JianPi-QingHua formula attenuates nonalcoholic fatty liver disease by regulating the AMPK/SIRT1/NF-κB pathway in high-fat-diet-fed C57BL/6 mice

Pharm Biol. 2023 Dec;61(1):647-656. doi: 10.1080/13880209.2023.2188549.

Abstract

Context: Non-alcoholic fatty liver disease (NAFLD) is a common liver disease, accompanied by liver lipid accumulation and inflammation. JianPi-QingHua formula (JPQH), a Chinese herbal formula, exhibits effects on obesity and T2DM. However, the hepatoprotective effect of JPQH has not been elucidated.

Objective: To investigate the hepatoprotective effect of JPQH in NAFLD induced by a high-fat diet (HFD) in mice.

Materials and methods: C57BL/6J mice were divided into four groups and fed a normal-fat diet (ND), high-fat diet (HFD), HFD + JPQH (2.5 g/kg), or HFD + metformin (300 mg/kg) for 6 weeks, respectively. Furthermore, the body weight, epididymal fat mass, blood glucose, and liver weight were measured. Serum total cholesterol (TC), triglycerides (TG), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) were performed. Hematoxylin and eosin staining and Oil Red O staining were observed in hepatic histopathological changes. Western blotting and quantitative real-time polymerase chain reaction were utilized to assess the key protein expression of hepatic lipid metabolism and inflammation.

Results: Compared with the HFD group, JPQH could reduce body weight, epididymal fat mass, blood glucose and liver weight (p < 0.05), and markedly decreased the levels of serum TC, TG, ALT, AST (p < 0.05). Additionally, JPQH improved liver pathological changes. Consistent with the hepatic histological analysis, JPQH intervention suppressed lipid accumulation and inflammatory responses. Mechanistically, JPQH boosted SIRT1/AMPK signalling, and attenuated NF-κB pathway, which suppressed inflammatory responses.

Discussion and conclusions: These findings indicate that JPQH supplementation protected against HFD-induced NAFLD by regulating SIRT1/AMPK/NF-κB pathway, which provides a theoretical basis for the clinical treatment of patients with NAFLD.

Keywords: NAFLD induced by HFD; hepatic inflammation; hepatic lipid accumulation.

MeSH terms

  • AMP-Activated Protein Kinases / metabolism
  • Animals
  • Blood Glucose / metabolism
  • Diet, High-Fat / adverse effects
  • Inflammation / drug therapy
  • Inflammation / metabolism
  • Inflammation / prevention & control
  • Liver
  • Mice
  • Mice, Inbred C57BL
  • NF-kappa B / metabolism
  • Non-alcoholic Fatty Liver Disease* / drug therapy
  • Non-alcoholic Fatty Liver Disease* / etiology
  • Non-alcoholic Fatty Liver Disease* / prevention & control
  • Obesity / metabolism
  • Sirtuin 1 / metabolism
  • Triglycerides / metabolism

Substances

  • NF-kappa B
  • AMP-Activated Protein Kinases
  • Sirtuin 1
  • Blood Glucose
  • Triglycerides
  • Sirt1 protein, mouse

Grants and funding

This work was supported by the National Natural Science Foundation of China [No.82074381 and 81874434], Shanghai Key Laboratory of Chinese Medicine Clinical Medicine [No.20DZ2272200], Shanghai Municipal Key Clinical Specialty [No.shslczdzk05401], Shanghai University of Traditional Chinese Medicine Science and Technology Innovation Project [No.YYKC-2021-01-144] and Scientific Research Program of Shanghai Science and Technology Commission [No.21S21900700].