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Zhang C, Zhu Y, Wang M, Chen R, Sun X. Comparison of chemical composition between imitation wild and transplanted Astragali Radix and their therapeutic effects on heart failure. JOURNAL OF ETHNOPHARMACOLOGY 2025; 337:118827. [PMID: 39293703 DOI: 10.1016/j.jep.2024.118827] [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: 06/29/2024] [Revised: 08/25/2024] [Accepted: 09/12/2024] [Indexed: 09/20/2024]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Astragali Radix (AR) is a traditional Chinese herbal medicine, which has been widely used on treating chronic heart failure (CHF) in clinical practice. Two main types of AR in the market are the imitation wild AR (5YAR) and transplanted AR (2YAR). It remains unclear whether there are variations in the anti-heart failure effects of AR with different growth years. Further research is required to explore the material composition and mechanisms of AR in combating heart failure. AIM OF THE STUDY The aim of the study was to compare the main chemical composition content and the protective effects of 2YAR and 5YAR on heart failure. MATERIALS AND METHODS Ethanol extracts of 2YAR and 5YAR were prepared, and chemical composition analysis was conducted. C57BL/6 mice were subcutaneously injected with ISO to induce heart failure (HF) and were administrated with a corresponding dose of the extracts of 2YAR and 5YAR by gavage for 28 days. Cardiac function was evaluated using echocardiography. The serum levels of enzymes related to myocardial injury, oxidative stress, and inflammation were detected. The left ventricle was excised for hematoxylin-eosin, Masson, Sirius Red, wheat germ agglutinin, and TUNEL staining. Electron microscopy examination of mitochondrial structure in myocardial cells. Protein expression of monocarboxylate transporter 4 (MCT4), Peroxisome proliferator-activated receptor-γ coactivator 1α (PGC-1α), phosphorylated AMP-activated protein kinase (p-AMPK), phosphorylated serine/threonine protein kinase (p-AKT), and phosphorylated insulin receptor substrates 1 (p-IRS-1) were detected by immunohistochemistry and Western blot. RESULTS The content of saponins and flavonoids in 5YAR was higher than that in the 2YAR. However, the content of polysaccharides in 5YAR is lower than in 2YAR. The treatment of 2YAR and 5YAR daily for 28 days prevented ISO-induced myocardial damage, including the decrease in serum cardiac enzymes and cardiomyocyte apoptotic index, and improvement in heart function and mitochondrial structure. Additionally, 2YAR and 5YAR reduced serum inflammatory factors and myocardial fibrosis levels. Treatment with 2YAR and 5YAR also decreased MCT4 expression and enhanced PGC-1α, p-AKT, p-AMPK, and p-IRS-1 expression in heart tissues. CONCLUSIONS The 5YAR was better than 2YAR in anti-heart failure, which may be related to the increase in saponins and flavonoids content. AR exerts anti-heart failure effect by improving mitochondrial function and ameliorating cardiac insulin resistance through activation of the AMPK/PGC1α and IRS/AKT pathways.
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Affiliation(s)
- Chongyang Zhang
- Institute of Medicinal Plant Development, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China; School of Chinese Materia Medica, Guangdong Pharmaceutical University, Guangzhou, China
| | - Yindi Zhu
- Academy of Chinese Materia Medica, Wenzhou Medical University, Wenzhou, China
| | - Min Wang
- Institute of Medicinal Plant Development, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China; Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Ministry of Education, Beijing, China; Institute of Medicinal Plant Development, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing Key Laboratory of Innovative Drug Discovery of Traditional Chinese Medicine (Natural Medicine) and Translational Medicine, Beijing, China
| | - Rongchang Chen
- Institute of Medicinal Plant Development, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China; Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Ministry of Education, Beijing, China; Institute of Medicinal Plant Development, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing Key Laboratory of Innovative Drug Discovery of Traditional Chinese Medicine (Natural Medicine) and Translational Medicine, Beijing, China.
| | - Xiaobo Sun
- Institute of Medicinal Plant Development, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China; Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Ministry of Education, Beijing, China; Institute of Medicinal Plant Development, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing Key Laboratory of Innovative Drug Discovery of Traditional Chinese Medicine (Natural Medicine) and Translational Medicine, Beijing, China.
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Lu Z, Fu Y, Fu Q, Chang Y, Zhang M, Jin T. Ginsenoside RG3 Synergizes With STING Agonist to Reverse Cisplatin Resistance in Gastric Cancer. Food Sci Nutr 2025; 13:e4744. [PMID: 39834553 PMCID: PMC11745231 DOI: 10.1002/fsn3.4744] [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: 04/25/2024] [Revised: 12/17/2024] [Accepted: 12/23/2024] [Indexed: 01/22/2025] Open
Abstract
This study investigates the synergistic inhibitory effects of combining the stimulator of interferon genes (STING) agonist cyclic diadenylate monophosphate (c-di-AMP) and ginsenoside RG3 on cisplatin (DDP)-resistant gastric cancer (GC) cells. The objective is to identify novel therapeutic targets and offers insights for the clinical management of DDP resistance. Various techniques were employed, including western blot, MTT assay, colony formation assay, scratch assay, transwell assay, tubule formation assay, flow cytometry, Hoechst 33342 fluorescence staining, and in vivo experiments, to investigate the potential mechanisms and effects of the combined application of the STING agonist and ginsenoside RG3 in reversing cisplatin resistance in gastric cancer. The combination markedly suppressed key malignant behaviors, including proliferation, migration, invasion, and angiogenesis of SGC-7901/DDP cells. Additionally, this treatment inhibited the epithelial-mesenchymal transition (EMT) process and stem cell-like characteristics of SGC-7901/DDP cells, while downregulating the expression of resistance-related proteins. The STING agonist effectively suppresses the growth and proliferation of gastric cancer cells. Ginsenoside RG3, well-documented for its multifaceted properties, including antioxidant, anti-aging, and anti-cancer effects, is widely used in cancer treatment and in managing chemotherapy-related side effects. Furthermore, RG3 enhances anti-tumor immunity by regulating signal transduction. This study comprehensively evaluated the efficacy of the STING agonist and RG3 combination through in vitro and in vivo experiments, demonstrating significant inhibition of malignant progression and reversal of drug resistance in gastric cancer. These findings offer a robust theoretical foundation for clinical applications and highlight new therapeutic targets for future research.
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Affiliation(s)
- Zhongqi Lu
- Department of Central LaboratoryYanbian University HospitalYanjiChina
- Key Laboratory of the Science and Technology Department of Jilin ProvinceYanjiChina
- Department of Ultrasound MedicineShaanxi Provincial People's HospitalXi'AnShaanxiChina
| | - Yihang Fu
- Department of Central LaboratoryYanbian University HospitalYanjiChina
- Key Laboratory of the Science and Technology Department of Jilin ProvinceYanjiChina
| | - Qiang Fu
- Department of Central LaboratoryYanbian University HospitalYanjiChina
- Key Laboratory of the Science and Technology Department of Jilin ProvinceYanjiChina
- Department of Ultrasound MedicineYanbian University HospitalYanjiJilinChina
| | - Ying Chang
- Department of Central LaboratoryYanbian University HospitalYanjiChina
- Key Laboratory of the Science and Technology Department of Jilin ProvinceYanjiChina
- Department of Ultrasound MedicineYanbian University HospitalYanjiJilinChina
| | - Meihua Zhang
- Department of Central LaboratoryYanbian University HospitalYanjiChina
- Department of Ultrasound MedicineYanbian University HospitalYanjiJilinChina
- Department of Health Examination CentreYanbian University HospitalYanjiChina
| | - Tiefeng Jin
- Department of Central LaboratoryYanbian University HospitalYanjiChina
- Key Laboratory of the Science and Technology Department of Jilin ProvinceYanjiChina
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Zhang J, Li N, Hu X. Metabolic Reprograming of Macrophages: A New Direction in Traditional Chinese Medicine for Treating Liver Failure. J Immunol Res 2024; 2024:5891381. [PMID: 39741958 PMCID: PMC11688140 DOI: 10.1155/jimr/5891381] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2023] [Revised: 09/03/2024] [Accepted: 11/28/2024] [Indexed: 01/03/2025] Open
Abstract
Acute liver failure (ALF) is a fulminant clinical syndrome that usually leads to multiple organ failure and high mortality. Macrophages play a crucial role in the initiation, development, and recovery of ALF. Targeting macrophages through immunotherapy holds significant promise as a therapeutic strategy. These cells exhibit remarkable plasticity, enabling them to differentiate into various subtypes based on changes in their surrounding microenvironment. M1-type macrophages are associated with a pro-inflammatory phenotype and primarily rely predominantly on glycolysis. In contrast, M2-type macrophages, which are characterized by anti-inflammatory phenotype, predominantly obtain their energy from oxidative phosphorylation (OXPHOS) and fatty acid oxidation (FAO). Shifting macrophage metabolism from glycolysis to OXPHOS inhibits M1 macrophage activation and promotes M2 macrophage activation, thereby exerting anti-inflammatory and reparative effects. This study elucidates the relationship between macrophage activation and glucose metabolism reprograming from an immunometabolism perspective. A comprehensive literature review revealed that several signaling pathways may regulate macrophage polarization through energy metabolism, including phosphatidyl-inositol 3-kinase/protein kinase B (PI3K/AKT), mammalian target of rapamycin (mTOR)/hypoxia-inducible factor 1α (HIF-1α), nuclear factor-κB (NF-κB), and AMP-activated protein kinase (AMPK), which exhibit crosstalk with one another. Additionally, we systematically reviewed several traditional Chinese medicine (TCM) monomers that can modulate glucose metabolism reprograming and influence the polarization states of M1 and M2 macrophages. This review aimed to provide valuable insights that could contribute to the development of new therapies or drugs for ALF.
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Affiliation(s)
- Junli Zhang
- Department of Infectious Diseases, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, China
- Department of Clinical Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Na Li
- Department of Infectious Diseases, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, China
- Department of Clinical Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Xiaoyu Hu
- Department of Infectious Diseases, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, China
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Zhou Z, Li M, Zhang Z, Song Z, Xu J, Zhang M, Gong M. Overview of Panax ginseng and its active ingredients protective mechanism on cardiovascular diseases. JOURNAL OF ETHNOPHARMACOLOGY 2024; 334:118506. [PMID: 38964625 DOI: 10.1016/j.jep.2024.118506] [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: 03/11/2024] [Revised: 06/25/2024] [Accepted: 06/27/2024] [Indexed: 07/06/2024]
Abstract
ETHNIC PHARMACOLOGICAL RELEVANCE Panax ginseng is a traditional Chinese herbal medicine used to treat cardiovascular diseases (CVDs), and it is still widely used to improve the clinical symptoms of various CVDs. However, there is currently a lack of summary and analysis on the mechanism of Panax ginseng exerts its cardiovascular protective effects. This article provides a review of in vivo and in vitro pharmacological studies on Panax ginseng and its active ingredients in reducing CVDs damage. AIM OF THIS REVIEW This review summarized the latest literature on Panax ginseng and its active ingredients in CVDs research, aiming to have a comprehensive and in-depth understanding of the cardiovascular protection mechanism of Panax ginseng, and to provide new ideas for the treatment of CVDs, as well as to optimize the clinical application of Panax ginseng. METHODS Enrichment of pathways and biological terms using the traditional Chinese medicine molecular mechanism bioinformatics analysis tool (BATMAN-TCM). The literature search is based on electronic databases such as PubMed, ScienceDirect, Scopus, CNKI, with a search period of 2002-2023. The search terms include Panax ginseng, Panax ginseng ingredients, ginsenosides, ginseng polysaccharides, ginseng glycoproteins, ginseng volatile oil, CVDs, heart, and cardiac. RESULTS 132 articles were ultimately included in the review. The ingredients in Panax ginseng that manifested cardiovascular protective effects are mainly ginsenosides (especially ginsenoside Rb1). Ginsenosides protected against CVDs such as ischemic reperfusion injury, atherosclerosis and heart failure mainly through improving energy metabolism, inhibiting hyper-autophagy, antioxidant, anti-inflammatory and promoting secretion of exosomes. CONCLUSION Panax ginseng and its active ingredients have a particularly prominent effect on improving myocardial energy metabolism remodeling in protecting against CVDs. The AMPK and PPAR signaling pathways are the key targets through which Panax ginseng produces multiple mechanisms of cardiovascular protection. Extracellular vesicles and nanoparticles as carriers are potential delivery ways for optimizing the bioavailability of Panax ginseng and its active ingredients.
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Affiliation(s)
- Ziwei Zhou
- School of Traditional Chinese Medicine, Capital Medical University, Beijing, 100069, China
| | - Meijing Li
- School of Traditional Chinese Medicine, Capital Medical University, Beijing, 100069, China
| | - Zekuan Zhang
- School of Traditional Chinese Medicine, Capital Medical University, Beijing, 100069, China
| | - Zhimin Song
- School of Traditional Chinese Medicine, Capital Medical University, Beijing, 100069, China
| | - Jingjing Xu
- School of Traditional Chinese Medicine, Capital Medical University, Beijing, 100069, China; Beijing Key Laboratory of Traditional Chinese Medicine Collateral Disease Theory Research, Beijing, 100069, China
| | - Minyu Zhang
- School of Traditional Chinese Medicine, Capital Medical University, Beijing, 100069, China; Beijing Key Laboratory of Traditional Chinese Medicine Collateral Disease Theory Research, Beijing, 100069, China.
| | - Muxin Gong
- School of Traditional Chinese Medicine, Capital Medical University, Beijing, 100069, China; Beijing Key Laboratory of Traditional Chinese Medicine Collateral Disease Theory Research, Beijing, 100069, China.
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Zhao Y, Wang X, Teng H, Zhao T, Nadembega WMC, Fan X, Zhang W, Fan B, Chi Y, Zhao Y, Liu S. Weighted Gene Co-Expression Network Based on Transcriptomics: Unravelling the Differentiation Dynamics of 3T3-L1 Preadipocytes and the Regulatory Mechanism of Protopanaxatriol. Int J Mol Sci 2024; 25:12254. [PMID: 39596321 PMCID: PMC11594308 DOI: 10.3390/ijms252212254] [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: 09/29/2024] [Revised: 11/06/2024] [Accepted: 11/12/2024] [Indexed: 11/28/2024] Open
Abstract
The intricate regulatory mechanisms governing adipocyte differentiation are pivotal in elucidating the complex pathophysiology underlying obesity. This study aims to explore the dynamic changes in gene expression during the differentiation of 3T3-L1 adipocytes using transcriptomics methods. Protopanaxatriol (PPT) significantly inhibited adipocyte differentiation. To uncover the molecular mechanisms, we conducted an extensive transcriptomic analysis of adipocytes throughout various differentiation stages, comparing gene expression profiles before and after PPT treatment. The construction of 16 co-expression modules was achieved using weighted gene co-expression network analysis (WGCNA). The 838 differentially expressed genes in the blue module were highly correlated with PPT treatment. Further analysis revealed that PIKfyve, STAT3, JAK1, CTTN, TYK2, JAK3, STAT2, STAT5b, SOCS3, and IRF9 were core genes closely associated with adipocyte differentiation. This discovery underscores the potential pivotal function of these ten genes in regulating adipocyte differentiation. This study elucidated that PPT, an active ingredient in ginseng, could reduce lipid accumulation by inhibiting the differentiation of adipocyte precursors through the negative regulation of genes such as PIKfyve, STAT3, and JAK1. Finally, molecular docking identified potential binding sites for PPT on PIKfyve and JAK1. This study provides potential drug targets for preventing obesity and related metabolic diseases.
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Affiliation(s)
- Yaru Zhao
- College of Chinese Medicinal Materials, Jilin Agricultural University, Changchun 130117, China; (Y.Z.); (X.W.); (H.T.); (X.F.); (W.Z.); (B.F.); (Y.C.)
- International Joint Laboratory for Development of Animal and Plant Resources for Food and Medicine, Changchun 130118, China; (T.Z.); (W.M.C.N.)
| | - Xv Wang
- College of Chinese Medicinal Materials, Jilin Agricultural University, Changchun 130117, China; (Y.Z.); (X.W.); (H.T.); (X.F.); (W.Z.); (B.F.); (Y.C.)
- International Joint Laboratory for Development of Animal and Plant Resources for Food and Medicine, Changchun 130118, China; (T.Z.); (W.M.C.N.)
| | - Hongbo Teng
- College of Chinese Medicinal Materials, Jilin Agricultural University, Changchun 130117, China; (Y.Z.); (X.W.); (H.T.); (X.F.); (W.Z.); (B.F.); (Y.C.)
- International Joint Laboratory for Development of Animal and Plant Resources for Food and Medicine, Changchun 130118, China; (T.Z.); (W.M.C.N.)
| | - Tianyi Zhao
- International Joint Laboratory for Development of Animal and Plant Resources for Food and Medicine, Changchun 130118, China; (T.Z.); (W.M.C.N.)
| | - Wendyam Marie Christelle Nadembega
- International Joint Laboratory for Development of Animal and Plant Resources for Food and Medicine, Changchun 130118, China; (T.Z.); (W.M.C.N.)
| | - Xinhua Fan
- College of Chinese Medicinal Materials, Jilin Agricultural University, Changchun 130117, China; (Y.Z.); (X.W.); (H.T.); (X.F.); (W.Z.); (B.F.); (Y.C.)
- International Joint Laboratory for Development of Animal and Plant Resources for Food and Medicine, Changchun 130118, China; (T.Z.); (W.M.C.N.)
| | - Wenxin Zhang
- College of Chinese Medicinal Materials, Jilin Agricultural University, Changchun 130117, China; (Y.Z.); (X.W.); (H.T.); (X.F.); (W.Z.); (B.F.); (Y.C.)
- International Joint Laboratory for Development of Animal and Plant Resources for Food and Medicine, Changchun 130118, China; (T.Z.); (W.M.C.N.)
| | - Bowen Fan
- College of Chinese Medicinal Materials, Jilin Agricultural University, Changchun 130117, China; (Y.Z.); (X.W.); (H.T.); (X.F.); (W.Z.); (B.F.); (Y.C.)
- International Joint Laboratory for Development of Animal and Plant Resources for Food and Medicine, Changchun 130118, China; (T.Z.); (W.M.C.N.)
| | - Yuye Chi
- College of Chinese Medicinal Materials, Jilin Agricultural University, Changchun 130117, China; (Y.Z.); (X.W.); (H.T.); (X.F.); (W.Z.); (B.F.); (Y.C.)
| | - Yan Zhao
- College of Chinese Medicinal Materials, Jilin Agricultural University, Changchun 130117, China; (Y.Z.); (X.W.); (H.T.); (X.F.); (W.Z.); (B.F.); (Y.C.)
- International Joint Laboratory for Development of Animal and Plant Resources for Food and Medicine, Changchun 130118, China; (T.Z.); (W.M.C.N.)
| | - Shuangli Liu
- College of Chinese Medicinal Materials, Jilin Agricultural University, Changchun 130117, China; (Y.Z.); (X.W.); (H.T.); (X.F.); (W.Z.); (B.F.); (Y.C.)
- International Joint Laboratory for Development of Animal and Plant Resources for Food and Medicine, Changchun 130118, China; (T.Z.); (W.M.C.N.)
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Liu L, Jin M, Han X, Dou D. Identifying biomarkers of ginseng medicines with different natures on heart failure. JOURNAL OF ETHNOPHARMACOLOGY 2024; 329:118134. [PMID: 38574777 DOI: 10.1016/j.jep.2024.118134] [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: 12/02/2023] [Revised: 03/22/2024] [Accepted: 03/28/2024] [Indexed: 04/06/2024]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE The nature of Chinese medicine is a unique index to measure its efficacy. Generally, treating the hot syndrome with cold nature medicine and vice versa. Ginseng medicines, a renowned Chinese medicine known for its qi tonifying action, encompasses various herbal materials such as ginseng, red ginseng, and black ginseng (GS, RG, and BG, respectively), ginseng leaves (GL), and American ginseng (AG), which exhibited different natures, thought contained similar ginsenosides. This traditional effect of GS and RG "reinvigorate the pulse for relieving qi depletion". It is closely linked to anti-heart failure (HF), HF is a clinical manifestation of deficiency of "heart-qi". However, the elucidation of the mechanism underlying the anti-HF effects of ginseng medicines with different natures remains a significant challenge. AIM OF THE STUDY To elucidate pharmacological mechanisms underlying the effect of ginseng medicines on HF, and to identify biomarkers associated with their various natures. Furthermore, it provides the basis for the different applications of ginseng medicines with various natures. MATERIALS AND METHODS This study established a rat model of HF induced by isoproterenol (ISO) combined with a specific diet. Four representative hot/cold herbs were selected as compared references for the medicine natures. The divergent effects of these herbs on the HF model were investigated by analyzing RNA-seq data to identify genes expressed differentially. Additionally, pathways associated with medicine natures were obtained using KEGG. Furthermore, UPLC-QqQ-MS/MS, as well as ELISA, were used to measure indexes associated with the nervous system, energy metabolisms, and endocrinology systems, such as BNP, CK, IL-1, T3, T4, cAMP, cGMP, AD, adrenal hormones (DOC, CORT, and COR), progestogens (pregnenolone, P, 17-OH-PR, and 17-OH-P), androgens (DHEA, A4, and T), and estrogens hormones (E2). RESULTS All ginseng medicines demonstrated varying levels of efficacy in alleviating HF and GS exhibited a significant protective effect on HF. The ginseng medicines with qi tonifying primarily achieve their effect by enhancing the levels of adrenal hormones (DOC, CORT, and COR), T4, elevation of cAMP/cGMP, and activation of AchE. Warm nature qi tonifying ginseng medicines increased the levels of 17-OH-PR and P while decreasing 17-OH-P and the ratio of E2/T. On the other hand, cold nature qi tonifying ginseng medicines decreased the levels of A4 and T while increasing the ratio of E2/T. CONCLUSION Overall, the effects of warm nature ginseng medicines are stronger on HF compared to cold nature ginseng medicines. Our research firstly reported that the E2/T ratio, progestogens (17-OH-PR, 17-OH-P, and P), and androgens (A4 and T) have been identified as significant biomarkers for discerning the mechanism differences of ginseng medicines with differences natures in treatment of HF.
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Affiliation(s)
- Linlin Liu
- College of Pharmacy, Liaoning University of Traditional Chinese Medicine, Dalian, China
| | - Mozhu Jin
- College of Pharmacy, Liaoning University of Traditional Chinese Medicine, Dalian, China
| | - Xueying Han
- College of Pharmacy, Liaoning University of Traditional Chinese Medicine, Dalian, China
| | - Deqiang Dou
- College of Pharmacy, Liaoning University of Traditional Chinese Medicine, Dalian, China.
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Feng F, Ko HA, Truong TMT, Song WJ, Ko EJ, Kang I. Ginsenoside Rg3, enriched in red ginseng extract, improves lipopolysaccharides-induced suppression of brown and beige adipose thermogenesis with mitochondrial activation. Sci Rep 2024; 14:9157. [PMID: 38644456 PMCID: PMC11033271 DOI: 10.1038/s41598-024-59758-1] [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: 07/09/2023] [Accepted: 04/15/2024] [Indexed: 04/23/2024] Open
Abstract
Brown adipose tissue (BAT) which is a critical regulator of energy homeostasis, and its activity is inhibited by obesity and low-grade chronic inflammation. Ginsenoside Rg3, the primary constituent of Korean red ginseng (steamed Panax ginseng CA Meyer), has shown therapeutic potential in combating inflammatory and metabolic diseases. However, it remains unclear whether Rg3 can protect against the suppression of browning or activation of BAT induced by inflammation. In this study, we conducted a screening of ginsenoside composition in red ginseng extract (RGE) and explored the anti-adipogenic effects of both RGE and Rg3. We observed that RGE (exist 0.25 mg/mL of Rg3) exhibited significant lipid-lowering effects in adipocytes during adipogenesis. Moreover, treatment with Rg3 (60 μM) led to the inhibition of triglyceride accumulation, subsequently promoting enhanced fatty acid oxidation, as evidenced by the conversion of radiolabeled 3H-fatty acids into 3H-H2O with mitochondrial activation. Rg3 alleviated the attenuation of browning in lipopolysaccharide (LPS)-treated beige adipocytes and primary brown adipocytes by recovered by uncoupling protein 1 (UCP1) and the oxygen consumption rate compared to the LPS-treated group. These protective effects of Rg3 on inflammation-induced inhibition of beige and BAT-derived thermogenesis were confirmed in vivo by treating with CL316,243 (a beta-adrenergic receptor agonist) and LPS to induce browning and inflammation, respectively. Consistent with the in vitro data, treatment with Rg3 (2.5 mg/kg, 8 weeks) effectively reversed the LPS-induced inhibition of brown adipocyte features in C57BL/6 mice. Our findings confirm that Rg3-rich foods are potential browning agents that counteract chronic inflammation and metabolic complications.
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Affiliation(s)
- Fang Feng
- Department of Food Science and Nutrition, Jeju National University, Jeju, 63243, Korea
| | - Hyun-A Ko
- Department of Food Science and Nutrition, Jeju National University, Jeju, 63243, Korea
| | - Thi My Tien Truong
- Interdisciplinary Graduate Program in Advanced Convergence Technology and Science, Jeju National University, Jeju, 63243, Korea
| | - Woo-Jin Song
- College of Veterinary Medicine, Jeju National University, Jeju, 63243, Korea
| | - Eun-Ju Ko
- Interdisciplinary Graduate Program in Advanced Convergence Technology and Science, Jeju National University, Jeju, 63243, Korea
- College of Veterinary Medicine, Jeju National University, Jeju, 63243, Korea
| | - Inhae Kang
- Department of Food Science and Nutrition, Jeju National University, Jeju, 63243, Korea.
- Interdisciplinary Graduate Program in Advanced Convergence Technology and Science, Jeju National University, Jeju, 63243, Korea.
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Liu X, Gu J, Wang C, Peng M, Zhou J, Fei X, Zhong Z, Li B. Ginsenoside Rg3 attenuates neuroinflammation and hippocampal neuronal damage after traumatic brain injury in mice by inactivating the NF-kB pathway via SIRT1 activation. Cell Cycle 2024; 23:662-681. [PMID: 38796716 PMCID: PMC11229723 DOI: 10.1080/15384101.2024.2355008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2023] [Revised: 03/24/2024] [Accepted: 05/07/2024] [Indexed: 05/28/2024] Open
Abstract
This investigation examined the potential of ginsenoside Rg3 in addressing traumatic brain injury (TBI). A TBI mouse model underwent treatment with ginsenoside Rg3 and nicotinamide (NAM). Neurological and motor functions were assessed using modified neurological severity score and rotarod tests. Brain water content in mice was detected. Primary mouse microglia were exposed to lipopolysaccharide (LPS), ginsenoside Rg3, and NAM. Nissl and immunofluorescence staining were utilized to investigate hippocampal damage, and localization of P65, Iba1 and INOS in microglia. Hippocampal neurons were grown in a culture medium derived from microglia. CCK-8 and TUNEL assays were employed to evaluate the viability and apoptosis of hippocampal neurons. Proinflammatory factors and proteins were tested using ELISA, western blot and immunofluorescence staining. As a result, ginsenoside Rg3 enhanced neurological and motor functions in mice post-TBI, reduced brain water content, alleviated hippocampal neuronal neuroinflammation and damage, activated SIRT1, and deactivated the NF-kB pathway. In LPS-stimulated microglia, ginsenoside Rg3 diminished inflammation, activated SIRT1, deactivated the NF-kB pathway, and facilitated nuclear localization of P65 and co-localization of Iba1 and INOS. The effects of ginsenoside Rg3 were countered by NAM in both TBI mice and LPS-stimulated microglia. Hippocampal neurons cultured in a medium containing LPS, ginsenoside Rg3, and NAM-treated microglia showed improved viability and reduced apoptosis compared to those cultured in a medium with LPS and ginsenoside Rg3-treated microglia alone. Ginsenoside Rg3 was effective in reducing neuroinflammation and damage in hippocampal neurons following TBI by modulating the SIRT1/NF-kB pathway, suggesting its potential as a therapeutic agent for TBI.
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Affiliation(s)
- Xi Liu
- Department of Neurosurgery, Changsha of Traditional Chinese Medicine Hospital, Changsha, Hunan, China
| | - Jia Gu
- Hunan International Scientific and Technological Cooperation Base of Brain Tumor Research, Xiangya Hospital, Central South University, Changsha, Hunan, China
| | - Cheng Wang
- Department of Neurosurgery, Changsha of Traditional Chinese Medicine Hospital, Changsha, Hunan, China
| | - Min Peng
- Department of Neurosurgery, Changsha of Traditional Chinese Medicine Hospital, Changsha, Hunan, China
| | - Jilin Zhou
- Department of Neurosurgery, Changsha of Traditional Chinese Medicine Hospital, Changsha, Hunan, China
| | - Xiyun Fei
- Department of Neurosurgery, Changsha of Traditional Chinese Medicine Hospital, Changsha, Hunan, China
| | - Zhijun Zhong
- Department of Neurosurgery, Changsha of Traditional Chinese Medicine Hospital, Changsha, Hunan, China
| | - Bo Li
- Department of Thoracic Surgery, Changsha of Traditional Chinese Medicine Hospital, Changsha, Hunan, China
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Shi L, Luo J, Wei X, Xu X, Tu L. The protective role of ginsenoside Rg3 in heart diseases and mental disorders. Front Pharmacol 2024; 15:1327033. [PMID: 38469409 PMCID: PMC10926849 DOI: 10.3389/fphar.2024.1327033] [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: 10/24/2023] [Accepted: 02/07/2024] [Indexed: 03/13/2024] Open
Abstract
Ginsenoside Rg3, a compound derived from Panax ginseng C. A. Mey., is increasingly recognized for its wide range of pharmacological effects. Under the worldwide healthcare challenges posed by heart diseases, Rg3 stands out as a key subject in modern research on Chinese herbal medicine, offering a novel approach to therapy. Mental illnesses are significant contributors to global disease mortality, and there is a well-established correlation between cardiac and psychiatric conditions. This connection is primarily due to dysfunctions in the sympathetic-adrenomedullary system (SAM), the hypothalamic-pituitary-adrenal axis, inflammation, oxidative stress, and brain-derived neurotrophic factor impairment. This review provides an in-depth analysis of Rg3's therapeutic benefits and its pharmacological actions in treating cardiac and mental health disorders respectively. Highlighting its potential for the management of these conditions, Rg3 emerges as a promising, multifunctional therapeutic agent.
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Affiliation(s)
- Lili Shi
- Department of Geriatric Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Hubei Key Laboratory of Genetics and Molecular Mechanisms of Cardiological Disorders, Wuhan, China
| | - Jinlan Luo
- Department of Geriatric Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Hubei Key Laboratory of Genetics and Molecular Mechanisms of Cardiological Disorders, Wuhan, China
| | - Xiupan Wei
- Department of Rehabilitation Medicine, Zhongda Hospital, Southeast University, Nanjing, China
| | - Xizhen Xu
- Hubei Key Laboratory of Genetics and Molecular Mechanisms of Cardiological Disorders, Wuhan, China
- Division of Cardiology and Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Ling Tu
- Department of Geriatric Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Hubei Key Laboratory of Genetics and Molecular Mechanisms of Cardiological Disorders, Wuhan, China
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Chen C, Wang J, Zhu X, Hu J, Liu C, Liu L. Energy metabolism and redox balance: How phytochemicals influence heart failure treatment. Biomed Pharmacother 2024; 171:116136. [PMID: 38215694 DOI: 10.1016/j.biopha.2024.116136] [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: 10/11/2023] [Revised: 12/31/2023] [Accepted: 01/04/2024] [Indexed: 01/14/2024] Open
Abstract
Heart Failure (HF) epitomizes a formidable global health quandary characterized by marked morbidity and mortality. It has been established that severe derangements in energy metabolism are central to the pathogenesis of HF, culminating in an inadequate cardiac energy milieu, which, in turn, precipitates cardiac pump dysfunction and systemic energy metabolic failure, thereby steering the trajectory and potential recuperation of HF. The conventional therapeutic paradigms for HF predominantly target amelioration of heart rate, and cardiac preload and afterload, proffering symptomatic palliation or decelerating the disease progression. However, the realm of therapeutics targeting the cardiac energy metabolism remains largely uncharted. This review delineates the quintessential characteristics of cardiac energy metabolism in healthy hearts, and the metabolic aberrations observed during HF, alongside the associated metabolic pathways and targets. Furthermore, we delve into the potential of phytochemicals in rectifying the redox disequilibrium and the perturbations in energy metabolism observed in HF. Through an exhaustive analysis of recent advancements, we underscore the promise of phytochemicals in modulating these pathways, thereby unfurling a novel vista on HF therapeutics. Given their potential in orchestrating cardiac energy metabolism, phytochemicals are emerging as a burgeoning frontier for HF treatment. The review accentuates the imperative for deeper exploration into how these phytochemicals specifically intervene in cardiac energy metabolism, and the subsequent translation of these findings into clinical applications, thereby broadening the horizon for HF treatment modalities.
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Affiliation(s)
- Cong Chen
- Guang'anmen Hospital, China Academy of Chinese Medicine Sciences, Beijing 100053, China
| | - Jie Wang
- Guang'anmen Hospital, China Academy of Chinese Medicine Sciences, Beijing 100053, China.
| | - Xueying Zhu
- Department of Anatomy, School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 102488, China
| | - Jun Hu
- Guang'anmen Hospital, China Academy of Chinese Medicine Sciences, Beijing 100053, China
| | - Chao Liu
- Guang'anmen Hospital, China Academy of Chinese Medicine Sciences, Beijing 100053, China
| | - Lanchun Liu
- Guang'anmen Hospital, China Academy of Chinese Medicine Sciences, Beijing 100053, China
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Li XC, Li FF, Pei WJ, Yang J, Gu YL, Piao XL. The Content and Principle of the Rare Ginsenosides Produced from Gynostemma pentaphyllum after Heat Treatment. Molecules 2023; 28:6415. [PMID: 37687242 PMCID: PMC10490127 DOI: 10.3390/molecules28176415] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2023] [Revised: 08/14/2023] [Accepted: 08/31/2023] [Indexed: 09/10/2023] Open
Abstract
Ginsenoside Rg3, Rk1, and Rg5, rare ginsenosides from Panax ginseng, have many pharmacological effects, which have attracted extensive attention. They can be obtained through the heat treatment of Gynostemma pentaphyllum. In this study, scanning electron microscopy (SEM) and thermal gravity-differential thermal gravity (TG-DTG) were employed to investigate this process and the content change in ginsenosides was analyzed using liquid chromatography-mass spectrometry (LC-MS). SEM and TG-DTG were used to compare the changes in the ginsenosides before and after treatment. In SEM, the presence of hydrogen bond rearrangement was indicated by the observed deformation of vascular bundles and ducts. The before-and-after changes in the peak patterns and peaks values in TG-DTG indicated that the content of different kinds of compounds produced changes, which all revealed that the formation of new saponins before and after the heat treatment was due to the breakage or rearrangement of chemical bonds. Additionally, the deformation of vascular bundles and vessels indicated the presence of hydrogen bond rearrangement. The glycosidic bond at the 20 positions could be cleaved by ginsenoside Rb3 to form ginsenoside Rd, which, in turn, gave rise to ginsenoside Rg3(S) and Rg3(R). They were further dehydrated to form ginsenoside Rk1 and Rg5. This transformation process occurs in a weak acidic environment provided by G. pentaphyllum itself, without the involvement of endogenous enzymes. In addition, the LC-MS analysis results showed that the content of ginsenoside Rb3 decreased from 2.25 mg/g to 1.80 mg/g, while the contents of ginsenoside Rk1 and Rg5 increased from 0.08 and 0.01 mg/g to 3.36 and 3.35 mg/g, respectively. Ginsenoside Rg3(S) and Rg3(R) were almost not detected in G. pentaphyllum, and the contents of them increased to 0.035 and 0.23 mg/g after heat treatment. Therefore, the rare ginsenosides Rg3(S), Rg3(R), Rk1, and Rg5 can be obtained from G. pentaphyllum via heat treatment.
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Affiliation(s)
| | | | | | | | - Yu-Long Gu
- School of Pharmacy, Minzu University of China, Beijing 100081, China; (X.-C.L.)
| | - Xiang-Lan Piao
- School of Pharmacy, Minzu University of China, Beijing 100081, China; (X.-C.L.)
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Kim J, Zhang S, Zhu Y, Wang R, Wang J. Amelioration of colitis progression by ginseng-derived exosome-like nanoparticles through suppression of inflammatory cytokines. J Ginseng Res 2023; 47:627-637. [PMID: 37720571 PMCID: PMC10499592 DOI: 10.1016/j.jgr.2023.01.004] [Citation(s) in RCA: 37] [Impact Index Per Article: 18.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2022] [Revised: 11/10/2022] [Accepted: 01/05/2023] [Indexed: 01/09/2023] Open
Abstract
Background Damage to the healthy intestinal epithelial layer and regulation of the intestinal immune system, closely interrelated, are considered pivotal parts of the curative treatment for inflammatory bowel disease (IBD). Plant-based diets and phytochemicals can support the immune microenvironment in the intestinal epithelial barrier for a balanced immune system by improving the intestinal microecological balance and may have therapeutic potential in colitis. However, there have been only a few reports on the therapeutic potential of plant-derived exosome-like nanoparticles (PENs) and the underlying mechanism in colitis. This study aimed to assess the therapeutic effect of PENs from Panax ginseng, ginseng-derived exosome-like nanoparticles (GENs), in a mouse model of IBD, with a focus on the intestinal immune microenvironment. Method To evaluate the anti-inflammatory effect of GENs on acute colitis, we treated GENs in Caco2 and lipopolysaccharide (LPS) -induced RAW 264.7 macrophages and analyzed the gene expression of pro-inflammatory cytokines and anti-inflammatory cytokines such as TNF-α, IL-6, and IL-10 by real-time PCR (RT-PCR). Furthermore, we further examined bacterial DNA from feces and determined the alteration of gut microbiota composition in DSS-induced colitis mice after administration of GENs through 16S rRNA gene sequencing analysis. Result GENs with low toxicity showed a long-lasting intestinal retention effect for 48 h, which could lead to effective suppression of pro-inflammatory cytokines such as TNF-α and IL-6 production through inhibition of NF-κB in DSS-induced colitis. As a result, it showed longer colon length and suppressed thickening of the colon wall in the mice treated with GENs. Due to the amelioration of the progression of DSS-induced colitis with GENs treatment, the prolonged survival rate was observed for 17 days compared to 9 days in the PBS-treated group. In the gut microbiota analysis, the ratio of Firmicutes/Bacteroidota was decreased, which means GENs have therapeutic effectiveness against IBD. Ingesting GENs would be expected to slow colitis progression, strengthen the gut microbiota, and maintain gut homeostasis by preventing bacterial dysbiosis. Conclusion GENs have a therapeutic effect on colitis through modulation of the intestinal microbiota and immune microenvironment. GENs not only ameliorate the inflammation in the damaged intestine by downregulating pro-inflammatory cytokines but also help balance the microbiota on the intestinal barrier and thereby improve the digestive system.
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Affiliation(s)
- Jisu Kim
- Department of Pharmaceutics, School of Pharmacy, Fudan University & Key Laboratory of Smart Drug Delivery, Ministry of Education, Shanghai, China
| | - Shuya Zhang
- Department of Pharmaceutics, School of Pharmacy, Fudan University & Key Laboratory of Smart Drug Delivery, Ministry of Education, Shanghai, China
| | - Ying Zhu
- Department of Integrative Oncology, Fudan University Shanghai Cancer Center, Shanghai, China
| | - Ruirui Wang
- Shanghai Innovation Center of TCM Health Service, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Jianxin Wang
- Department of Pharmaceutics, School of Pharmacy, Fudan University & Key Laboratory of Smart Drug Delivery, Ministry of Education, Shanghai, China
- Institutes of Integrative Medicine, Fudan University, Shanghai, China
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Wang X, Gao Y, Zhang J, Zhang H, Sun S, Su S, Kong D, Wang Q. Revealment study on the regulation of lipid metabolism by Lingguizhugan Decoction in heart failure treatment based on integrated lipidomics and proteomics. Biomed Pharmacother 2023; 158:114066. [PMID: 36528915 DOI: 10.1016/j.biopha.2022.114066] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2022] [Revised: 11/29/2022] [Accepted: 12/02/2022] [Indexed: 12/23/2022] Open
Abstract
Lingguizhugan Decoction (LGZGD) is a classical traditional Chinese medicine prescription. Our previous studies found that disorders of lipid metabolism were reversed by LGZGD in heart failure (HF) mice. This study aimed to reveal the regulation of lipid metabolism of LGZGD. A mice model of HF was established by intraperitoneal injection of doxorubicin. The components of LGZGD were identified with the UHPLC-QTOF-MS method. The regulation of lipid metabolism by LGZGD was detected by serum lipidomics and heart tissue proteomics. Molecular docking was further performed to screen active components. A total of 78 compounds in LGZGD were identified. Results of lipidomics showed that 37 lipids illustrated a significant recovery trend to normal after the treatment of LGZGD. Results of proteomics demonstrated that 55 proteins were altered by the administration of LGZGD in HF mice. After enrichment analysis, the Prakg2/Ucp2/Plin1 axis on the Apelin pathway plays a vital role in HF treatment by LGZGD. Nine active components exhibited the outstanding ability of binding to the apelin receptor with MM-GBSA value lower than -60 Kcal/mol. In conclusion, all results combined together revealed that multi-component in the LGZGD had beneficial effects on the HF through ameliorating lipid disorders, which provides a novel insight into the cardioprotective effects of LGZGD and its clinical application.
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Affiliation(s)
- Xu Wang
- School of Pharmacy, Hebei Medical University, Shijiazhuang, PR China
| | - Yanhua Gao
- School of Pharmacy, Hebei Medical University, Shijiazhuang, PR China
| | - Jia Zhang
- School of Pharmacy, Hebei Medical University, Shijiazhuang, PR China
| | - Huaxing Zhang
- Core Facilities and Centers, Hebei Medical University, Shijiazhuang, PR China
| | - Shuo Sun
- School of Pharmacy, Hebei Medical University, Shijiazhuang, PR China
| | - Suwen Su
- The Key Laboratory of Pharmacology and Toxicology for New Drugs, Department of Pharmacology, Hebei Medical University, Shijiazhuang, PR China
| | - Dezhi Kong
- School of Chinese Integrative Medicine, Hebei Medical University, Shijiazhuang, PR China.
| | - Qiao Wang
- School of Pharmacy, Hebei Medical University, Shijiazhuang, PR China.
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Ni J, Zhang H, Wang X, Liu Z, Nie T, Li L, Su J, Zhu Y, Ma C, Huang Y, Mao J, Gao X, Fan G. Rg3 regulates myocardial pyruvate metabolism via P300-mediated dihydrolipoamide dehydrogenase 2-hydroxyisobutyrylation in TAC-induced cardiac hypertrophy. Cell Death Dis 2022; 13:1073. [PMID: 36572672 PMCID: PMC9792576 DOI: 10.1038/s41419-022-05516-y] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2022] [Revised: 12/07/2022] [Accepted: 12/12/2022] [Indexed: 12/27/2022]
Abstract
The failing heart is characterized by an increase in glucose uptake and glycolytic rates that is not accompanied by a concomitant increase in glucose oxidation. Lower coupling of glucose oxidation to glycolysis possibly owes to unchanged or reduced pyruvate oxidation in mitochondria. Therefore, increasing pyruvate oxidation may lead to new therapies for heart disease. Dihydrolipoamide dehydrogenase (DLD) is a component of the pyruvate dehydrogenase complex (PDH). DLD mutations or defects are closely associated with metabolic diseases. However, few studies explore the effects of DLD mutants or acylation status on PDH activity and pyruvate metabolism. P300 is protein 2-hydroxyisobutyryltransferases in cells, and P300-dependent lysine 2-hydroxyisobutyrylation of glycolytic enzymes affects glucose metabolism. However, there are no relevant reports on the effect of 2-hydroxyisobutyrylation on the energy metabolism of heart failure, and it is worth further in-depth study. In this study, we showed that 2-hydroxyisobutyrylation is an essential protein translational modification (PTM) that regulates the activity of pyruvate dehydrogenase complex (PDHc). In a mouse model of transverse aortic constriction (TAC)-induced cardiac hypertrophy, the 2-hydroxyisobutylation of DLD was significantly increased, related to the decrease in PDH activity. In addition, our data provide clear evidence that DLD is a direct substrate of P300. As one of the main active ingredients of ginseng, ginsenoside Rg3 (Rg3) can reduce the 2-hydroxyisobutylation levels of DLD and restore the PDH activity by inhibiting the acyltransferase activity of P300, thereby producing beneficial effects whenever the heart is injured. Therefore, this study suggests a novel strategy for reversing myocardial hypertrophy.
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Affiliation(s)
- Jingyu Ni
- grid.412635.70000 0004 1799 2712National Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, 300381 Tianjin, China ,grid.412635.70000 0004 1799 2712Tianjin Key Laboratory of Translational Research of TCM Prescription and Syndrome, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, 300381 Tianjin, China ,grid.412635.70000 0004 1799 2712Medical Experiment Center, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, 300381 Tianjin, China ,grid.410648.f0000 0001 1816 6218Haihe Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, 301617 Tianjin, China
| | - Hao Zhang
- grid.412635.70000 0004 1799 2712National Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, 300381 Tianjin, China ,grid.412635.70000 0004 1799 2712Tianjin Key Laboratory of Translational Research of TCM Prescription and Syndrome, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, 300381 Tianjin, China ,grid.412635.70000 0004 1799 2712Medical Experiment Center, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, 300381 Tianjin, China
| | - Xiaodan Wang
- grid.412635.70000 0004 1799 2712National Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, 300381 Tianjin, China ,grid.412635.70000 0004 1799 2712Tianjin Key Laboratory of Translational Research of TCM Prescription and Syndrome, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, 300381 Tianjin, China ,grid.412635.70000 0004 1799 2712Medical Experiment Center, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, 300381 Tianjin, China
| | - Zhihao Liu
- grid.410648.f0000 0001 1816 6218Haihe Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, 301617 Tianjin, China
| | - Tong Nie
- grid.410648.f0000 0001 1816 6218Haihe Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, 301617 Tianjin, China
| | - Lan Li
- grid.410648.f0000 0001 1816 6218Haihe Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, 301617 Tianjin, China
| | - Jing Su
- grid.410648.f0000 0001 1816 6218Haihe Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, 301617 Tianjin, China
| | - Yan Zhu
- grid.410648.f0000 0001 1816 6218Haihe Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, 301617 Tianjin, China
| | - Chuanrui Ma
- grid.412635.70000 0004 1799 2712National Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, 300381 Tianjin, China ,grid.412635.70000 0004 1799 2712Tianjin Key Laboratory of Translational Research of TCM Prescription and Syndrome, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, 300381 Tianjin, China ,grid.412635.70000 0004 1799 2712Medical Experiment Center, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, 300381 Tianjin, China
| | - Yuting Huang
- Key Laboratory of Prevention and Treatment of Cardiovascular and Cerebrovascular Diseases of Ministry of Education, First Affiliated Hospital of Gannan Medical University, Gannan Medical University, 341000 Ganzhou, China
| | - Jingyuan Mao
- grid.412635.70000 0004 1799 2712National Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, 300381 Tianjin, China ,grid.412635.70000 0004 1799 2712Tianjin Key Laboratory of Translational Research of TCM Prescription and Syndrome, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, 300381 Tianjin, China ,grid.412635.70000 0004 1799 2712Medical Experiment Center, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, 300381 Tianjin, China
| | - Xiumei Gao
- grid.410648.f0000 0001 1816 6218Haihe Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, 301617 Tianjin, China
| | - Guanwei Fan
- grid.412635.70000 0004 1799 2712National Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, 300381 Tianjin, China ,grid.412635.70000 0004 1799 2712Tianjin Key Laboratory of Translational Research of TCM Prescription and Syndrome, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, 300381 Tianjin, China ,grid.412635.70000 0004 1799 2712Medical Experiment Center, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, 300381 Tianjin, China ,grid.410648.f0000 0001 1816 6218Haihe Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, 301617 Tianjin, China
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Feng Y, Ma F, Wu E, Cheng Z, Wang Z, Yang L, Zhang J. Ginsenosides: Allies of gastrointestinal tumor immunotherapy. Front Pharmacol 2022; 13:922029. [PMID: 36386161 PMCID: PMC9659574 DOI: 10.3389/fphar.2022.922029] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/17/2022] [Accepted: 09/26/2022] [Indexed: 09/25/2023] Open
Abstract
In the past decade, immunotherapy has been the most promising treatment for gastrointestinal tumors. But the low response rate and drug resistance remain major concerns. It is therefore imperative to develop adjuvant therapies to increase the effectiveness of immunotherapy and prevent drug resistance. Ginseng has been used in Traditional Chinese medicine as a natural immune booster for thousands of years. The active components of ginseng, ginsenosides, have played an essential role in tumor treatment for decades and are candidates for anti-tumor adjuvant therapy. They are hypothesized to cooperate with immunotherapy drugs to improve the curative effect and reduce tumor resistance and adverse reactions. This review summarizes the research into the use of ginsenosides in immunotherapy of gastrointestinal tumors and discusses potential future applications.
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Affiliation(s)
| | | | | | | | | | | | - Jiwei Zhang
- Shanghai Key Laboratory of Compound Chinese Medicines, The MOE Key Laboratory for Standardization of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai, China
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The Molecular Mechanisms of Panax ginseng in Treating Type 2 Diabetes Mellitus: Network Pharmacology Analysis and Molecular Docking Validation. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2022; 2022:3082109. [PMID: 36159557 PMCID: PMC9507733 DOI: 10.1155/2022/3082109] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/04/2022] [Revised: 08/07/2022] [Accepted: 08/17/2022] [Indexed: 11/18/2022]
Abstract
Background Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder with a high global incidence. Panax ginseng has been used to treat T2DM in traditional medicine, with previous in vitro, in vivo, and clinical trial studies demonstrating its efficacy. This study aimed to determine the mechanism of P. ginseng in treating T2DM by network pharmacology. Methods The bioactive compounds of P. ginseng and corresponding targets of P. ginseng-T2DM were retrieved across multiple databases. The protein-protein interaction network was established using the STRING database and topological analysis helped identify the core target. Using the DAVID tool, we performed Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. Finally, we checked the binding of core targets and bioactive compounds using molecular docking. Results The P. ginseng-T2DM networks mainly contained 22 bioactive compounds and 314 overlapping targets. The five most significant core targets were SRC, STAT3, MAPK1, AKT1, and PIK3R1. There were 244 GO terms and 95 KEGG pathways (adjusted p < 0.01) that were strongly correlated with diabetes-related signaling pathways, such as insulin resistance, the HIF-1 signaling pathway, the PI3K/Akt signaling pathway, the prolactin signaling pathway, the Rap1 signaling pathway, the Ras signaling pathway, the calcium signaling pathway, and the FoxO signaling pathway. Molecular docking results revealed that the top five core targets had a high binding affinity with the bioactive compounds of P. ginseng. Conclusion The bioactive compounds and targets in P. ginseng ameliorate T2DM by regulating insulin resistance and multiple signaling pathways.
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Zhou W, Chen Z, Fang Z, Xu D. Network analysis for elucidating the mechanisms of Shenfu injection in preventing and treating COVID-19 combined with heart failure. Comput Biol Med 2022; 148:105845. [PMID: 35849948 PMCID: PMC9279168 DOI: 10.1016/j.compbiomed.2022.105845] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2021] [Revised: 05/08/2022] [Accepted: 05/09/2022] [Indexed: 11/23/2022]
Abstract
BACKGROUND The emergence of the novel coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to millions of infections and is exerting an unprecedented impact on society and economies worldwide. The evidence showed that heart failure (HF) is a clinical syndrome that could be encountered at different stages during the progression of COVID-19. Shenfu injection (SFI), a traditional Chinese medicine (TCM) formula has been widely used for heart failure therapy in China and was suggested to treat critical COVID-19 cases based on the guideline for diagnosis and treatment of COVID-19 (the 7th version) issued by National Health Commission of the People's Republic of China. However, the active components, potential targets, related pathways, and underlying pharmacology mechanism of SFI against COVID-19 combined with HF remain vague. OBJECTIVE To investigate the effectiveness and possible pharmacological mechanism of SFI for the prevention and treatment of COVID-19 combined with HF. METHODS In the current study, a network analysis approach integrating active compound screening (drug-likeness, lipophilicity, and aqueous solubility models), target fishing (Traditional Chinese Medicine Systems Pharmacology, fingerprint-based Similarity Ensemble Approach, and PharmMapper databases), compound-target-disease network construction (Cytoscape software), protein-protein interaction network construction (STRING and Cytoscape software), biological process analysis (STRING and Cytoscape plug-in Clue GO) and pathway analysis (Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis) was developed to decipher the active ingredients, potential targets, relevant pathways, and the therapeutic mechanisms of SFI for preventing and treating COVID-19 combined with HF. RESULTS Finally, 20 active compounds (DL ≥ 0.18, 1≤Alog P ≤ 5, and -5≤LogS ≤ -1) and 164 relevant targets of SFI were identified related to the development of COVID-19 combined with HF, which were mainly involved in three biological processes including metabolic, hemostasis, and cytokine signaling in immune system. The C-T-D network and reactome pathway analysis indicated that SFI probably regulated the pathological processes of heart failure, respiratory failure, lung injury, and inflammatory response in patients with COVID-19 combined with HF through acting on several targets and pathways. Moreover, the venn diagram was used to identify 54 overlapped targets of SFI, COVID-19, and HF. KEGG pathway enrichment analysis showed that 54 overlapped targets were highly enriched to several COVID-19 and HF related pathways, such as IL-17 signaling pathway, Th17 cell differentiation, and NF-kappa B signaling pathway. CONCLUSIONS A comprehensive network analysis approach framework was developed to systematically elucidate the potential pharmacological mechanism of SFI for the prevention and treatment of SFI against COVID-19 combined with HF. The current study may not only provide in-depth understanding of the pharmacological mechanisms of SFI, but also a scientific basis for the application of SFI against COVID-19 combined with HF.
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Affiliation(s)
- Wei Zhou
- State Key Laboratory of Respiratory Disease for Allergy at Shenzhen University, Shenzhen Key Laboratory of Allergy & Immunology, Shenzhen University School of Medicine, Shenzhen University, Shenzhen, 518020, China; Department of Respirology & Allergy. Third Affiliated Hospital of Shenzhen University. Shenzhen University, Shenzhen, 518020, China.
| | - Ziyi Chen
- Musculoskeletal Research Laboratory, Department of Orthopaedics & Traumatology, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, 999077, Hong Kong, China
| | - Zhangfu Fang
- Department of Respirology & Allergy. Third Affiliated Hospital of Shenzhen University. Shenzhen University, Shenzhen, 518020, China
| | - Damo Xu
- State Key Laboratory of Respiratory Disease for Allergy at Shenzhen University, Shenzhen Key Laboratory of Allergy & Immunology, Shenzhen University School of Medicine, Shenzhen University, Shenzhen, 518020, China; Department of Respirology & Allergy. Third Affiliated Hospital of Shenzhen University. Shenzhen University, Shenzhen, 518020, China
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