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Xiao P, Ye Z, Li X, Feng Q, Su Y. Ginseng and its functional components in non-alcoholic fatty liver disease: therapeutic effects and multi-target pharmacological mechanisms. Front Pharmacol 2025; 16:1540255. [PMID: 40271056 PMCID: PMC12014752 DOI: 10.3389/fphar.2025.1540255] [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: 12/05/2024] [Accepted: 03/28/2025] [Indexed: 04/25/2025] Open
Abstract
Background Non-alcoholic fatty liver disease (NAFLD) is a common type of chronic liver disease and its incidence is increasing. Its disease progression is closely related to non-alcoholic steatohepatitis and liver fibrosis. Effective treatment is currently lacking. The traditional Chinese medicine ginseng (Panax ginseng) shows unique advantages in NAFLD intervention, but its complex compositional system and molecular mechanism network still need to be systematically analyzed. Objective This paper systematically integrates evidence from nearly 20 years of research to elucidate the multi-target pharmacological mechanism of ginseng for the treatment of NAFLD. Methods Relevant information was sourced from Pubmed, Web of science, Embase and CNKI databases. Using BioRender and visio to draw biomedical illustrations. Results The active ingredients of ginseng contain 2 classes of saponins (tetracyclic triterpene saponins, pentacyclic triterpene saponins and other modified types) and non-saponins. Different cultivation methods, processing techniques and extraction sites have expanded the variety of ginseng constituents and demonstrated different pharmacological activities. Studies have shown that ginseng and its functional components have the ability to regulate lipid metabolism disorders, inflammation, oxidative stress, endoplasmic reticulum stress, insulin resistance, disruption of intestinal flora structure, cell death and senescence. Demonstrates the potential of ginseng for the treatment of NAFLD. Conclusion This study reveals for the first time the integrative mechanism of ginseng in the treatment of NAFLD through the tertiary mode of action of "multi-component multi-target multi-pathway". The multilevel modulatory ability of ginseng provides a new direction for the development of comprehensive therapeutic strategies for NAFLD.
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Affiliation(s)
| | | | | | - Quansheng Feng
- School of Basic Medical Sciences, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Yue Su
- School of Basic Medical Sciences, Chengdu University of Traditional Chinese Medicine, Chengdu, China
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Hao L, Li S, Li C, Zhang Z, Hu X, Yan H. A Review of the Therapeutic Potential of Ginseng and Its Bioactive Components in Nonalcoholic Fatty Liver Disease. Drug Des Devel Ther 2025; 19:83-96. [PMID: 39803604 PMCID: PMC11725245 DOI: 10.2147/dddt.s500719] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2024] [Accepted: 12/10/2024] [Indexed: 01/16/2025] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) is the major cause of chronic liver disease worldwide, with no universally recognized effective treatments currently available. In recent years, ginseng and its principal active components, such as ginsenosides, have shown potential protective effects in the treatment of these liver diseases. In NAFLD, studies have demonstrated that ginseng can improve hepatic lipid metabolism, reduce inflammatory responses, and inhibit oxidative stress and fibrosis, thereby attenuating the progression of NAFLD. Additionally, ginseng inhibits oxidative stress by scavenging free radicals and enhancing antioxidant enzyme activities, and it can impede fibrosis by interfering with the fibrotic signaling pathways. These combined effects contribute to attenuating the progression of NAFLD. These findings highlight the promise of ginseng as a potential therapeutic candidate for the treatment of NAFLD. However, despite the significant efficacy of ginseng in human NAFLD treatment, the number and quality of clinical studies remain limited, with a lack of large-scale, multicenter clinical trials to confirm these effects. Moreover, the pharmacokinetic properties of different ginsenosides, optimal therapeutic dosages, and the safety of long-term use require further investigation. This review summarizes the existing evidence on the mechanisms of action of ginseng and its active components in human NAFLD, assesses their potential as therapeutic options, and proposes future research directions to provide stronger scientific support for clinical application. Additionally, we performed a network pharmacology analysis of ginseng in relation to NAFLD to identify and investigate potential targets of ginseng in the treatment of NAFLD. This analysis aims to provide a theoretical foundation for the development of ginseng -based drugs for combating NAFLD.
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Affiliation(s)
- Liyuan Hao
- School of Clinical Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, People’s Republic of China
- Department of Infectious Diseases, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, People’s Republic of China
| | - Shenghao Li
- School of Clinical Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, People’s Republic of China
- Department of Infectious Diseases, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, People’s Republic of China
- Clinical Research Center, Shijiazhuang Fifth Hospital, Shijiazhuang, Hebei, People’s Republic of China
| | - Caige Li
- Department of Endocrinology, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, People’s Republic of China
| | - Zhiqin Zhang
- College of Integrated Traditional Chinese and Western Medicine, Hebei University of Traditional Chinese Medicine, Shijiazhuang, Hebei, People’s Republic of China
| | - Xiaoyu Hu
- Department of Infectious Diseases, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, People’s Republic of China
| | - Huimin Yan
- Clinical Research Center, Shijiazhuang Fifth Hospital, Shijiazhuang, Hebei, People’s Republic of China
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Wang D, Zhang J, Yin H, Yan R, Wang Z, Deng J, Li G, Pan Y. The anti-tumor effects of cosmosiin through regulating AhR/CYP1A1-PPARγ in breast cancer. FASEB J 2024; 38:e70002. [PMID: 39162680 DOI: 10.1096/fj.202401191r] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/28/2024] [Revised: 07/21/2024] [Accepted: 08/07/2024] [Indexed: 08/21/2024]
Abstract
Breast cancer is one of the threatening malignant tumors with the highest mortality and incidence rate over the world. There are a lot of breast cancer patients dying every year due to the lack of effective and safe therapeutic drugs. Therefore, it is highly necessary to develop more effective drugs to overcome breast cancer. As a glycoside derivative of apigenin, cosmosiin is characterized by low toxicity, high water solubility, and wide distribution in nature. Additionally, cosmosiin has been shown to perform anti-tumor effects in cervical cancer, hepatocellular carcinoma and melanoma. However, its pharmacological effects on breast cancer and its mechanisms are still unknown. In our study, the anti-breast cancer effect and mechanism of cosmosiin were investigated by using breast cancer models in vivo and in vitro. The results showed that cosmosiin inhibited the proliferation, migration, and adhesion of breast cancer cells in vitro and suppressed the growth of tumor in vivo through binding with AhR and inhibiting it, thus regulating the downstream CYP1A1/AMPK/mTOR and PPARγ/Wnt/β-catenin signaling pathways. Collectively, our findings have made contribution to the development of novel drugs against breast cancer by targeting AhR and provided a new direction for the research in the field of anti-breast cancer therapy.
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Affiliation(s)
- Dan Wang
- Department of Pharmacology, School of Basic Medical Sciences, Health Science Center, Peking University, Beijing, China
| | - Jing Zhang
- Inner Mongolia Key Laboratory of Molecular Biology, Inner Mongolia Medical University, Hohhot, China
| | - Houqing Yin
- Department of Pharmacology, School of Basic Medical Sciences, Health Science Center, Peking University, Beijing, China
| | - Ribai Yan
- School of Pharmaceutical Sciences, Peking University, Beijing, China
| | - Zequn Wang
- Department of Pharmacology, School of Basic Medical Sciences, Health Science Center, Peking University, Beijing, China
| | - Jinhai Deng
- Richard Dimbleby Laboratory of Cancer Research, School of Cancer & Pharmaceutical Sciences, King's College London, London, UK
| | - Gang Li
- Department of General Surgery, Peking University Third Hospital, Beijing, China
| | - Yan Pan
- Department of Pharmacology, School of Basic Medical Sciences, Health Science Center, Peking University, Beijing, China
- Beijing Key Laboratory of Tumor Systems Biology, Peking University, Beijing, China
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Merenda T, Juszczak F, Ferier E, Duez P, Patris S, Declèves AÉ, Nachtergael A. Natural compounds proposed for the management of non-alcoholic fatty liver disease. NATURAL PRODUCTS AND BIOPROSPECTING 2024; 14:24. [PMID: 38556609 PMCID: PMC10982245 DOI: 10.1007/s13659-024-00445-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/16/2024] [Accepted: 03/20/2024] [Indexed: 04/02/2024]
Abstract
Although non-alcoholic fatty liver disease (NAFLD) presents as an intricate condition characterized by a growing prevalence, the often-recommended lifestyle interventions mostly lack high-level evidence of efficacy and there are currently no effective drugs proposed for this indication. The present review delves into NAFLD pathology, its diverse underlying physiopathological mechanisms and the available in vitro, in vivo, and clinical evidence regarding the use of natural compounds for its management, through three pivotal targets (oxidative stress, cellular inflammation, and insulin resistance). The promising perspectives that natural compounds offer for NAFLD management underscore the need for additional clinical and lifestyle intervention trials. Encouraging further research will contribute to establishing more robust evidence and practical recommendations tailored to patients with varying NAFLD grades.
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Affiliation(s)
- Théodora Merenda
- Unit of Clinical Pharmacy, Research Institute for Health Sciences and Technology, University of Mons (UMONS), Mons, Belgium
| | - Florian Juszczak
- Department of Metabolic and Molecular Biochemistry, Research Institute for Health Sciences and Technology, University of Mons (UMONS), Mons, Belgium
| | - Elisabeth Ferier
- Department of Metabolic and Molecular Biochemistry, Research Institute for Health Sciences and Technology, University of Mons (UMONS), Mons, Belgium
- Unit of Therapeutic Chemistry and Pharmacognosy, Research Institute for Health Sciences and Technology, University of Mons (UMONS), Mons, Belgium
| | - Pierre Duez
- Unit of Therapeutic Chemistry and Pharmacognosy, Research Institute for Health Sciences and Technology, University of Mons (UMONS), Mons, Belgium
| | - Stéphanie Patris
- Unit of Clinical Pharmacy, Research Institute for Health Sciences and Technology, University of Mons (UMONS), Mons, Belgium
| | - Anne-Émilie Declèves
- Department of Metabolic and Molecular Biochemistry, Research Institute for Health Sciences and Technology, University of Mons (UMONS), Mons, Belgium
| | - Amandine Nachtergael
- Unit of Therapeutic Chemistry and Pharmacognosy, Research Institute for Health Sciences and Technology, University of Mons (UMONS), Mons, Belgium.
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Morshed MN, Akter R, Karim MR, Iqbal S, Kang SC, Yang DC. Bioconversion, Pharmacokinetics, and Therapeutic Mechanisms of Ginsenoside Compound K and Its Analogues for Treating Metabolic Diseases. Curr Issues Mol Biol 2024; 46:2320-2342. [PMID: 38534764 DOI: 10.3390/cimb46030148] [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: 02/14/2024] [Revised: 03/01/2024] [Accepted: 03/06/2024] [Indexed: 03/28/2024] Open
Abstract
Rare ginsenoside compound K (CK) is an intestinal microbial metabolite with a low natural abundance that is primarily produced by physicochemical processing, side chain modification, or metabolic transformation in the gut. Moreover, CK exhibits potent biological activity compared to primary ginsenosides, which has raised concerns in the field of ginseng research and development, as well as ginsenoside-related dietary supplements and natural products. Ginsenosides Rb1, Rb2, and Rc are generally used as a substrate to generate CK via several bioconversion processes. Current research shows that CK has a wide range of pharmacological actions, including boosting osteogenesis, lipid and glucose metabolism, lipid oxidation, insulin resistance, and anti-inflammatory and anti-apoptosis properties. Further research on the bioavailability and toxicology of CK can advance its medicinal application. The purpose of this review is to lay the groundwork for future clinical studies and the development of CK as a therapy for metabolic disorders. Furthermore, the toxicology and pharmacology of CK are investigated as well in this review. The findings indicate that CK primarily modulates signaling pathways associated with AMPK, SIRT1, PPARs, WNTs, and NF-kB. It also demonstrates a positive therapeutic effect of CK on non-alcoholic fatty liver disease (NAFLD), obesity, hyperlipidemia, diabetes, and its complications, as well as osteoporosis. Additionally, the analogues of CK showed more bioavailability, less toxicity, and more efficacy against disease states. Enhancing bioavailability and regulating hazardous variables are crucial for its use in clinical trials.
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Affiliation(s)
- Md Niaj Morshed
- Department of Biopharmaceutical Biotechnology, College of Life Science, Kyung Hee University, Yongin-si 17104, Republic of Korea
| | - Reshmi Akter
- Graduate School of Biotechnology, College of Life Sciences, Kyung Hee University, Yongin-si 17104, Republic of Korea
| | - Md Rezaul Karim
- Department of Biopharmaceutical Biotechnology, College of Life Science, Kyung Hee University, Yongin-si 17104, Republic of Korea
| | - Safia Iqbal
- Department of Biopharmaceutical Biotechnology, College of Life Science, Kyung Hee University, Yongin-si 17104, Republic of Korea
| | - Se Chan Kang
- Department of Biopharmaceutical Biotechnology, College of Life Science, Kyung Hee University, Yongin-si 17104, Republic of Korea
| | - Deok Chun Yang
- Graduate School of Biotechnology, College of Life Sciences, Kyung Hee University, Yongin-si 17104, Republic of Korea
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Song Z, Jin M, Wang S, Wu Y, Huang Q, Xu W, Fan Y, Tian F. Reciprocal regulation of SIRT1 and AMPK by Ginsenoside compound K impedes the conversion from plasma cells to mitigate for podocyte injury in MRL/ lpr mice in a B cell-specific manner. J Ginseng Res 2024; 48:190-201. [PMID: 38465215 PMCID: PMC10920007 DOI: 10.1016/j.jgr.2023.11.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2023] [Revised: 11/27/2023] [Accepted: 11/28/2023] [Indexed: 03/12/2024] Open
Abstract
Background Deposition of immune complexes drives podocyte injury acting in the initial phase of lupus nephritis (LN), a process mediated by B cell involvement. Accordingly, targeting B cell subsets represents a potential therapeutic approach for LN. Ginsenoside compound K (CK), a bioavailable component of ginseng, possesses nephritis benefits in lupus-prone mice; however, the underlying mechanisms involving B cell subpopulations remain elusive. Methods Female MRL/lpr mice were administered CK (40 mg/kg) intragastrically for 10 weeks, followed by measurements of anti-dsDNA antibodies, inflammatory chemokines, and metabolite profiles on renal samples. Podocyte function and ultrastructure were detected. Publicly available single-cell RNA sequencing data and flow cytometry analysis were employed to investigate B cell subpopulations. Metabolomics analysis was adopted. SIRT1 and AMPK expression were analyzed by immunoblotting and immunofluorescence assays. Results CK reduced proteinuria and protected podocyte ultrastructure in MRL/lpr mice by suppressing circulating anti-dsDNA antibodies and mitigating systemic inflammation. It activated B cell-specific SIRT1 and AMPK with Rhamnose accumulation, hindering the conversion of renal B cells into plasma cells. This cascade facilitated the resolution of local renal inflammation. CK facilitated the clearance of deposited immune complexes, thus reinstating podocyte morphology and mobility by normalizing the expression of nephrin and SYNPO. Conclusions Our study reveals the synergistic interplay between SIRT1 and AMPK, orchestrating the restoration of renal B cell subsets. This process effectively mitigates immune complex deposition and preserves podocyte function. Accordingly, CK emerges as a promising therapeutic agent, potentially alleviating the hyperactivity of renal B cell subsets during LN.
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Affiliation(s)
- Ziyu Song
- First School of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, China
| | - Meng Jin
- First School of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, China
| | - Shenglong Wang
- First School of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, China
| | - Yanzuo Wu
- First School of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, China
| | - Qi Huang
- Department of Endocrinology, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, China
| | - Wangda Xu
- First School of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, China
| | - Yongsheng Fan
- College of Basic Medical Science, Institute of Basic Research in Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, China
| | - Fengyuan Tian
- First School of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, China
- General Practice, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, China
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Yi YS. Pharmacological potential of ginseng and ginsenosides in nonalcoholic fatty liver disease and nonalcoholic steatohepatitis. J Ginseng Res 2024; 48:122-128. [PMID: 38465218 PMCID: PMC10920004 DOI: 10.1016/j.jgr.2023.11.003] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2023] [Revised: 10/01/2023] [Accepted: 11/10/2023] [Indexed: 03/12/2024] Open
Abstract
Nonalcoholic fatty liver disease (NAFLD) is a chronic liver disease characterized by hepatic fat accumulation, while nonalcoholic steatohepatitis (NASH) is an advanced form of NAFLD characterized by hepatic inflammation, fibrosis, and liver injury, resulting in liver cirrhosis and hepatocellular carcinoma (HCC). Given the evidence that ginseng and its major bioactive components, ginsenosides, have potent anti-adipogenic, anti-inflammatory, anti-oxidative, and anti-fibrogenic effects, the pharmacological effect of ginseng and ginsenosides on NAFLD and NASH is noteworthy. Furthermore, numerous studies have successfully demonstrated the protective effect of ginseng on these diseases, as well as the underlying mechanisms in animal disease models and cells, such as hepatocytes and macrophages. This review discusses recent studies that explore the pharmacological roles of ginseng and ginsenosides in NAFLD and NASH and highlights their potential as agents to prevent and treat NAFLD, NASH, and liver diseases caused by hepatic steatosis and inflammation.
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Affiliation(s)
- Young-Su Yi
- Department of Life Sciences, Kyonggi University, 154-42 Gwanggyosan-ro, Yeongtong-gu, Suwon, Republic of Korea
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Du T, Xiang L, Zhang J, Yang C, Zhao W, Li J, Zhou Y, Ma L. Vitamin D improves hepatic steatosis in NAFLD via regulation of fatty acid uptake and β-oxidation. Front Endocrinol (Lausanne) 2023; 14:1138078. [PMID: 37033263 PMCID: PMC10074590 DOI: 10.3389/fendo.2023.1138078] [Citation(s) in RCA: 16] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/05/2023] [Accepted: 03/02/2023] [Indexed: 04/11/2023] Open
Abstract
INTRODUCTION The study aimed to explore the association of serum 25(OH)D3 and hepatic steatosis in non-alcoholic fatty liver disease (NAFLD) patients and to determine whether the effect of vitamin D (VD) is mediated by activation of the peroxisome proliferator-activated receptor α (PPARα) pathway. METHODS The study contained a case-control study, in vivo and in vitro experiments. A case-control study was conducted to compare serum parameters between NAFLD patients and controls and to evaluate the association of 25(OH)D3 and NAFLD. In vivo study, male Wistar rats were randomly divided into control and model groups, fed a standard chow diet and a high-fat diet (HFD), respectively, for 7 weeks to generate an NAFLD model. Then, the rats were treated with VD and a PPARα antagonist (MK886) for 7 weeks. Tissue and serum were collected and assessed by biochemical assays, morphological analysis, histological analysis, and western blot analysis. In vitro, HepG2 cells were incubated with oleic acid (OA) to induce steatosis, which was evaluated by staining. HepG2 cells were pretreated with MK886 followed by calcitriol treatment, and differences in lipid metabolism-related proteins were detected by western blot. RESULTS NAFLD patients were characterized by impaired liver function, dyslipidemia, and insulin resistance. Serum 25(OH)D3 was negatively associated with alanine aminotransferase (ALT) in NAFLD. VD deficiency was a risk factor for patients with no advanced fibrosis. Adequate VD status (25(OH)D3 >20 ng/mL) had a protective effect in patients after adjustment for confounding variables. NAFLD rats showed hyperlipidemia with severe hepatic steatosis, systematic inflammation, and lower serum 25(OH)D3. VD treatment ameliorated hepatic steatosis both in NAFLD rats and OA-induced HepG2 cells. Further, MK886 inhibited the anti-steatosis effect of VD. CONCLUSION The study revealed that an adequate VD level may act as a protective factor in NAFLD and that VD may alleviate hepatic steatosis via the PPARα signaling pathway.
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Affiliation(s)
- Tingwan Du
- Department of Nutrition and Food Hygiene, School of Public Health, Southwest Medical University, Luzhou, China
| | - Lian Xiang
- Department of Nutrition and Food Hygiene, School of Public Health, Southwest Medical University, Luzhou, China
| | - Jingjing Zhang
- Department of Clinical Nutrition, The Affiliated Hospital of Southwest Medical University, Luzhou, China
| | - Chunmei Yang
- Health Management Center, The Affiliated Hospital of Southwest Medical University, Luzhou, China
| | - Wenxin Zhao
- Department of Nutrition and Food Hygiene, School of Public Health, Southwest Medical University, Luzhou, China
| | - Jialu Li
- Department of Nutrition and Food Hygiene, School of Public Health, Southwest Medical University, Luzhou, China
| | - Yong Zhou
- Department of Medical Cell Biology and Genetics, School of Basic Medical Science, Southwest Medical University, Luzhou, China
- *Correspondence: Yong Zhou, ; Ling Ma,
| | - Ling Ma
- Department of Nutrition and Food Hygiene, School of Public Health, Southwest Medical University, Luzhou, China
- Environmental Health Effects and Risk Assessment Key Laboratory of Luzhou, School of Public Health, Southwest Medical University, Luzhou, China
- *Correspondence: Yong Zhou, ; Ling Ma,
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Yang L, Zheng L, Xie X, Luo J, Yu J, Zhang L, Meng W, Zhou Y, Chen L, Ouyang D, Zhou H, Tan Z. Targeting PLA2G16, a lipid metabolism gene, by Ginsenoside Compound K to suppress the malignant progression of colorectal cancer. J Adv Res 2022; 36:265-276. [PMID: 35127176 PMCID: PMC8799872 DOI: 10.1016/j.jare.2021.06.009] [Citation(s) in RCA: 20] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2021] [Revised: 04/16/2021] [Accepted: 06/09/2021] [Indexed: 02/07/2023] Open
Abstract
PLA2G16 is up-regulated in CRC, and high expression of PLA2G16 is associated with the advanced stages. PLA2G16 promotes the malignant progression of CRC through the Hippo signaling pathway. GCK exerts its anti-CRC effects by inhibiting the protein expression of PLA2G16. Provide a new insights towards the development of effective therapeutic strategies for CRC treatment by targeting PLA2G16. Introduction Objectives Methods Results Conclusion
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Ginsenosides for the treatment of metabolic syndrome and cardiovascular diseases: Pharmacology and mechanisms. Biomed Pharmacother 2020; 132:110915. [DOI: 10.1016/j.biopha.2020.110915] [Citation(s) in RCA: 41] [Impact Index Per Article: 8.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2020] [Revised: 10/05/2020] [Accepted: 10/17/2020] [Indexed: 12/16/2022] Open
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Therapeutic potential of ginsenosides on diabetes: From hypoglycemic mechanism to clinical trials. J Funct Foods 2020. [DOI: 10.1016/j.jff.2019.103630] [Citation(s) in RCA: 21] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
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Zhou L, Chen L, Zeng X, Liao J, Ouyang D. Ginsenoside compound K alleviates sodium valproate-induced hepatotoxicity in rats via antioxidant effect, regulation of peroxisome pathway and iron homeostasis. Toxicol Appl Pharmacol 2019; 386:114829. [PMID: 31734319 DOI: 10.1016/j.taap.2019.114829] [Citation(s) in RCA: 26] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2019] [Revised: 11/13/2019] [Accepted: 11/13/2019] [Indexed: 02/07/2023]
Abstract
Sodium valproate (SVP) is a first-line treatment for various forms of epilepsy; however, it can cause severe liver injury. Ginsenoside compound K (G-CK) is the main active ingredient of the traditional herbal medicine ginseng. According to our previous research, SVP-induced elevation of ALT and AST levels, as well as pathological changes of liver tissue, was believed to be significantly reversed by G-CK in LiCl-pilocarpine induced epileptic rats. Thus, we aimed to evaluate the protective effect of G-CK on hepatotoxicity caused by SVP. The rats treated with SVP showed liver injury with evident increases in hepatic index, transaminases activity, alkaline phosphatase level, hepatic triglyceride and lipid peroxidation; significant decreases in plasma albumin level and antioxidant capacity; and obvious changes in histopathological and subcellular structures. All of these changes could be mitigated by co-administration with G-CK. Proteomic analysis indicated that hepcidin, soluble epoxide hydrolase (sEH, UniProt ID P80299), and the peroxisome pathway were involved in the hepatoprotective effect of G-CK. Changes in protein expression of hepcidin and sEH were verified by ELISA and Western blot analysis, respectively. In addition, we observed that the hepatic iron rose in SVP group and decreased in the combination group. In summary, our findings demonstrate the clear hepatoprotective effect of G-CK against SVP-induced hepatotoxicity through the antioxidant effect, regulation of peroxisome pathway relying on sEH (P80299) downregulation, as well as regulation of iron homeostasis dependent on hepcidin upregulation.
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Affiliation(s)
- Luping Zhou
- Department of Clinical Pharmacology, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha 410008, P.R. China; Institute of Clinical Pharmacology, Central South University, Hunan Key Laboratory of Pharmacogenetics, 110 Xiangya Road, Changsha 410078, P.R. China; Engineering Research Center of Applied Technology of Pharmacogenomics, Ministry of Education, 110 Xiangya Road, Changsha 410078, P.R. China; National Clinical Research Center for Geriatric Disorders, 87 Xiangya Road, Changsha 410008, Hunan, P.R. China
| | - Lulu Chen
- Department of Clinical Pharmacology, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha 410008, P.R. China; Institute of Clinical Pharmacology, Central South University, Hunan Key Laboratory of Pharmacogenetics, 110 Xiangya Road, Changsha 410078, P.R. China; Engineering Research Center of Applied Technology of Pharmacogenomics, Ministry of Education, 110 Xiangya Road, Changsha 410078, P.R. China; National Clinical Research Center for Geriatric Disorders, 87 Xiangya Road, Changsha 410008, Hunan, P.R. China; Hunan Key Laboratory for Bioanalysis of Complex Matrix Samples, Changsha, Hunan 410000, P.R. China
| | - Xiangchang Zeng
- Department of Clinical Pharmacology, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha 410008, P.R. China; Institute of Clinical Pharmacology, Central South University, Hunan Key Laboratory of Pharmacogenetics, 110 Xiangya Road, Changsha 410078, P.R. China; Engineering Research Center of Applied Technology of Pharmacogenomics, Ministry of Education, 110 Xiangya Road, Changsha 410078, P.R. China; National Clinical Research Center for Geriatric Disorders, 87 Xiangya Road, Changsha 410008, Hunan, P.R. China
| | - Jianwei Liao
- Department of Clinical Pharmacology, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha 410008, P.R. China; Institute of Clinical Pharmacology, Central South University, Hunan Key Laboratory of Pharmacogenetics, 110 Xiangya Road, Changsha 410078, P.R. China; Engineering Research Center of Applied Technology of Pharmacogenomics, Ministry of Education, 110 Xiangya Road, Changsha 410078, P.R. China; National Clinical Research Center for Geriatric Disorders, 87 Xiangya Road, Changsha 410008, Hunan, P.R. China
| | - Dongsheng Ouyang
- Department of Clinical Pharmacology, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha 410008, P.R. China; Institute of Clinical Pharmacology, Central South University, Hunan Key Laboratory of Pharmacogenetics, 110 Xiangya Road, Changsha 410078, P.R. China; Engineering Research Center of Applied Technology of Pharmacogenomics, Ministry of Education, 110 Xiangya Road, Changsha 410078, P.R. China; National Clinical Research Center for Geriatric Disorders, 87 Xiangya Road, Changsha 410008, Hunan, P.R. China; Hunan Key Laboratory for Bioanalysis of Complex Matrix Samples, Changsha, Hunan 410000, P.R. China.
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Cui CH, Jeon BM, Fu Y, Im WT, Kim SC. High-density immobilization of a ginsenoside-transforming β-glucosidase for enhanced food-grade production of minor ginsenosides. Appl Microbiol Biotechnol 2019; 103:7003-7015. [PMID: 31289903 PMCID: PMC6690934 DOI: 10.1007/s00253-019-09951-4] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2019] [Revised: 05/26/2019] [Accepted: 05/28/2019] [Indexed: 02/06/2023]
Abstract
Use of recombinant glycosidases is a promising approach for the production of minor ginsenosides, e.g., Compound K (CK) and F1, which have potential applications in the food industry. However, application of these recombinant enzymes for food-grade preparation of minor ginsenosides are limited by the lack of suitable expression hosts and low productivity. In this study, Corynebacterium glutamicum ATCC13032, a GRAS strain that has been used extensively for the industrial-grade production of additives for foodstuffs, was employed to express a novel β-glucosidase (MT619) from Microbacterium testaceum ATCC 15829 with high ginsenoside-transforming activity. A cellulose-binding module was additionally fused to the N-terminus of MT619 for immobilization on cellulose, which is an abundant and safe material. Via one-step immobilization, the fusion protein in cell lysates was efficiently immobilized on regenerated amorphous cellulose at a high density (maximum 984 mg/g cellulose), increasing the enzyme concentration by 286-fold. The concentrated and immobilized enzyme showed strong conversion activities against protopanaxadiol- and protopanaxatriol-type ginsenosides for the production of CK and F1. Using gram-scale ginseng extracts as substrates, the immobilized enzyme produced 7.59 g/L CK and 9.42 g/L F1 in 24 h. To the best of our knowledge, these are the highest reported product concentrations of CK and F1, and this is the first time that a recombinant enzyme has been immobilized on cellulose for the preparation of minor ginsenosides. This safe, convenient, and efficient production method could also be effectively exploited in the preparation of food-processing recombinant enzymes in the pharmaceutical, functional food, and cosmetics industries.
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Affiliation(s)
- Chang-Hao Cui
- Intelligent Synthetic Biology Center, 291 Daehak-Ro, Yuseong-Gu, Daejeon, 305-701, Korea.,The Key Laboratory of Biotechnology for Medicinal Plant of Jiangsu Province, Jiangsu Normal University, No. 101 Shanghai Road, Xuzhou, Jiangsu, 221116, People's Republic of China
| | - Byeong-Min Jeon
- Department of Biological Sciences, Korea Advanced Institute of Science and Technology, 291 Daehak-Ro, Yuseong-Gu, Daejeon, 305-701, Korea
| | - Yaoyao Fu
- The Key Laboratory of Biotechnology for Medicinal Plant of Jiangsu Province, Jiangsu Normal University, No. 101 Shanghai Road, Xuzhou, Jiangsu, 221116, People's Republic of China
| | - Wan-Taek Im
- Department of Biological Sciences, Hankyong National University, 327 Chungang-Ro, Anseong City, Kyonggi-Do, 456-749, Korea
| | - Sun-Chang Kim
- Intelligent Synthetic Biology Center, 291 Daehak-Ro, Yuseong-Gu, Daejeon, 305-701, Korea. .,Department of Biological Sciences, Korea Advanced Institute of Science and Technology, 291 Daehak-Ro, Yuseong-Gu, Daejeon, 305-701, Korea. .,KAIST Institute for Biocentury, Korea Advanced Institute of Science and Technology, 291 Daehak-Ro, Yuseong-Gu, Daejeon, 305-701, Korea.
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14
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Han JS, Sung JH, Lee SK. Inhibition of Cholesterol Synthesis in HepG2 Cells by GINST-Decreasing HMG-CoA Reductase Expression Via AMP-Activated Protein Kinase. J Food Sci 2017; 82:2700-2705. [DOI: 10.1111/1750-3841.13828] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2016] [Revised: 06/16/2017] [Accepted: 06/30/2017] [Indexed: 12/27/2022]
Affiliation(s)
- Joon-Seung Han
- BioTech Research Laboratory; Central Research Inst.; Ilhwa Co., Ltd. Gangdong-gu Seoul 05288 Republic of Korea
| | - Jong Hwan Sung
- BioTech Research Laboratory; Central Research Inst.; Ilhwa Co., Ltd. Gangdong-gu Seoul 05288 Republic of Korea
| | - Seung Kwon Lee
- BioTech Research Laboratory; Central Research Inst.; Ilhwa Co., Ltd. Gangdong-gu Seoul 05288 Republic of Korea
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15
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Choi N, Kim JW, Jeong H, Shin DG, Seo JH, Kim JH, Lim CW, Han KM, Kim B. Fermented ginseng, GBCK25, ameliorates steatosis and inflammation in nonalcoholic steatohepatitis model. J Ginseng Res 2017; 43:196-208. [PMID: 30962734 PMCID: PMC6437395 DOI: 10.1016/j.jgr.2017.10.002] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2017] [Revised: 09/27/2017] [Accepted: 10/13/2017] [Indexed: 12/11/2022] Open
Abstract
Background Nonalcoholic steatohepatitis (NASH) is one of the chronic inflammatory liver diseases and a leading cause of advanced liver fibrosis, cirrhosis, and hepatocellular carcinoma. The main purpose of this study was to clarify the effects of GBCK25 fermented by Saccharomyces servazzii GB-07 and pectinase, on NASH severity in mice. Methods Six-wk-old male mice were fed either a normal diet (ND) or a Western diet (WD) for 12 wks to induce NASH. Each group was orally administered with vehicle or GBCK25 once daily at a dose of 10 mg/kg, 20 mg/kg, 100 mg/kg, 200 mg/kg, or 400 mg/kg during that time. The effects of GBCK25 on cellular damage and inflammation were determined by in vitro experiments. Results Histopathologic analysis and hepatic/serum biochemical levels revealed that WD-fed mice showed severe steatosis and liver injury compared to ND-fed mice. Such lesions were significantly decreased in the livers of WD-fed mice with GBCK25 administration. Consistently, mRNA expression levels of NASH-related inflammatory-, fibrogenic-, and lipid metabolism-related genes were decreased in the livers of WD-fed mice administered with GBCK25 compared to WD-fed mice. Western blot analysis revealed decreased protein levels of cytochrome P450 2E1 (CYP2E1) with concomitantly reduced activation of c-Jun N-terminal kinase (JNK) in the livers of WD-fed mice administered with GBCK25. Also, decreased cellular damage and inflammation were observed in alpha mouse liver 12 (AML12) cells and RAW264.7 cells, respectively. Conclusion Administration of GBCK25 ameliorates NASH severity through the modulation of CYP2E1 and its associated JNK-mediated cellular damage. GBCK25 could be a potentially effective prophylactic strategy to prevent metabolic diseases including NASH.
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Affiliation(s)
- Naeun Choi
- Biosafety Research Institute and Laboratory of Pathology (BK21 Plus Program), College of Veterinary Medicine, Chonbuk National University, Iksan, Republic of Korea
| | - Jong Won Kim
- Biosafety Research Institute and Laboratory of Pathology (BK21 Plus Program), College of Veterinary Medicine, Chonbuk National University, Iksan, Republic of Korea
| | - Hyeneui Jeong
- Biosafety Research Institute and Laboratory of Pathology (BK21 Plus Program), College of Veterinary Medicine, Chonbuk National University, Iksan, Republic of Korea
| | - Dong Gue Shin
- Research & Development Center of GENERAL BIO Co., Ltd, Namwon City, Jeollabuk-Do, Republic of Korea
| | - Jeong Hun Seo
- Research & Development Center of GENERAL BIO Co., Ltd, Namwon City, Jeollabuk-Do, Republic of Korea
| | - Jong Hoon Kim
- Biosafety Research Institute and Laboratory of Pathology (BK21 Plus Program), College of Veterinary Medicine, Chonbuk National University, Iksan, Republic of Korea
| | - Chae Woong Lim
- Biosafety Research Institute and Laboratory of Pathology (BK21 Plus Program), College of Veterinary Medicine, Chonbuk National University, Iksan, Republic of Korea
| | - Kang Min Han
- Department of Pathology, Dongguk University Ilsan Hospital, Goyang, Republic of Korea
| | - Bumseok Kim
- Biosafety Research Institute and Laboratory of Pathology (BK21 Plus Program), College of Veterinary Medicine, Chonbuk National University, Iksan, Republic of Korea
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16
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Qi HY, Li L, Ma H. Cellular stress response mechanisms as therapeutic targets of ginsenosides. Med Res Rev 2017; 38:625-654. [DOI: 10.1002/med.21450] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/26/2017] [Revised: 03/28/2017] [Accepted: 04/14/2017] [Indexed: 12/16/2022]
Affiliation(s)
- Hong-yi Qi
- College of Chinese Medicine; Southwest University; Chongqing P.R. China
| | - Li Li
- College of Chinese Medicine; Southwest University; Chongqing P.R. China
| | - Hui Ma
- College of Chinese Medicine; Southwest University; Chongqing P.R. China
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17
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Enhanced Production of Gypenoside LXXV Using a Novel Ginsenoside-Transforming β-Glucosidase from Ginseng-Cultivating Soil Bacteria and Its Anti-Cancer Property. Molecules 2017; 22:molecules22050844. [PMID: 28534845 PMCID: PMC6153937 DOI: 10.3390/molecules22050844] [Citation(s) in RCA: 34] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2017] [Revised: 05/07/2017] [Accepted: 05/12/2017] [Indexed: 11/16/2022] Open
Abstract
Minor ginsenosides, such as compound K, Rg3(S), which can be produced by deglycosylation of ginsenosides Rb1, showed strong anti-cancer effects. However, the anticancer effects of gypenoside LXXV, which is one of the deglycosylated shapes of ginsenoside Rb1, is still unknown due to the rarity of its content in plants. Here, we cloned and characterized a novel ginsenoside-transforming β-glucosidase (BglG167b) derived from Microbacterium sp. Gsoil 167 which can efficiently hydrolyze gypenoside XVII into gypenoside LXXV, and applied it to the production of gypenoside LXXV at the gram-scale with high specificity. In addition, the anti-cancer activity of gypenoside LXXV was investigated against three cancer cell lines (HeLa, B16, and MDA-MB231) in vitro. Gypenoside LXXV significantly reduced cell viability, displaying an enhanced anti-cancer effect compared to gypenoside XVII and Rb1. Taken together, this enzymatic method would be useful in the preparation of gypenoside LXXV for the functional food and pharmaceutical industries.
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18
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Massart J, Begriche K, Moreau C, Fromenty B. Role of nonalcoholic fatty liver disease as risk factor for drug-induced hepatotoxicity. J Clin Transl Res 2017; 3:212-232. [PMID: 28691103 PMCID: PMC5500243 DOI: 10.18053/jctres.03.2017s1.006] [Citation(s) in RCA: 50] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Obesity is often associated with nonalcoholic fatty liver disease (NAFLD), which refers to a large spectrum of hepatic lesions including fatty liver, nonalcoholic steatohepatitis (NASH) and cirrhosis. Different investigations showed or suggested that obesity and NAFLD are able to increase the risk of hepatotoxicity of different drugs. Some of these drugs could induce more frequently an acute hepatitis in obese individuals whereas others could worsen pre-existing NAFLD. AIM The main objective of the present review was to collect the available information regarding the role of NAFLD as risk factor for drug-induced hepatotoxicity. For this purpose, we performed a data-mining analysis using different queries including drug-induced liver injury (or DILI), drug-induced hepatotoxicity, fatty liver, nonalcoholic fatty liver disease (or NAFLD), steatosis and obesity. The main data from the collected articles are reported in this review and when available, some pathophysiological hypotheses are put forward. RELEVANCE FOR PATIENTS Drugs that could pose a potential risk in obese patients include compounds belonging to different pharmacological classes such as acetaminophen, halothane, methotrexate, rosiglitazone, stavudine and tamoxifen. For some of these drugs, experimental investigations in obese rodents confirmed the clinical observations and unveiled different pathophysiological mechanisms which could explain why these pharmaceuticals are particularly hepatotoxic in obesity and NAFLD. Other drugs such as pentoxifylline, phenobarbital and omeprazole might also pose a risk but more investigations are required to determine whether this risk is significant or not. Because obese people often take several drugs for the treatment of different obesity-related diseases such as type 2 diabetes, hyperlipidemia and coronary heart disease, it is urgent to identify the main pharmaceuticals that can cause acute hepatitis on a fatty liver background or induce NAFLD worsening.
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Affiliation(s)
- Julie Massart
- Department of Molecular Medicine and Surgery, Karolinska University Hospital, Karolinska Institutet, SE-171 77 Stockholm, Sweden
| | | | - Caroline Moreau
- INSERM, U991, Université de Rennes 1, Rennes, France.,Service de Biochimie et Toxicologie, CHU Pontchaillou, Rennes, France
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19
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Sesamin ameliorates hepatic steatosis and inflammation in rats on a high-fat diet via LXRα and PPARα. Nutr Res 2016; 36:1022-1030. [DOI: 10.1016/j.nutres.2016.06.015] [Citation(s) in RCA: 29] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2016] [Revised: 06/18/2016] [Accepted: 06/24/2016] [Indexed: 11/20/2022]
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20
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Zhou L, Zheng Y, Li Z, Bao L, Dou Y, Tang Y, Zhang J, Zhou J, Liu Y, Jia Y, Li X. Compound K Attenuates the Development of Atherosclerosis in ApoE(-/-) Mice via LXRα Activation. Int J Mol Sci 2016; 17:ijms17071054. [PMID: 27399689 PMCID: PMC4964430 DOI: 10.3390/ijms17071054] [Citation(s) in RCA: 31] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/14/2016] [Revised: 06/27/2016] [Accepted: 06/28/2016] [Indexed: 12/22/2022] Open
Abstract
Background: Atherosclerosis is a fundamental pathological process responded to some serious cardiovascular events. Although the cholesterol-lowering drugs are widely prescribed for atherosclerosis therapy, it is still the leading cause of death in the developed world. Here we measured the effects of compound K in atherosclerosis formation and investigated the probably mechanisms of the anti-antherosclerosis roles of compound K. Methods: We treated the atherosclerotic model animals (apoE−/− mice on western diet) with compound K and measured the size of atherosclerotic lesions, inflammatory cytokine levels and serum lipid profile. Peritoneal macrophages were collected in vitro for the foam cell and inflammasome experiments. Results: Our results show that treatment with compound K dose-dependently attenuates the formation of atherosclerotic plaques by 55% through activation of reverse cholesterol transport pathway, reduction of systemic inflammatory cytokines and inhibition of local inflammasome activity. Compound K increases the cholesterol efflux of macrophage-derived foam cells, and reduces the inflammasome activity in cholesterol crystal stimulated macrophages. The activation of LXRα may contribute to the athero-protective effects of compound K. Conclusion: These observations provide evidence for an athero-protective effect of compound K via LXRα activation, and support its further evaluation as a potential effective modulator for the prevention and treatment of atherosclerosis.
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Affiliation(s)
- Li Zhou
- Institute of Materia Medica and Department of Pharmaceutics, College of Pharmacy, Third Military Medical University, Shapingba, Chongqing 400038, China.
- Department of pharmacy, Xinqiao Hospital & The Second Affiliated Hospital, Third Military Medical University, Shapingba, Chongqing 400037, China.
| | - Yu Zheng
- Institute of Materia Medica and Department of Pharmaceutics, College of Pharmacy, Third Military Medical University, Shapingba, Chongqing 400038, China.
| | - Zhuoying Li
- Department of Outpatient, Logistical Engineering University of PLA, Shapingba, Chongqing 401311, China.
| | - Lingxia Bao
- Institute of Materia Medica and Department of Pharmaceutics, College of Pharmacy, Third Military Medical University, Shapingba, Chongqing 400038, China.
| | - Yin Dou
- Institute of Materia Medica and Department of Pharmaceutics, College of Pharmacy, Third Military Medical University, Shapingba, Chongqing 400038, China.
| | - Yuan Tang
- Institute of Materia Medica and Department of Pharmaceutics, College of Pharmacy, Third Military Medical University, Shapingba, Chongqing 400038, China.
| | - Jianxiang Zhang
- Institute of Materia Medica and Department of Pharmaceutics, College of Pharmacy, Third Military Medical University, Shapingba, Chongqing 400038, China.
| | - Jianzhi Zhou
- Institute of Materia Medica and Department of Pharmaceutics, College of Pharmacy, Third Military Medical University, Shapingba, Chongqing 400038, China.
| | - Ya Liu
- Institute of Materia Medica and Department of Pharmaceutics, College of Pharmacy, Third Military Medical University, Shapingba, Chongqing 400038, China.
| | - Yi Jia
- Institute of Materia Medica and Department of Pharmaceutics, College of Pharmacy, Third Military Medical University, Shapingba, Chongqing 400038, China.
| | - Xiaohui Li
- Institute of Materia Medica and Department of Pharmaceutics, College of Pharmacy, Third Military Medical University, Shapingba, Chongqing 400038, China.
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Kim MS, Ong M, Qu X. Optimal management for alcoholic liver disease: Conventional medications, natural therapy or combination? World J Gastroenterol 2016; 22:8-23. [PMID: 26755857 PMCID: PMC4698510 DOI: 10.3748/wjg.v22.i1.8] [Citation(s) in RCA: 39] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/28/2015] [Revised: 07/07/2015] [Accepted: 11/13/2015] [Indexed: 02/06/2023] Open
Abstract
Alcohol consumption is the principal factor in the pathogenesis of chronic liver diseases. Alcoholic liver disease (ALD) is defined by histological lesions on the liver that can range from simple hepatic steatosis to more advanced stages such as alcoholic steatohepatitis, cirrhosis, hepatocellular carcinoma and liver failure. As one of the oldest forms of liver injury known to humans, ALD is still a leading cause of liver-related morbidity and mortality and the burden is exerting on medical systems with hospitalization and management costs rising constantly worldwide. Although the biological mechanisms, including increasing of acetaldehyde, oxidative stress with induction of cytochrome p450 2E1, inflammatory cytokine release, abnormal lipid metabolism and induction of hepatocyte apoptosis, by which chronic alcohol consumption triggers serious complex progression of ALD is well established, there is no universally accepted therapy to prevent or reverse. In this article, we have briefly reviewed the pathogenesis of ALD and the molecular targets for development of novel therapies. This review is focused on current therapeutic strategies for ALD, including lifestyle modification with nutrition supplements, available pharmacological drugs and new agents that are under development, liver transplantation, application of complementary medicines, and their combination. The relevant molecular mechanisms of each conventional medication and natural agent have been reviewed according to current available knowledge in the literature. We also summarized efficacy vs safety on conventional and herbal medicines which are specifically used for the prevention and treatment of ALD. Through a system review, this article highlighted that the combination of pharmaceutical drugs with naturally occurring agents may offer an optimal management for ALD and its complications. It is worthwhile to conduct large-scale, multiple centre clinical trials to further prove the safety and benefits for the integrative therapy on ALD.
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Wei S, Li W, Yu Y, Yao F, A L, Lan X, Guan F, Zhang M, Chen L. Ginsenoside Compound K suppresses the hepatic gluconeogenesis via activating adenosine-5′monophosphate kinase: A study in vitro and in vivo. Life Sci 2015; 139:8-15. [DOI: 10.1016/j.lfs.2015.07.032] [Citation(s) in RCA: 36] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2015] [Revised: 07/27/2015] [Accepted: 07/29/2015] [Indexed: 02/04/2023]
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23
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Lu YF, Xu YY, Jin F, Wu Q, Shi JS, Liu J. Icariin is a PPARα activator inducing lipid metabolic gene expression in mice. Molecules 2014; 19:18179-91. [PMID: 25383754 PMCID: PMC6270773 DOI: 10.3390/molecules191118179] [Citation(s) in RCA: 38] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2014] [Revised: 10/12/2014] [Accepted: 10/13/2014] [Indexed: 01/06/2023] Open
Abstract
Icariin is effective in the treatment of hyperlipidemia. To understand the effect of icariin on lipid metabolism, effects of icariin on PPARα and its target genes were investigated. Mice were treated orally with icariin at doses of 0, 100, 200, and 400 mg/kg, or clofibrate (500 mg/kg) for five days. Liver total RNA was isolated and the expressions of PPARα and lipid metabolism genes were examined. PPARα and its marker genes Cyp4a10 and Cyp4a14 were induced 2-4 fold by icariin, and 4-8 fold by clofibrate. The fatty acid (FA) binding and co-activator proteins Fabp1, Fabp4 and Acsl1 were increased 2-fold. The mRNAs of mitochondrial FA β-oxidation enzymes (Cpt1a, Acat1, Acad1 and Hmgcs2) were increased 2-3 fold. The mRNAs of proximal β-oxidation enzymes (Acox1, Ech1, and Ehhadh) were also increased by icariin and clofibrate. The expression of mRNAs for sterol regulatory element-binding factor-1 (Srebf1) and FA synthetase (Fasn) were unaltered by icariin. The lipid lysis genes Lipe and Pnpla2 were increased by icariin and clofibrate. These results indicate that icariin is a novel PPARα agonist, activates lipid metabolism gene expressions in liver, which could be a basis for its lipid-lowering effects and its beneficial effects against diabetes.
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Affiliation(s)
- Yuan-Fu Lu
- Key Lab for Pharmacology of Ministry of Education, Department of Pharmacology, Zunyi Medical College, Zunyi 563003, China.
| | - Yun-Yan Xu
- Key Lab for Pharmacology of Ministry of Education, Department of Pharmacology, Zunyi Medical College, Zunyi 563003, China.
| | - Feng Jin
- Key Lab for Pharmacology of Ministry of Education, Department of Pharmacology, Zunyi Medical College, Zunyi 563003, China.
| | - Qin Wu
- Key Lab for Pharmacology of Ministry of Education, Department of Pharmacology, Zunyi Medical College, Zunyi 563003, China.
| | - Jing-Shan Shi
- Key Lab for Pharmacology of Ministry of Education, Department of Pharmacology, Zunyi Medical College, Zunyi 563003, China.
| | - Jie Liu
- Key Lab for Pharmacology of Ministry of Education, Department of Pharmacology, Zunyi Medical College, Zunyi 563003, China.
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