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

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 lipid accumulation
• hepatic inflammation

Author contributions

Xu Han and Hao Lu designed and supervised the study. Jing Tian and Mengjie Cai performed the experiments. Jing Tian, Shenyi Jin, Qingguang Chen, Jiahui Xu, Qiuyue Guo and Zihui Yan participated in analyzing data. Jing Tian and Mengjie Cai wrote the manuscript.

Disclosure statement

The authors report no conflict of interest.

Additional information

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].