Effect of Pure Total Flavonoids from Citrus on Hepatic SIRT1/PGC-1α Pathway in Mice with NASH

CHEN Zhiyun 1 LI Jianshuan1 JIANG Jianping1 YAN Maoxiang1 HE Beihui1

(1.Zhejiang Provincial Hospital of Traditional Chinese Medicine, the 1st Clinical Medical College of Zhejiang, Hangzhou 310006)
【Novelty】These These After the intervention with different doses of PTFC, the NAFLD activity scores, the content of TG and the level of AST in serum were notably lower than that of the normal group; whereas the SIRT1,PGC-1α, MnSOD mRNA and protein expression were obviously higher than that of the normal group,with the significant decrease in the expression of 8-OHdG and the content of MDA. Oxidative stress /lipid peroxidation enhancement in in NASH mice induced by high-fat diet may be related to the changes in SIRT1/PGC-1α signal transduction pathway. PTFC could enhance the anti-oxidant capacity in liver, relieve the damage of reactive oxygen during the fatty acid metabolic process, and prevent NASH from the occurrenceand development by regulating the SIRT1/PGC-1α signal pathway.

【Abstract】Objective: To observe the effect of pure total flavonoids from Citrus (PTFC) on the hepatic fatty degen-eration,inflammation,oxidative stress and SIRT1/PGC-1α expressions in mice with non-alcohol steatohepatitis (NASH), and discuss the action mechanism of PTFC on NASH. Method: Mice were given high-fat diet for 16 weeks to induce the NASH model. Since the seventh week after the model establishment,the mice were intervened with 100, 50 and 25 mg·kg -1·d -1 PTFC for 10 weeks. The pathologic changes in hepatic tissues were observed with HE staining. The contents of TG,CHOL in hepatic tissue,as well as the levels of AST,ALT in serum were detected by using the biochemical process. The expression of SIRT1,PGC-1α and MnSOD mRNA in hepatic tissues were detected with Real-time PCR assay. SIRT1,PGC-1α protein and 8-OHdG expressions were determined with the immunohistochemical method. The SOD level in hepatic tissues was tested by the xanthine oxidase method. The MDA content in hepatic tissues was examined by the thiobarbituric acid method. Result: The contents of TG,CHOL,NAFLD activity scores and ALT level in serum in hepatic tissues of mice in the model induced by fat-rich diet were remarkably higher than that of the control group (P < 0.01). The SIRT1,PGC-1α,MnSOD mRNA and protein expression in hepatic tissues were significantly lower than that of the control group (P < 0.01). The expres-sion of 8-OHdG and the content of MDA in hepatic tissues were significantly higher than that of the control group (P < 0.01). After the intervention with different doses of PTFC,the NAFLD activity scores,the content of TG and the level of AST in serum were notably lower than that of the control group (P < 0.01,P < 0.05); whereas the SIRT1,PGC-1α,MnSOD mRNA and protein expression were remarkably higher than that of the control group (P < 0.01,P < 0.05),with the significant decrease in the expression of 8-OHdG and the content of MDA (P < 0.01). Conclusion: Oxidative stress/lipid peroxidation enhancement in NASH mice induced by high-fat diet may be relat-ed to the changes in SIRT1/PGC-1α signal transduction pathway. PTFC could enhance the anti-oxidant capacity in liver,relieve the damage of reactive oxygen during the fatty acid metabolic process,and prevent NASH from the occurrence and development by regulating the SIRT1/PGC-1α signal pathway.

【Keywords】 Non-alcoholic Steatohepatitis; Oxidative Stress; SIRT1; PGC-1α; Pure Total Flavonoids from Citrus;

【DOI】

【Funds】 Zhejiang Provincial Natural Science Foundation (Grant No. LY13H290011) Zhejiang Province Traditional Chinese Medicine Scientific Re-search Project (Grant No. 2013ZA047)

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This Article

ISSN:1001-5302

CN: 11-2272/R

Vol 39, No. 01, Pages 100-105

January 2014

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Abstract

  • 1 Materials
  • 2 Methods
  • 3 Results
  • 4 Discussion
  • References