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Yu H, Gachmaa B, Yu J, Tian-Liang, Uranghai X, Guo G, Xu W, Wang P, Liu J, Jukov A, Mandakh U, Ganbat D, Battseren T, Borjigidai A. A comprehensive and systemic review of the Gentiana: Ethnobotany, traditional applications, phytochemistry, pharmacology, and toxicology in the Mongolian Plateau. JOURNAL OF ETHNOPHARMACOLOGY 2025; 345:119573. [PMID: 40057145 DOI: 10.1016/j.jep.2025.119573] [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: 11/03/2024] [Revised: 02/08/2025] [Accepted: 02/28/2025] [Indexed: 03/15/2025]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Gentiana is the largest genus within the Gentianaceae family, comprising around 400 species that are widely distributed in temperate alpine regions worldwide, including the Mongolian Plateau. Despite their broad distribution, no comprehensive review on the distribution, ethnobotany, traditional uses, phytochemistry, pharmacology, and toxicology of Gentiana species in the Mongolian plateau. AIM This paper aims to provide the first detailed summary of Gentiana species distributed in the Mongolian Plateau, including those in Mongolia. It comprehensively addresses their botanical characteristics, traditional applications, phytochemistry, pharmacology, and toxicity, of Gentiana, providing a scientific basis for further research and identifying gaps in knowledge. MATERIALS AND METHODS Data were collected through a comprehensive survey of journal articles, books, and dissertations from databases such as Web of Science, ScienceDirect, Google Scholar, PubMed, Springer Link, CNKI, VIP, and Wan Fang Data. Additionally, online resources like Flora of China and Plants of the World Online were consulted for species distribution and scientific name verification. Phytochemical compounds were visualized using Chem Draw 14.0 software. RESULTS This review identifies twenty-nine Gentiana species distributed in the Mongolian Plateau, with nine species having documented folkloric uses for the treating digestive, skin, joint diseases, and sore throat, etc. Phytochemical studies have led to the isolation and identification of 602 compounds, including iridoids, triterpenoids, flavonoids, lignans, coumarins, xanthones, alkaloids, fatty acids, amino acids, organic acids, and polysaccharides. Notably, gentiopicroside (75) and swertiamarin (118) are the most studied monomeric compounds. Crude extracts of Gentiana show a broad spectrum of pharmacological activities, such as anti-inflammatory, analgesic, anti-bacterial, antioxidant, anti-tumor, anti-cancer, anti-diabetic, immunomodulatory, hepatoprotective, gastroprotective, neuroprotective, and joint and bone protective activities, etc. These extracts exhibit no apparent toxicity in vivo and in vitro studies. However, clinical research on the therapeutic applications of Gentiana remains limited. CONCLUSIONS This review provides the first comprehensive summary of Gentiana species from the Mongolian Plateau, covering their distribution, morphology, phytochemistry, traditional uses, and pharmacological activities. Compared to existing literature, it offers a more thorough taxa, emphasizing key bioactive compounds such as gentiopicroside and swertiamarin, which are recognized for their anti-inflammatory and hepatoprotective effects. The review also reveals the correlation between pharmacological activities and traditional applications. Furthermore, many Gentiana species remain underexplored, highlighting significant potential for future research and the development of therapeutic applications.
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Affiliation(s)
- Hongzhen Yu
- Key Laboratory of Ethnomedicine of Ministry of Education, Minzu University of China, Beijing, China
| | - Batzaya Gachmaa
- Botanical Garden and Research Institute, Mongolian Academy of Science, Ulaanbaatar, Mongolia
| | - Jiaoneng Yu
- Key Laboratory of Ethnomedicine of Ministry of Education, Minzu University of China, Beijing, China
| | - Tian-Liang
- Hainan Key Laboratory of Research and Development of Natural Product from Li Folk Medicine, Institute of Tropical Bioscience and Biotechnology, Chinese Academy of Tropical Agricultural Sciences, Haikou, 571101, China
| | - Xorgan Uranghai
- Key Laboratory of Ethnomedicine of Ministry of Education, Minzu University of China, Beijing, China
| | - Guangying Guo
- Key Laboratory of Ethnomedicine of Ministry of Education, Minzu University of China, Beijing, China
| | - Weiwei Xu
- Key Laboratory of Ethnomedicine of Ministry of Education, Minzu University of China, Beijing, China
| | - Ping Wang
- Institute of Chinese Materia Medica China Academy of Chinese Medical Sciences, Beijing, China
| | - Jinxin Liu
- Key Laboratory of Ethnomedicine of Ministry of Education, Minzu University of China, Beijing, China; China Academy of Medical Sciences, Peking Union Medical College Institute of Medicinal Plant Development, Beijing, China
| | - Azzaya Jukov
- Botanical Garden and Research Institute, Mongolian Academy of Science, Ulaanbaatar, Mongolia
| | - Urtnasan Mandakh
- Institute of Geography and Geoecology, Mongolian Academy of Sciences, Ulaanbaatar, Mongolia
| | - Danzanchadav Ganbat
- Institute of Geography and Geoecology, Mongolian Academy of Sciences, Ulaanbaatar, Mongolia; College of Geographical Science, Inner Mongolia Normal University, Hohhot, 010022, China
| | - Tsambaa Battseren
- Botanical Garden and Research Institute, Mongolian Academy of Science, Ulaanbaatar, Mongolia.
| | - Almaz Borjigidai
- Key Laboratory of Ethnomedicine of Ministry of Education, Minzu University of China, Beijing, China.
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Ma L, Chen Y, Yue R, Li Z, Wang Y, Bian Y, Wang M. Network pharmacology combined with metabolomics to reveal the anti-fibrotic mechanism of Polygoni Orientalis Fructus in CCl 4-induced hepatic fibrosis rats. J Proteomics 2024; 304:105227. [PMID: 38878880 DOI: 10.1016/j.jprot.2024.105227] [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: 04/10/2024] [Revised: 06/10/2024] [Accepted: 06/11/2024] [Indexed: 06/24/2024]
Abstract
Polygoni Orientalis Fructus (POF), a dried ripe fruit of Polygonum orientale L., is commonly used in China for liver disease treatment. However, its therapeutic mechanism remains unclear. The aim of this study was to elucidate the effects of POF on the regulation of endogenous metabolites and identify its key therapeutic targets in hepatic fibrosis (HF) rats by integrating network pharmacology and metabolomics approaches. First, serum liver indices and histopathological analyses were used to evaluate the therapeutic effects of POF on carbon tetrachloride (CCl4)-induced HF. Subsequently, differential metabolites and potential therapeutic targets of POF were screened using plasma metabolomics and network pharmacology, respectively. The key targets of POF were identified by overlapping differential metabolite-associated targets with the potential targets and validated by molecular docking and ELISA experiments. The results showed that POF effectively alleviated HF in rats. A total of 51 metabolites related to HF were screened, and 24 were associated with POF. 232 potential therapeutic targets were identified by network pharmacology analysis. Finally, six key targets were identified through a combined analysis. Furthermore, molecular docking and ELISA validation revealed that AGXT, PAH, and NOS3 are targets of POF action, while CBS, ALDH2, and ARG1 were identified as potential targets. SIGNIFICANCE: POF is now commonly used in the treatment of liver disease, but its mechanism of action remains unclear. Current studies on metabolomics of liver disease primarily focuse on the interpretation of differential metabolites and related metabolic pathways. This research delves into the intricate details of metabolomics findings via network pharmacology to uncover the targets and pathways of drug action.
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Affiliation(s)
- Lizhou Ma
- School of Life Science and Biopharmaceutics, Shenyang Pharmaceutical University, Wenhua Road 103, Shenyang, Liaoning 110016, China
| | - Yu Chen
- School of Life Science and Biopharmaceutics, Shenyang Pharmaceutical University, Wenhua Road 103, Shenyang, Liaoning 110016, China
| | - Rong Yue
- School of Life Science and Biopharmaceutics, Shenyang Pharmaceutical University, Wenhua Road 103, Shenyang, Liaoning 110016, China
| | - Ziyu Li
- School of Pharmacy, Shenyang Pharmaceutical University, Wenhua Road 103, Shenyang, Liaoning 110016, China
| | - Yibo Wang
- School of Pharmacy, Shenyang Pharmaceutical University, Wenhua Road 103, Shenyang, Liaoning 110016, China
| | - Yanggang Bian
- School of Life Science and Biopharmaceutics, Shenyang Pharmaceutical University, Wenhua Road 103, Shenyang, Liaoning 110016, China
| | - Miao Wang
- School of Life Science and Biopharmaceutics, Shenyang Pharmaceutical University, Wenhua Road 103, Shenyang, Liaoning 110016, China.
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Zheng W, Shi C, Meng Y, Peng J, Zhou Y, Pan T, Ning K, Xie Q, Xiang H. Integrated network analysis and metabolomics reveal the molecular mechanism of Yinchen Sini decoction in CCl 4-induced acute liver injury. Front Pharmacol 2023; 14:1221046. [PMID: 37818184 PMCID: PMC10561237 DOI: 10.3389/fphar.2023.1221046] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2023] [Accepted: 09/11/2023] [Indexed: 10/12/2023] Open
Abstract
Objective: Yinchen Sini decoction (YCSND), a traditional Chinese medicine (TCM) formula, plays a crucial role in the treatment of liver disease. However, the bioactive constituents and pharmacological mechanisms of action remain unclear. The present study aimed to reveal the molecular mechanism of YCSND in the treatment of acute liver injury (ALI) using integrated network analysis and metabolomics. Methods: Ultra-high-performance liquid chromatography coupled with Q-Exactive focus mass spectrum (UHPLC-QE-MS) was utilized to identify metabolites in YCSND, and high-performance liquid chromatography (HPLC) was applied to evaluate the quality of four botanical drugs in YCSND. Cell damage and ALI models in mice were established using CCl4. 1H-NMR metabolomics approach, along with histopathological observation using hematoxylin and eosin (H&E), biochemical measurements, and reverse transcription quantitative real-time PCR (RT-qPCR), was applied to evaluate the effect of YCSND on CCl4- induced ALI. Network analysis was conducted to predict the potential targets of YCSND in ALI. Result: Our results showed that 89 metabolites in YCSND were identified using UHPLC-QE-MS. YCSND protected against ALI by reducing the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and malondialdehyde (MDA) contents and increasing those of superoxide dismutase (SOD), and glutathione (GSH) both in vivo and in vitro. The 1H-NMRmetabolic pattern revealed that YCSND reversed CCl4-induced metabolic abnormalities in the liver. Additionally, the Kyoto Encyclopedia of Genes and Genome (KEGG) pathway enrichment analysis identified five pathways related to liver injury, including the PI3K-AKT, MAPK, HIF-1, apoptosis, and TNF signaling pathways. Moreover, RT-qPCR showed YCSND regulated the inflammatory response (Tlr4, Il6, Tnfα, Nfκb1, Ptgs2, and Mmp9) and apoptosis (Bcl2, Caspase3, Bax, and Mapk3), and inhibited PI3K-AKT signaling pathway (Pi3k and Akt1). Combined network analysis and metabolomics showed a link between the key targets (Tlr4, Ptgs2, and Mmp9) and vital metabolites (choline, xanthine, lactate, and 3-hydroxybutyric acid) of YCSND in ALI. Conclusion: Overall, the results contribute to the understanding of the therapeutic effects of YCSND on ALI, and indicate that the integrated network analysis and metabolomics could be a powerful strategy to reveal the pharmacological effects of TCM.
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Affiliation(s)
- Weiwei Zheng
- Key Laboratory for Molecular Enzymology and Engineering of Ministry of Education, School of Life Sciences, Jilin University, Changchun, Jilin, China
| | - Chao Shi
- Key Laboratory for Molecular Enzymology and Engineering of Ministry of Education, School of Life Sciences, Jilin University, Changchun, Jilin, China
| | - Yao Meng
- Key Laboratory for Molecular Enzymology and Engineering of Ministry of Education, School of Life Sciences, Jilin University, Changchun, Jilin, China
| | - Jian Peng
- Key Laboratory for Molecular Enzymology and Engineering of Ministry of Education, School of Life Sciences, Jilin University, Changchun, Jilin, China
| | - Yongfei Zhou
- Key Laboratory for Molecular Enzymology and Engineering of Ministry of Education, School of Life Sciences, Jilin University, Changchun, Jilin, China
| | - Tong Pan
- Key Laboratory for Molecular Enzymology and Engineering of Ministry of Education, School of Life Sciences, Jilin University, Changchun, Jilin, China
| | - Ke Ning
- Key Laboratory for Molecular Enzymology and Engineering of Ministry of Education, School of Life Sciences, Jilin University, Changchun, Jilin, China
| | - Qiuhong Xie
- Key Laboratory for Molecular Enzymology and Engineering of Ministry of Education, School of Life Sciences, Jilin University, Changchun, Jilin, China
- National Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University, Changchun, Jilin, China
- Institute of Changbai Mountain Resource and Health, Jilin University, Fusong, Jilin, China
| | - Hongyu Xiang
- Key Laboratory for Molecular Enzymology and Engineering of Ministry of Education, School of Life Sciences, Jilin University, Changchun, Jilin, China
- National Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University, Changchun, Jilin, China
- Institute of Changbai Mountain Resource and Health, Jilin University, Fusong, Jilin, China
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Effect of Gypenosides on the composition of gut microbiota and metabolic activity in the treatment of CCl4-induced liver injury in rats. J Funct Foods 2022. [DOI: 10.1016/j.jff.2022.105233] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022] Open
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Martin-Grau M, Marrachelli VG, Monleon D. Rodent models and metabolomics in non-alcoholic fatty liver disease: What can we learn? World J Hepatol 2022; 14:304-318. [PMID: 35317178 PMCID: PMC8891675 DOI: 10.4254/wjh.v14.i2.304] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/25/2021] [Revised: 04/13/2021] [Accepted: 01/29/2022] [Indexed: 02/06/2023] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) prevalence has increased drastically in recent decades, affecting up to 25% of the world’s population. NAFLD is a spectrum of different diseases that starts with asymptomatic steatosis and continues with development of an inflammatory response called steatohepatitis, which can progress to fibrosis. Several molecular and metabolic changes are required for the hepatocyte to finally vary its function; hence a “multiple hit” hypothesis seems a more accurate proposal. Previous studies and current knowledge suggest that in most cases, NAFLD initiates and progresses through most of nine hallmarks of the disease, although the triggers and mechanisms for these can vary widely. The use of animal models remains crucial for understanding the disease and for developing tools based on biological knowledge. Among certain requirements to be met, a good model must imitate certain aspects of the human NAFLD disorder, be reliable and reproducible, have low mortality, and be compatible with a simple and feasible method. Metabolism studies in these models provides a direct reflection of the workings of the cell and may be a useful approach to better understand the initiation and progression of the disease. Metabolomics seems a valid tool for studying metabolic pathways and crosstalk between organs affected in animal models of NAFLD and for the discovery and validation of relevant biomarkers with biological understanding. In this review, we provide a brief introduction to NAFLD hallmarks, the five groups of animal models available for studying NAFLD and the potential role of metabolomics in the study of experimental NAFLD.
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Affiliation(s)
- Maria Martin-Grau
- Department of Pathology, University of Valencia, Valencia 46010, Spain
| | - Vannina G Marrachelli
- Department of Physiology, University of Valencia, Valencia 46010, Spain
- Health Research Institute INCLIVA, Valencia 46010, Spain
| | - Daniel Monleon
- Department of Pathology, University of Valencia, Valencia 46010, Spain
- Health Research Institute INCLIVA, Valencia 46010, Spain
- CIBER de Fragilidad y Envejecimiento Saludable (CIBERfes), Madrid 28029, Spain
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Ammar NM, Hassan HA, Abdallah HMI, Afifi SM, Elgamal AM, Farrag ARH, El-Gendy AENG, Farag MA, Elshamy AI. Protective Effects of Naringenin from Citrus sinensis (var. Valencia) Peels against CCl 4-Induced Hepatic and Renal Injuries in Rats Assessed by Metabolomics, Histological and Biochemical Analyses. Nutrients 2022; 14:841. [PMID: 35215494 PMCID: PMC8924893 DOI: 10.3390/nu14040841] [Citation(s) in RCA: 25] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2021] [Revised: 02/10/2022] [Accepted: 02/14/2022] [Indexed: 02/07/2023] Open
Abstract
Citrus fruits are grown worldwide for their special nutritive and several health benefits. Among citrus bioactives, naringenin, a major flavanone, exhibits a potential hepatoprotective effect that is not fully elucidated. Herein, serum biochemical parameters and histopathological assays were used to estimate the hepatoprotective activity of naringenin, isolated from Citrus sinensis (var. Valencia) peels, in CCl4-induced injury in a rat model. Further, GC-MS-based untargeted metabolomics was used to characterize the potential metabolite biomarkers associated with its activity. Present results revealed that naringenin could ameliorate the increases in liver enzymes (ALT and AST) induced by CCl4 and attenuate the pathological changes in liver tissue. Naringenin decreased urea, creatinine and uric acid levels and improved the kidney tissue architecture, suggesting its role in treating renal disorders. In addition, naringenin increased the expression of the antiapoptoic cell marker, Bcl-2. Significant changes in serum metabolic profiling were noticed in the naringenin-treated group compared to the CCl4 group, exemplified by increases in palmitic acid, stearic acid, myristic acid and lauric acids and decrease levels of alanine, tryptophan, lactic acid, glucosamine and glucose in CCl4 model rats. The results suggested that naringenin's potential hepato- and renoprotective effects could be related to its ability to regulate fatty acids (FAs), amino acids and energy metabolism, which may become effective targets for liver and kidney toxicity management. In conclusion, the current study presents new insights into the hepato- and renoprotective mechanisms of naringenin against CCl4-induced toxicity.
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Affiliation(s)
- Naglaa M. Ammar
- Therapeutic Chemistry Department, Pharmaceutical and Drugs Research Institute, National Research Centre, Giza 12622, Egypt; (N.M.A.); (H.A.H.)
| | - Heba A. Hassan
- Therapeutic Chemistry Department, Pharmaceutical and Drugs Research Institute, National Research Centre, Giza 12622, Egypt; (N.M.A.); (H.A.H.)
| | - Heba M. I. Abdallah
- Pharmacology Department, Medical Research and Clinical Studies Institute, National Research Centre, Giza 12622, Egypt;
| | - Sherif M. Afifi
- Pharmacognosy Department, Faculty of Pharmacy, University of Sadat City, Sadat City 32897, Egypt;
| | - Abdelbaset M. Elgamal
- Chemistry of Microbial and Natural Products Department, Pharmaceutical and Drugs Research Institute, National Research Centre, Giza 12622, Egypt;
| | - Abdel Razik H. Farrag
- Department of Pathology, Medical Research and Clinical Studies Institute, National Research Centre, Giza 12622, Egypt;
| | - Abd El-Nasser G. El-Gendy
- Medicinal and Aromatic Plants Research Department, Pharmaceutical and Drugs Research Institute, National Research Centre, Cairo 12622, Egypt;
| | - Mohamed A. Farag
- Pharmacognosy Department, College of Pharmacy, Cairo University, Cairo 11562, Egypt;
- School of Forestry and Biotechnology, Zhejiang A&F University, Hangzhou 311300, China
| | - Abdelsamed I. Elshamy
- Chemistry of Natural Compounds Department, Pharmaceutical and Drugs Research Institute, National Research Centre, Giza 12622, Egypt
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Cao H, Xi S, He W, Ma X, Liu L, Xu J, Zhang K, Li Y, Jin L. The effects of Gentiana dahurica Fisch on alcoholic liver disease revealed by RNA sequencing. JOURNAL OF ETHNOPHARMACOLOGY 2021; 279:113422. [PMID: 33007391 DOI: 10.1016/j.jep.2020.113422] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/19/2020] [Revised: 08/22/2020] [Accepted: 09/25/2020] [Indexed: 05/26/2023]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE The root of Gentiana dahurica Fisch (called Qin-Jiao in China), a traditional Chinese medicine, is used in China to treat alcoholic liver disease (ALD), but there has been no scientific report on the treatment of ALD. AIM OF THE STUDY To investigate the therapeutic effects of Gentiana dahurica Fisch ethanol extract (GDEE) on ALD and to reveal its possible mechanism of action using RNA sequencing. MATERIALS AND METHODS The model of ALD was established by continuous gavage with alcohol in mice, and GDEE was used to treat ALD. Pathological observation (HE staining, oil red O staining) and biochemical indicators were performed to evaluate liver tissue lesions and efficacy of GDEE. RNA sequencing analysis of liver tissues was carried out to elucidate the pathogenesis of ALD and the mechanism of hepatoprotective effect by GDEE. The RNA sequencing results were verified by detecting mRNA and protein expressions of acetyl coenzyme A carboxylase α (Acacα), fatty acid synthase (Fasn) and carnitine palmitoyltransferase 1A (Cpt1a) by quantitative real-time polymerase chain reaction (PCR) and Western blot. RESULTS Measurements of biochemical parameters showed that GDEE could inhibit the increased transaminase activities in the serum and lipid levels in the liver caused by alcohol. It was observed that GDEE could alleviate fatty degeneration, edema and cell necrosis caused by alcohol in the liver tissue. RNA sequencing analysis of liver tissues found that 719 genes and 1137 genes were significantly changed by alcohol and GDEE, respectively. GDEE reversed most of the changes in triglycerides synthesis-related genes up-regulated by alcohol. GDEE up-regulated most of the genes involved in the fatty acid degradation in ALD mice, while alcohol had little effect on them. In addition, GDEE suppressed most of the genes involved in cholesterol synthesis that were up-regulated by alcohol. GDEE up-regulated genes related to bile acid synthesis in ALD mice, and down-regulated genes related to bile acid reabsorption, while alcohol had no significant effect on genes related to bile acid metabolism. In the validation experiments, the Acacα, Fasn and Cpt1a expressions quantified by real-time PCR and Western blot were consistent with the RNA sequencing results. CONCLUSIONS GDEE can alleviate liver damage and steatosis in ALD mice, and its mechanism of action may be related to the process of regulating triglycerides and cholesterol.
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Affiliation(s)
- Houkang Cao
- College of Pharmacy, Gansu University of Chinese Medicine, Lanzhou, Gansu, 730000, PR China.
| | - Shaoyang Xi
- College of Pharmacy, Gansu University of Chinese Medicine, Lanzhou, Gansu, 730000, PR China.
| | - Weiwei He
- College of Pharmacy, Gansu University of Chinese Medicine, Lanzhou, Gansu, 730000, PR China.
| | - Xiaohui Ma
- College of Pharmacy, Gansu University of Chinese Medicine, Lanzhou, Gansu, 730000, PR China.
| | - Li Liu
- College of Pharmacy, Gansu University of Chinese Medicine, Lanzhou, Gansu, 730000, PR China.
| | - Jie Xu
- College of Pharmacy, Guilin Medical University, Guilin, Guangxi, 541004, PR China.
| | - Kefeng Zhang
- College of Pharmacy, Guilin Medical University, Guilin, Guangxi, 541004, PR China.
| | - Yingdong Li
- College of Integration of Chinese and Western Medicine, Gansu University of Chinese Medicine, Lanzhou, Gansu, 730000, PR China.
| | - Ling Jin
- College of Pharmacy, Gansu University of Chinese Medicine, Lanzhou, Gansu, 730000, PR China.
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Zhang Y, Zhao M, Liu Y, Liu T, Zhao C, Wang M. Investigation of the therapeutic effect of Yinchen Wuling Powder on CCl 4-induced hepatic fibrosis in rats by 1H NMR and MS-based metabolomics analysis. J Pharm Biomed Anal 2021; 200:114073. [PMID: 33873073 DOI: 10.1016/j.jpba.2021.114073] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/06/2021] [Revised: 03/27/2021] [Accepted: 04/10/2021] [Indexed: 02/06/2023]
Abstract
Hepatic fibrosis (HF) is a typical consequence of various chronic liver diseases, and there is still no ideal drug for its treatment. Yinchen Wuling Powder (YCWLP), a famous traditional Chinese medicine prescription, is effective for the treatment of icteric hepatitis, hepatic fibrosis, non-alcoholic fatty liver disease and other liver diseases in clinical practices, however, the underlying mechanisms of YCWLP on HF is still unclear. In this study, 1H NMR and MS-based metabolomics analysis along with body weight change, serum liver function indexes, serum liver fibrosis index and histopathological observations of liver were applied to evaluate the therapeutic effect of YCWLP on hepatic fibrosis and the mechanism associated with this. The results of the pharmacodynamics study show that YCWLP has a significant therapeutic effect on hepatic fibrosis. As for the metabolomics research, 7 metabolites in the plasma samples, 28 in the urine samples and 6 in the liver samples were significantly altered due to the protective effect of YCWLP on CCl4-induced hepatic fibrosis. These endogenous metabolites are involved in amino acid metabolism, carbohydrate metabolism, glycerophospholipid metabolism and gut bacteria metabolism. These findings suggest that YCWLP could treat hepatic fibrosis by promoting urea circulation and reducing blood ammonia accumulation, improving carbohydrate metabolism and reducing oxidative stress, improving glycerophospholipid metabolism and protecting cell membrane, and regulating intestinal flora metabolism.
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Affiliation(s)
- Yumeng Zhang
- School of Pharmacy, Shenyang Pharmaceutical University, Wenhua Road 103, Shenyang, Liaoning, China
| | - Min Zhao
- School of Pharmacy, Shenyang Pharmaceutical University, Wenhua Road 103, Shenyang, Liaoning, China
| | - Yangyang Liu
- School of Life Science and Biopharmaceutics, Shenyang Pharmaceutical University, Wenhua Road 103, Shenyang, Liaoning, China
| | - Tingting Liu
- School of Pharmacy, Shenyang Pharmaceutical University, Wenhua Road 103, Shenyang, Liaoning, China
| | - Chunjie Zhao
- School of Pharmacy, Shenyang Pharmaceutical University, Wenhua Road 103, Shenyang, Liaoning, China.
| | - Miao Wang
- School of Life Science and Biopharmaceutics, Shenyang Pharmaceutical University, Wenhua Road 103, Shenyang, Liaoning, China.
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Rosli NHM, Yahya HM, Ibrahim FW, Shahar S, Ismail IS, Azam AA, Rajab NF. Serum Metabolomics Profiling of Commercially Mixed Functional Foods—Effects in Beta-Amyloid Induced Rats Measured Using 1H NMR Spectroscopy. Nutrients 2020; 12:nu12123812. [PMID: 33322743 PMCID: PMC7764480 DOI: 10.3390/nu12123812] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2020] [Revised: 12/04/2020] [Accepted: 12/09/2020] [Indexed: 11/16/2022] Open
Abstract
Functional foods such as pomegranate, dates and honey were shown by various previous studies to individually have a neuroprotective effect, especially in neurodegenerative disease such as Alzheimer’s disease (AD). In this novel and original study, an 1H NMR spectroscopy tool was used to identify the metabolic neuroprotective mechanism of commercially mixed functional foods (MFF) consisting of pomegranate, dates and honey, in rats injected with amyloid-beta 1-42 (Aβ-42). Forty-five male albino Wistar rats were randomly divided into five groups: NC (0.9% normal saline treatment + phosphate buffer solution (PBS) solution injection), Abeta (0.9% normal saline treatment + 0.2 µg/µL Aβ-42 injection), MFF (4 mL/kg MFF treatment + PBS solution injection), Abeta–MFF (4 mL/kg MFF treatment + 0.2 µg/µL Aβ-42 injection) and Abeta–NAC (150 mg/kg N-acetylcysteine + 0.2 µg/µL Aβ-42 injection). Based on the results, the MFF and NAC treatment improved the spatial memory and learning using Y-maze. In the metabolic analysis, a total of 12 metabolites were identified, for which levels changed significantly among the treatment groups. Systematic metabolic pathway analysis found that the MFF and NAC treatments provided a neuroprotective effect in Aβ-42 injected rats by improving the acid amino and energy metabolisms. Overall, this finding showed that MFF might serve as a potential neuroprotective functional food for the prevention of AD.
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Affiliation(s)
- Nur Hasnieza Mohd Rosli
- Biomedical Science Program, Faculty of Health Sciences, Universiti Kebangsaan Malaysia, Jalan Raja Muda Abdul Aziz, Kuala Lumpur 50300, Malaysia;
| | - Hanis Mastura Yahya
- Centre for Healthy Aging and Wellness (H-Care), Faculty of Health Sciences, Universiti Kebangsaan Malaysia, Jalan Raja Muda Abdul Aziz, Kuala Lumpur 50300, Malaysia; (H.M.Y.); (S.S.)
| | - Farah Wahida Ibrahim
- Centre for Toxicology and Health Risk Studies (CORE), Faculty of Health Sciences, Universiti Kebangsaan Malaysia, Jalan Raja Muda Abdul Aziz, Kuala Lumpur 50300, Malaysia;
| | - Suzana Shahar
- Centre for Healthy Aging and Wellness (H-Care), Faculty of Health Sciences, Universiti Kebangsaan Malaysia, Jalan Raja Muda Abdul Aziz, Kuala Lumpur 50300, Malaysia; (H.M.Y.); (S.S.)
| | - Intan Safinar Ismail
- Laboratory of Natural Products, Institute of Bioscience, Universiti Putra Malaysia, Serdang 43400, Selangor, Malaysia; (I.S.I.); (A.A.A.)
| | - Amalina Ahmad Azam
- Laboratory of Natural Products, Institute of Bioscience, Universiti Putra Malaysia, Serdang 43400, Selangor, Malaysia; (I.S.I.); (A.A.A.)
| | - Nor Fadilah Rajab
- Centre for Healthy Aging and Wellness (H-Care), Faculty of Health Sciences, Universiti Kebangsaan Malaysia, Jalan Raja Muda Abdul Aziz, Kuala Lumpur 50300, Malaysia; (H.M.Y.); (S.S.)
- Correspondence: ; Tel.: +60-3-9289-7002
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Effect of Defatted Dabai Pulp Extract in Urine Metabolomics of Hypercholesterolemic Rats. Nutrients 2020; 12:nu12113511. [PMID: 33202660 PMCID: PMC7697915 DOI: 10.3390/nu12113511] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/16/2020] [Revised: 11/08/2020] [Accepted: 11/12/2020] [Indexed: 12/17/2022] Open
Abstract
A source of functional food can be utilized from a source that might otherwise be considered waste. This study investigates the hypocholesterolemic effect of defatted dabai pulp (DDP) from supercritical carbon dioxide extraction and the metabolic alterations associated with the therapeutic effects of DDP using 1H NMR urinary metabolomic analysis. Male-specific pathogen-free Sprague-Dawley rats were fed with a high cholesterol diet for 30 days to induce hypercholesterolemia. Later, the rats were administered with a 2% DDP treatment diet for another 30 days. Supplementation with the 2% DDP treatment diet significantly reduced the level of total cholesterol (TC), triglyceride, low-density lipoprotein (LDL), and inflammatory markers (C-reactive protein (CRP), interleukin 6 (IL6) and tumour necrosis factor-α (α-TNF)) and significantly increased the level of antioxidant profile (total antioxidant status (TAS), superoxide dismutase (SOD), glutathione peroxide (GPX), and catalase (CAT)) compared with the positive control group (PG) group (p < 0.05). The presence of high dietary fibre (28.73 ± 1.82 g/100 g) and phenolic compounds (syringic acid, 4-hydroxybenzoic acid and gallic acid) are potential factors contributing to the beneficial effect. Assessment of 1H NMR urinary metabolomics revealed that supplementation of 2% of DDP can partially recover the dysfunction in the metabolism induced by hypercholesterolemia via choline metabolism. 1H-NMR-based metabolomic analysis of urine from hypercholesterolemic rats in this study uncovered the therapeutic effect of DDP to combat hypercholesterolemia.
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Beyoğlu D, Idle JR. Metabolomic insights into the mode of action of natural products in the treatment of liver disease. Biochem Pharmacol 2020; 180:114171. [DOI: 10.1016/j.bcp.2020.114171] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/04/2020] [Revised: 07/19/2020] [Accepted: 07/20/2020] [Indexed: 02/08/2023]
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Li X, Wang X, Hong D, Zeng S, Su J, Fan G, Zhang Y. Metabolic Discrimination of Different Rhodiola Species Using 1H-NMR and GEP Combinational Chemometrics. Chem Pharm Bull (Tokyo) 2019; 67:81-87. [DOI: 10.1248/cpb.c18-00509] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Affiliation(s)
- Xuanhao Li
- School of Ethnic Medicine, Chengdu University of Traditional Chinese Medicine
| | - Xiaobo Wang
- School of Ethnic Medicine, Chengdu University of Traditional Chinese Medicine
| | - Daoxin Hong
- School of Ethnic Medicine, Chengdu University of Traditional Chinese Medicine
| | - Shangyu Zeng
- School of Ethnic Medicine, Chengdu University of Traditional Chinese Medicine
| | - Jinsong Su
- School of Ethnic Medicine, Chengdu University of Traditional Chinese Medicine
| | - Gang Fan
- School of Ethnic Medicine, Chengdu University of Traditional Chinese Medicine
| | - Yi Zhang
- School of Ethnic Medicine, Chengdu University of Traditional Chinese Medicine
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