PR China
| | - Wei Zhao
- Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University, Guangzhou, 510515, PR China
| | - Zi-Bin Lu
- Third Level Research Laboratory of State Administration of Traditional Chinese Medicine, School of Traditional Chinese Medicine, Southern Medical University, Guangzhou 510515, PR China; Guangdong Provincial Key Laboratory of Chinese Medicine Pharmaceutics, School of Traditional Chinese Medicine, Southern Medical University, Guangzhou 510515, PR China.
| | - Jun-Shan Liu
- Third Level Research Laboratory of State Administration of Traditional Chinese Medicine, School of Traditional Chinese Medicine, Southern Medical University, Guangzhou 510515, PR China; Guangdong Provincial Key Laboratory of Chinese Medicine Pharmaceutics, School of Traditional Chinese Medicine, Southern Medical University, Guangzhou 510515, PR China; Department of Pharmacy, Zhujiang Hospital, Southern Medical University, Guangzhou, China, 510280, PR China.
| | - Lin-Zhong Yu
- Third Level Research Laboratory of State Administration of Traditional Chinese Medicine, School of Traditional Chinese Medicine, Southern Medical University, Guangzhou 510515, PR China; Guangdong Provincial Key Laboratory of Chinese Medicine Pharmaceutics, School of Traditional Chinese Medicine, Southern Medical University, Guangzhou 510515, PR China.
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Choi NR, Kwon MJ, Choi WG, Kim SC, Park JW, Nam JH, Kim BJ. The traditional herbal medicines mixture, Banhasasim-tang, relieves the symptoms of irritable bowel syndrome via modulation of TRPA1, NaV1.5 and NaV1.7 channels. JOURNAL OF ETHNOPHARMACOLOGY 2023; 312:116499. [PMID: 37059250 DOI: 10.1016/j.jep.2023.116499] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/05/2023] [Revised: 04/10/2023] [Accepted: 04/12/2023] [Indexed: 05/08/2023]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE The cause of irritable bowel syndrome (IBS), a functional gastrointestinal (GI) disorder, remains unclear. Banhasasim-tang (BHSST), a traditional herbal medicines mixture, mainly used to treat GI-related diseases, may have a potential in IBS treatment. IBS is characterized by abdominal pain as the main clinical symptom, which seriously affects the quality of life. AIM OF THE STUDY We conducted a study to evaluate the effectiveness of BHSST and its mechanisms of action in treating IBS. MATERIALS AND METHODS We evaluated the efficacy of BHSST in a zymosan-induced diarrhea-predominant animal model of IBS. Electrophysiological methods were used to confirm modulation of transient receptor potential (TRP) and voltage-gated Na+ (NaV) ion channels, which are associated mechanisms of action. RESULTS Oral administration of BHSST decreased colon length, increased stool scores, and increased colon weight. Weight loss was also minimized without affecting food intake. In mice administered with BHSST, the mucosal thickness was suppressed, making it similar to that of normal mice, and the degree of tumor necrosis factor-α was severely reduced. These effects were similar to those of the anti-inflammatory drug-sulfasalazine-and antidepressant-amitriptyline. Moreover, pain-related behaviors were substantially reduced. Additionally, BHSST inhibited TRPA1, NaV1.5, and NaV1.7 ion channels associated with IBS-mediated visceral hypersensitivity. CONCLUSIONS In summary, the findings suggest that BHSST has potential beneficial effects on IBS and diarrhea through the modulation of ion channels.
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Affiliation(s)
- Na Ri Choi
- Department of Longevity and Biofunctional Medicine, Pusan National University School of Korean Medicine, Yangsan, 50612, Republic of Korea.
| | - Min Ji Kwon
- Department of Longevity and Biofunctional Medicine, Pusan National University School of Korean Medicine, Yangsan, 50612, Republic of Korea.
| | - Woo-Gyun Choi
- Department of Longevity and Biofunctional Medicine, Pusan National University School of Korean Medicine, Yangsan, 50612, Republic of Korea.
| | - Sang Chan Kim
- College of Oriental Medicine Daegu Haany University, Gyeongsan, 38610, Republic of Korea
| | - Jae-Woo Park
- Department of Clinical Korean Medicine, Graduate School of Kyung Hee University, Seoul, 02447, Republic of Korea; Department of Gastroenterology, College of Korean Medicine, Kyung Hee University, Seoul, 02447, Republic of Korea.
| | - Joo Hyun Nam
- Department of Physiology, Dongguk University College of Medicine, Kyungju, 38066, Republic of Korea; Channelopathy Research Center (CRC), Dongguk University College of Medicine, Goyang, 10326, Republic of Korea.
| | - Byung Joo Kim
- Department of Longevity and Biofunctional Medicine, Pusan National University School of Korean Medicine, Yangsan, 50612, Republic of Korea.
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Liu H, Feng C, Yang T, Zhang Z, Wei X, Sun Y, Zhang L, Li W, Yu D. Combined metabolomics and gut microbiome to investigate the effects and mechanisms of Yuquan Pill on type 2 diabetes in rats. J Chromatogr B Analyt Technol Biomed Life Sci 2023; 1222:123713. [PMID: 37059008 DOI: 10.1016/j.jchromb.2023.123713] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/07/2022] [Revised: 03/16/2023] [Accepted: 04/03/2023] [Indexed: 04/09/2023]
Abstract
Yuquan Pill (YQP) is a traditional Chinese medicine (TCM) for the treatment of type 2 diabetes (T2DM) in China for many years, and has a beneficial clinical effect. In this study, the antidiabetic mechanism of YQP was investigated for the first time from the perspective of metabolomics and intestinal microbiota. After 28 days of high-fat feeding, rats were injected intraperitoneally with streptozotocin (STZ, 35 mg/kg) followed by a single oral administration of YQP 2.16 g/kg and metformin 200 mg/kg for 5 weeks. The results showed that YQP was effectively improved insulin resistance and alleviated hyperglycemia and hyperlipidemia associated with T2DM. YQP was found to regulate metabolism and gut microbiota in T2DM rats using untargeted metabolomics and gut microbiota integration. Forty-one metabolites and five metabolic pathways were identified, including Ascorbate and aldarate metabolism, Nicotinate and nicotinamide metabolism, Galactose metabolism, Pentose phosphate pathway and Tyrosine metabolism. YQP can regulate T2DM-induced dysbacteriosis by modulating the abundance of Firmicutes, Bacteroidetes, Ruminococcus, Lactobacillus. The restorative effects of YQP in rats with T2DM have been confirmed and provide a scientific basis for the clinical treatment of diabetic patients.
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Zhang J, Wu X, Zhong B, Liao Q, Wang X, Xie Y, He X. Review on the Diverse Biological Effects of Glabridin. Drug Des Devel Ther 2023; 17:15-37. [PMID: 36647530 PMCID: PMC9840373 DOI: 10.2147/dddt.s385981] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2022] [Accepted: 01/05/2023] [Indexed: 01/11/2023] Open
Abstract
Glabridin is a prenylated isoflavan from the roots of Glycyrrhiza glabra Linne and has posed great impact on the areas of drug development and medicine, due to various biological properties such as anti-inflammation, anti-oxidation, anti-tumor, anti-microorganism, bone protection, cardiovascular protection, neuroprotection, hepatoprotection, anti-obesity, and anti-diabetes. Many signaling pathways, including NF-κB, MAPK, Wnt/β-catenin, ERα/SRC-1, PI3K/AKT, and AMPK, have been implicated in the regulatory activities of glabridin. Interestingly, glabridin has been considered as an inhibitor of tyrosinase, P-glycoprotein (P-gp), and CYP2E1 and an activator of peroxisome proliferator-activated receptor γ (PPARγ), although their molecular regulating mechanisms still need further investigation. However, poor water solubility and low bioavailability have greatly limited the clinical applications of glabridin. Hopefully, several effective strategies, such as nanoemulsions, microneedles, and smartPearls formulation, have been developed for improvement.
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Affiliation(s)
- Jianhong Zhang
- Department of Hepatobiliary Surgery, First Affiliated Hospital of Gannan Medical University, Ganzhou, 341000, People’s Republic of China,Ganzhou Key Laboratory of Hepatocellular Carcinoma, First Affiliated Hospital of Gannan Medical University, Ganzhou, 341000, People’s Republic of China
| | - Xinhui Wu
- Department of General Surgery, The First Affiliated Hospital of Gannan Medical University, Ganzhou, 341000, People’s Republic of China
| | - Baiyin Zhong
- Department of Hepatobiliary Surgery, First Affiliated Hospital of Gannan Medical University, Ganzhou, 341000, People’s Republic of China
| | - Qicheng Liao
- Department of Hepatobiliary Surgery, First Affiliated Hospital of Gannan Medical University, Ganzhou, 341000, People’s Republic of China
| | - Xin Wang
- Department of Hepatobiliary Surgery, First Affiliated Hospital of Gannan Medical University, Ganzhou, 341000, People’s Republic of China
| | - Yuankang Xie
- Department of Hepatobiliary Surgery, First Affiliated Hospital of Gannan Medical University, Ganzhou, 341000, People’s Republic of China
| | - Xiao He
- Department of Hepatobiliary Surgery, First Affiliated Hospital of Gannan Medical University, Ganzhou, 341000, People’s Republic of China,Correspondence: Xiao He, Email
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Han X, Yang Y, Zhang M, Li L, Xue Y, Jia Q, Wang X, Guan S. Liquiritin Protects Against Cardiac Fibrosis After Myocardial Infarction by Inhibiting CCL5 Expression and the NF-κB Signaling Pathway. Drug Des Devel Ther 2022; 16:4111-4125. [PMID: 36483459 PMCID: PMC9724582 DOI: 10.2147/dddt.s386805] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/19/2022] [Accepted: 11/28/2022] [Indexed: 12/05/2022] Open
Abstract
Purpose Despite significant advances in interventional treatment, myocardial infarction (MI) and subsequent cardiac fibrosis remain major causes of high mortality worldwide. Liquiritin (LQ) is a flavonoid extract from licorice that possesses a variety of pharmacological properties. However, to our knowledge, the effects of LQ on myocardial fibrosis after MI have not been reported in detail. The aim of our research was to explore the potential role and mechanism of LQ in MI-induced myocardial damage. Methods The MI models were established by ligating the left anterior descending branch of the coronary artery. Next, rats were orally administered LQ once a day for 14 days. Biochemical assays, histopathological observations, ELISA, and Western blotting analyses were then conducted. Results LQ improved the heart appearance and ECG, decreased cardiac weight index and reduced levels of cardiac-specific markers such as CK, CK-MB, LDH, cTnI and BNP. Meanwhile, LQ reduced myocardial infarct size and improved hemodynamic parameters such as LVEDP, LVSP and ±dp/dtmax. Moreover, H&E staining showed that LQ attenuated the pathological damage caused by MI. Masson staining showed that LQ alleviated myocardial cell disorder and fibrosis while reducing collagen deposition. LQ also decreased the levels of oxidative stress and inflammation. Western blotting demonstrated that LQ significantly down-regulated the expressions of Collagen I, Collagen III, TGF-β1, MMP-9, α-SMA, CCL5, and p-NF-κB. Conclusion LQ protected against myocardial fibrosis following MI by improving cardiac function, and attenuating oxidative damage and inflammatory response, which may be associated with inhibition of CCL5 expression and the NF-κB pathway.
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Affiliation(s)
- Xue Han
- School of Pharmacy, Hebei University of Chinese Medicine, Shijiazhuang, People’s Republic of China
| | - Yakun Yang
- School of Pharmacy, Hebei University of Chinese Medicine, Shijiazhuang, People’s Republic of China
| | - Muqing Zhang
- College of Integrative Medicine, Hebei University of Chinese Medicine, Shijiazhuang, People’s Republic of China,Affiliated Hospital, Hebei University of Chinese Medicine, Shijiazhuang, People’s Republic of China
| | - Li Li
- School of Pharmacy, Hebei Medical University, Shijiazhuang, People’s Republic of China
| | - Yucong Xue
- College of Integrative Medicine, Hebei University of Chinese Medicine, Shijiazhuang, People’s Republic of China
| | - Qingzhong Jia
- School of Pharmacy, Hebei Medical University, Shijiazhuang, People’s Republic of China
| | - Xiangting Wang
- College of Integrative Medicine, Hebei University of Chinese Medicine, Shijiazhuang, People’s Republic of China,Hebei Key Laboratory of Integrative Medicine on Liver-Kidney Patterns, Shijiazhuang, People’s Republic of China,Correspondence: Xiangting Wang, College of Integrative Medicine, Hebei University of Chinese Medicine, Shijiazhuang, Hebei, People’s Republic of China, Email
| | - Shengjiang Guan
- Affiliated Hospital, Hebei University of Chinese Medicine, Shijiazhuang, People’s Republic of China,School of Basic Medicine, Hebei University of Chinese Medicine, Shijiazhuang, People’s Republic of China,Shengjiang Guan, Affiliated Hospital, Hebei University of Chinese Medicine, Shijiazhuang, Hebei, People’s Republic of China, Email
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Li T, Li X, Zhang J, Yu Z, Gong F, Wang J, Tang H, Xiang J, Zhang W, Cai D. Chemical component analysis of the traditional Chinese medicine Guipi Tang and its effects on major depressive disorder at molecular level. Heliyon 2022; 8:e12182. [DOI: 10.1016/j.heliyon.2022.e12182] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2022] [Revised: 11/21/2022] [Accepted: 11/30/2022] [Indexed: 12/14/2022] Open
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Kambale EK, Quetin-Leclercq J, Memvanga PB, Beloqui A. An Overview of Herbal-Based Antidiabetic Drug Delivery Systems: Focus on Lipid- and Inorganic-Based Nanoformulations. Pharmaceutics 2022; 14:2135. [PMID: 36297570 PMCID: PMC9610297 DOI: 10.3390/pharmaceutics14102135] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2022] [Revised: 09/29/2022] [Accepted: 10/05/2022] [Indexed: 11/05/2022] Open
Abstract
Diabetes is a metabolic pathology with chronic high blood glucose levels that occurs when the pancreas does not produce enough insulin or the body does not properly use the insulin it produces. Diabetes management is a puzzle and focuses on a healthy lifestyle, physical exercise, and medication. Thus far, the condition remains incurable; management just helps to control it. Its medical treatment is expensive and is to be followed for the long term, which is why people, especially from low-income countries, resort to herbal medicines. However, many active compounds isolated from plants (phytocompounds) are poorly bioavailable due to their low solubility, low permeability, or rapid elimination. To overcome these impediments and to alleviate the cost burden on disadvantaged populations, plant nanomedicines are being studied. Nanoparticulate formulations containing antidiabetic plant extracts or phytocompounds have shown promising results. We herein aimed to provide an overview of the use of lipid- and inorganic-based nanoparticulate delivery systems with plant extracts or phytocompounds for the treatment of diabetes while highlighting their advantages and limitations for clinical application. The findings from the reviewed works showed that these nanoparticulate formulations resulted in high antidiabetic activity at low doses compared to the corresponding plant extracts or phytocompounds alone. Moreover, it was shown that nanoparticulate systems address the poor bioavailability of herbal medicines, but the lack of enough preclinical and clinical pharmacokinetic and/or pharmacodynamic trials still delays their use in diabetic patients.
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Affiliation(s)
- Espoir K. Kambale
- Advanced Drug Delivery and Biomaterials Group, Louvain Drug Research Institute, UCLouvain, Université Catholique de Louvain, Avenue Mounier 73, B1.73.12, 1200 Brussels, Belgium
- Laboratory of Pharmaceutics and Phytopharmaceutical Drug Development, Faculty of Pharmaceutical Sciences, University of Kinshasa, B.P. 212, Kinshasa 012, Democratic Republic of the Congo
| | - Joëlle Quetin-Leclercq
- Pharmacognosy Research Group, Louvain Drug Research Institute, UCLouvain, Université Catholique de Louvain, Avenue Mounier 72, B1.72.03, 1200 Brussels, Belgium
| | - Patrick B. Memvanga
- Laboratory of Pharmaceutics and Phytopharmaceutical Drug Development, Faculty of Pharmaceutical Sciences, University of Kinshasa, B.P. 212, Kinshasa 012, Democratic Republic of the Congo
- Centre de Recherche et d’Innovation Technologique en Environnement et en Sciences de la Santé (CRITESS), University of Kinshasa, B.P. 212, Kinshasa 012, Democratic Republic of the Congo
| | - Ana Beloqui
- Advanced Drug Delivery and Biomaterials Group, Louvain Drug Research Institute, UCLouvain, Université Catholique de Louvain, Avenue Mounier 73, B1.73.12, 1200 Brussels, Belgium
- Walloon Excellence in Life Science and Biotechnology (WELBIO), Avenue Pasteur 6, 1300 Wavre, Belgium
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Discovery of quality markers for Mailuoshutong Pill based on “spider web” mode of “Content-Pharmacokinetics-Pharmacology” network. ARAB J CHEM 2022. [DOI: 10.1016/j.arabjc.2022.104296] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
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Tang TJ, Wang X, Wang L, Chen M, Cheng J, Zuo MY, Gu JF, Ding R, Zhou P, Huang JL. Liquiritin inhibits H 2 O 2 -induced oxidative stress injury in H9c2 cells via the AMPK/SIRT1/NF-κB signaling pathway. J Food Biochem 2022; 46:e14351. [PMID: 35929638 DOI: 10.1111/jfbc.14351] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2022] [Revised: 07/09/2022] [Accepted: 07/13/2022] [Indexed: 11/26/2022]
Abstract
Heart failure (HF) is a serious disease with high mortality. Oxidative stress plays a vital role in its occurrence and development. Licorice is commonly used to treat HF in traditional Chinese medicine. Liquiritin, the main ingredient of licorice, has antioxidant and anti-inflammatory properties, but the mechanism against oxidative stress in cardiomyocytes has not been reported. Establishment of oxidative damage model in H9c2 cells by hydrogen peroxide (H2 O2 ). Liquiritin (5, 10, 20 μmol/L) could significantly prevent the loss of cell viability and decrease the apoptosis rate. It can reduce the levels of reactive oxygen species (ROS), malonedialdehyde (MDA), lactate dehydrogenase (LDH), tumor necrosis factor-alpha (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6), and increase the activity of ATP, superoxidedismutase (SOD), glutathione peroxide (GSH-px), glutathione reductase (GR) and catalase (CAT) to alleviate oxidative stress and inflammation in a dose-dependent manner. Liquiritin was found to be related to AMP-Activated Protein Kinase (AMPK) pathway by molecular docking. Western blotting (WB) and quantitative reverse transcription PCR (RT-qPCR) confirmed that liquiritin could promote AMPKα phosphorylation and sirtuin 1 (SIRT1) protein expression, and inhibit phosphorylation of nuclear factor kappa B p65 (NF-κB p65). Compound C, EX 527, and PDTC can reverse the effects of liquiritin, indicating that its antioxidant effect is achieved by regulating AMPK/SIRT1/NF-κB signaling pathway. PRACTICAL APPLICATIONS: Heart failure is one of the most common cardiovascular diseases, and its treatment remains a worldwide problem. Licorice is a food and dietary supplement that has been used widely in traditional Chinese medicine (TCM). Liquiritin is one of the main active components of licorice, which has antioxidant and anti-inflammatory pharmacological effects. This study revealed the mechanism of licorice against oxidative damage of H9c2 cardiomyocytes, and provided a scientific basis for liquiritin as an antioxidant in the treatment of heart failure.
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Affiliation(s)
- Tong-Juan Tang
- Graduate School of Anhui University of Chinese Medicine, Hefei, China
| | | | - Liang Wang
- Department of Integrated Traditional Chinese and Western Medicine, Anhui University of Chinese Medicine, Hefei, China.,Research Institute of Integrated Traditional Chinese and Western Medicine, Anhui Academy of Chinese Medicine, Hefei, China.,Anhui Province Key Laboratory of Chinese Medicinal Formula, Anhui Academy of Chinese Medicine, Hefei, China
| | - Ming Chen
- Department of Integrated Traditional Chinese and Western Medicine, Anhui University of Chinese Medicine, Hefei, China.,Research Institute of Integrated Traditional Chinese and Western Medicine, Anhui Academy of Chinese Medicine, Hefei, China.,Anhui Province Key Laboratory of Chinese Medicinal Formula, Anhui Academy of Chinese Medicine, Hefei, China
| | - Jing Cheng
- School of Nursing, Anhui University of Chinese Medicine, Hefei, China
| | - Meng-Yu Zuo
- Graduate School of Anhui University of Chinese Medicine, Hefei, China
| | - Jin-Fan Gu
- Graduate School of Anhui University of Chinese Medicine, Hefei, China
| | - Rui Ding
- Graduate School of Anhui University of Chinese Medicine, Hefei, China
| | - Peng Zhou
- Department of Integrated Traditional Chinese and Western Medicine, Anhui University of Chinese Medicine, Hefei, China.,Research Institute of Integrated Traditional Chinese and Western Medicine, Anhui Academy of Chinese Medicine, Hefei, China.,Anhui Province Key Laboratory of Chinese Medicinal Formula, Anhui Academy of Chinese Medicine, Hefei, China
| | - Jin-Ling Huang
- Department of Integrated Traditional Chinese and Western Medicine, Anhui University of Chinese Medicine, Hefei, China.,Research Institute of Integrated Traditional Chinese and Western Medicine, Anhui Academy of Chinese Medicine, Hefei, China.,Anhui Province Key Laboratory of Chinese Medicinal Formula, Anhui Academy of Chinese Medicine, Hefei, China
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Molaei A, Molaei E, Sadeghnia H, Hayes AW, Karimi G. LKB1: An emerging therapeutic target for cardiovascular diseases. Life Sci 2022; 306:120844. [PMID: 35907495 DOI: 10.1016/j.lfs.2022.120844] [Citation(s) in RCA: 19] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/04/2022] [Revised: 07/22/2022] [Accepted: 07/24/2022] [Indexed: 10/16/2022]
Abstract
Cardiovascular diseases (CVDs) are currently the most common cause of morbidity and mortality worldwide. Experimental studies suggest that liver kinase B1 (LKB1) plays an important role in the heart. Several studies have shown that cardiomyocyte-specific LKB1 deletion leads to hypertrophic cardiomyopathy, left ventricular contractile dysfunction, and an increased risk of atrial fibrillation. In addition, the cardioprotective effects of several medicines and natural compounds, including metformin, empagliflozin, bexarotene, and resveratrol, have been reported to be associated with LKB1 activity. LKB1 limits the size of the damaged myocardial area by modifying cellular metabolism, enhancing the antioxidant system, suppressing hypertrophic signals, and inducing mild autophagy, which are all primarily mediated by the AMP-activated protein kinase (AMPK) energy sensor. LKB1 also improves myocardial efficiency by modulating the function of contractile proteins, regulating the expression of electrical channels, and increasing vascular dilatation. Considering these properties, stimulation of LKB1 signaling offers a promising approach in the prevention and treatment of heart diseases.
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Affiliation(s)
- Ali Molaei
- Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | | | - Hamidreza Sadeghnia
- Pharmacological Research Center of Medicinal Plants, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran; Department of Pharmacology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - A Wallace Hayes
- University of South Florida College of Public Health, Tampa, FL, USA
| | - Gholamreza Karimi
- Pharmaceutical Research Center, Institute of Pharmaceutical Technology, Mashhad University of Medical Sciences, Mashhad, Iran; Department of Pharmacodynamics and Toxicology, Faculty of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran..
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