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Calycosin attenuates triglyceride accumulation and hepatic fibrosis in murine model of non-alcoholic steatohepatitis via activating farnesoid X receptor.
Phytomedicine. 2017 Feb 15; 25:83-92.P

Abstract

BACKGROUND

Non-alcoholic steatohepatitis (NASH) represents the more severe end of hepatic steatosis and is associated with progressive liver disease. Calycosin, derived from the root of Radix Astragali, has been demonstrated to have favorable efficacy on acute liver injury.

PURPOSE

The present study was to investigate the hepatoprotective effect of calycosin on attenuating triglyceride accumulation and hepatic fibrosis, as well as explore the potential mechanism in murine model of NASH.

STUDY DESIGN

The C57BL/6 male mice were fed with methionine choline deficient (MCD) diet for 4 weeks to induce NASH and treated with or without calycosin by oral gavage for 4 weeks.

METHODS

The body weight, liver weight and the liver to body weight ratios were measured. Serum ALT, AST, TG, TC, FFA, MCP-1 and mKC levels were accessed by biochemical methods. H&E staining and Oil red O staining were used to identify the amelioration of liver histopathology. Immunohistochemistry of a-SMA, Masson trichrome staining and Sirius red staining were used to identify the amelioration of hepatic fibrosis. The quantitative real-time-PCR and Western blot were applied to observe the expression changes of key factors involved in triglyceride synthesis, free fatty acid β-oxidation and hepatic fibrosis.

RESULTS

Calycosin significantly inhibited body weight loss induced by MCD diet, decreased the ALT and AST activities, MCP-1 and mKC in a dose-dependent manner. The H&E and Oil red O staining indicated calycosin effectively improved hepatic steatosis, improved the degree of triglyceride accumulation. Masson trichrome and Sirius red staining indicated that calycosin treatment remarkably attenuated the degree of hepatic fibrosis. Immunohistochemistry of a-SMA demonstrated that calycosin attenuated hepatic fibrosis by inhibiting hepatic stellate cell activation. Further, calycosin inhibited the expression of SREBP-1c, FASN, ACC and SCD1 involved in triglyceride synthesis, promoted the expression of PPARa, CPT1, Syndecan-1 and LPL involved in free fatty acid β-oxidation. The above effects of calycosin were attributed to FXR activation.

CONCLUSION

Calycosin attenuates triglyceride accumulation and hepatic fibrosis to protect against NASH via FXR activation.

Authors+Show Affiliations

Department of Clinical Pharmacology, College of Pharmacy, Dalian Medical University, 9 West Section, Lvshun South Road, Lvshunkou District, Dalian, Liaoning, China; Provincial Key Laboratory for Pharmacokinetics and Transport, Dalian, Liaoning, China.Department of Clinical Pharmacology, College of Pharmacy, Dalian Medical University, 9 West Section, Lvshun South Road, Lvshunkou District, Dalian, Liaoning, China; Provincial Key Laboratory for Pharmacokinetics and Transport, Dalian, Liaoning, China. Electronic address: mengq531@163.com.Department of Clinical Pharmacology, College of Pharmacy, Dalian Medical University, 9 West Section, Lvshun South Road, Lvshunkou District, Dalian, Liaoning, China; Provincial Key Laboratory for Pharmacokinetics and Transport, Dalian, Liaoning, China.Department of Clinical Pharmacology, College of Pharmacy, Dalian Medical University, 9 West Section, Lvshun South Road, Lvshunkou District, Dalian, Liaoning, China; Provincial Key Laboratory for Pharmacokinetics and Transport, Dalian, Liaoning, China.Department of Clinical Pharmacology, College of Pharmacy, Dalian Medical University, 9 West Section, Lvshun South Road, Lvshunkou District, Dalian, Liaoning, China; Provincial Key Laboratory for Pharmacokinetics and Transport, Dalian, Liaoning, China.Department of Clinical Pharmacology, College of Pharmacy, Dalian Medical University, 9 West Section, Lvshun South Road, Lvshunkou District, Dalian, Liaoning, China; Provincial Key Laboratory for Pharmacokinetics and Transport, Dalian, Liaoning, China.Department of Clinical Pharmacology, College of Pharmacy, Dalian Medical University, 9 West Section, Lvshun South Road, Lvshunkou District, Dalian, Liaoning, China.Department of Clinical Pharmacology, College of Pharmacy, Dalian Medical University, 9 West Section, Lvshun South Road, Lvshunkou District, Dalian, Liaoning, China; Provincial Key Laboratory for Pharmacokinetics and Transport, Dalian, Liaoning, China.Department of Clinical Pharmacology, College of Pharmacy, Dalian Medical University, 9 West Section, Lvshun South Road, Lvshunkou District, Dalian, Liaoning, China.Department of Clinical Pharmacology, College of Pharmacy, Dalian Medical University, 9 West Section, Lvshun South Road, Lvshunkou District, Dalian, Liaoning, China; Provincial Key Laboratory for Pharmacokinetics and Transport, Dalian, Liaoning, China.Department of Clinical Pharmacology, College of Pharmacy, Dalian Medical University, 9 West Section, Lvshun South Road, Lvshunkou District, Dalian, Liaoning, China; Provincial Key Laboratory for Pharmacokinetics and Transport, Dalian, Liaoning, China. Electronic address: kexinliu@dlmedu.edu.cn.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

28190475

Citation

Duan, Xingping, et al. "Calycosin Attenuates Triglyceride Accumulation and Hepatic Fibrosis in Murine Model of Non-alcoholic Steatohepatitis Via Activating Farnesoid X Receptor." Phytomedicine : International Journal of Phytotherapy and Phytopharmacology, vol. 25, 2017, pp. 83-92.
Duan X, Meng Q, Wang C, et al. Calycosin attenuates triglyceride accumulation and hepatic fibrosis in murine model of non-alcoholic steatohepatitis via activating farnesoid X receptor. Phytomedicine. 2017;25:83-92.
Duan, X., Meng, Q., Wang, C., Liu, Z., Liu, Q., Sun, H., Sun, P., Yang, X., Huo, X., Peng, J., & Liu, K. (2017). Calycosin attenuates triglyceride accumulation and hepatic fibrosis in murine model of non-alcoholic steatohepatitis via activating farnesoid X receptor. Phytomedicine : International Journal of Phytotherapy and Phytopharmacology, 25, 83-92. https://doi.org/10.1016/j.phymed.2016.12.006
Duan X, et al. Calycosin Attenuates Triglyceride Accumulation and Hepatic Fibrosis in Murine Model of Non-alcoholic Steatohepatitis Via Activating Farnesoid X Receptor. Phytomedicine. 2017 Feb 15;25:83-92. PubMed PMID: 28190475.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Calycosin attenuates triglyceride accumulation and hepatic fibrosis in murine model of non-alcoholic steatohepatitis via activating farnesoid X receptor. AU - Duan,Xingping, AU - Meng,Qiang, AU - Wang,Changyuan, AU - Liu,Zhihao, AU - Liu,Qi, AU - Sun,Huijun, AU - Sun,Pengyuan, AU - Yang,Xiaobo, AU - Huo,Xiaokui, AU - Peng,Jinyong, AU - Liu,Kexin, Y1 - 2016/12/13/ PY - 2016/07/07/received PY - 2016/11/28/revised PY - 2016/12/12/accepted PY - 2017/2/14/entrez PY - 2017/2/14/pubmed PY - 2017/5/18/medline KW - Calycosin KW - Farnesoid X receptor KW - Hepatic fibrosis KW - Non-alcoholic steatohepatitis KW - Triglyceride accumulation SP - 83 EP - 92 JF - Phytomedicine : international journal of phytotherapy and phytopharmacology JO - Phytomedicine VL - 25 N2 - BACKGROUND: Non-alcoholic steatohepatitis (NASH) represents the more severe end of hepatic steatosis and is associated with progressive liver disease. Calycosin, derived from the root of Radix Astragali, has been demonstrated to have favorable efficacy on acute liver injury. PURPOSE: The present study was to investigate the hepatoprotective effect of calycosin on attenuating triglyceride accumulation and hepatic fibrosis, as well as explore the potential mechanism in murine model of NASH. STUDY DESIGN: The C57BL/6 male mice were fed with methionine choline deficient (MCD) diet for 4 weeks to induce NASH and treated with or without calycosin by oral gavage for 4 weeks. METHODS: The body weight, liver weight and the liver to body weight ratios were measured. Serum ALT, AST, TG, TC, FFA, MCP-1 and mKC levels were accessed by biochemical methods. H&E staining and Oil red O staining were used to identify the amelioration of liver histopathology. Immunohistochemistry of a-SMA, Masson trichrome staining and Sirius red staining were used to identify the amelioration of hepatic fibrosis. The quantitative real-time-PCR and Western blot were applied to observe the expression changes of key factors involved in triglyceride synthesis, free fatty acid β-oxidation and hepatic fibrosis. RESULTS: Calycosin significantly inhibited body weight loss induced by MCD diet, decreased the ALT and AST activities, MCP-1 and mKC in a dose-dependent manner. The H&E and Oil red O staining indicated calycosin effectively improved hepatic steatosis, improved the degree of triglyceride accumulation. Masson trichrome and Sirius red staining indicated that calycosin treatment remarkably attenuated the degree of hepatic fibrosis. Immunohistochemistry of a-SMA demonstrated that calycosin attenuated hepatic fibrosis by inhibiting hepatic stellate cell activation. Further, calycosin inhibited the expression of SREBP-1c, FASN, ACC and SCD1 involved in triglyceride synthesis, promoted the expression of PPARa, CPT1, Syndecan-1 and LPL involved in free fatty acid β-oxidation. The above effects of calycosin were attributed to FXR activation. CONCLUSION: Calycosin attenuates triglyceride accumulation and hepatic fibrosis to protect against NASH via FXR activation. SN - 1618-095X UR - https://www.unboundmedicine.com/medline/citation/28190475/Calycosin_attenuates_triglyceride_accumulation_and_hepatic_fibrosis_in_murine_model_of_non_alcoholic_steatohepatitis_via_activating_farnesoid_X_receptor_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0944-7113(16)30253-7 DB - PRIME DP - Unbound Medicine ER -