The water extract of Sophorae tonkinensis Radix et Rhizoma alleviates non-alcoholic fatty liver disease and its mechanism

Abstract

Background: Sophorae tonkinensis Radix et Rhizoma is traditionally used for clearing away heat and toxic materials in China.

Purpose: This study aims to observe the amelioration of Sophorae tonkinensis water extract (STR) against non-alcoholic fatty liver disease (NAFLD) and the engaged mechanism.

Methods: NAFLD was induced in mice fed by methionine and choline deficient (MCD) diet. Liver histological observation, Oil Red O, Masson's trichrome and F4/80 immunohistochemical staining were performed. Serum and liver biochemical parameters, hepatic gene and protein expression were detected. Cellular lipids accumulation in human normal liver l-02 and hepatoma HepRG cells were induced by 0.5 mM nonestesterified fatty acid (NEFA). The contents of matrine (MT) and oxymatrine (OMT) in STR were detected by using high-performance liquid chromatography (HPLC). Carnitine palmitoyltransferase 1A (CPT1A) expression and enzymatic activity were detected both in vivo and in vitro.

Results: Serum alanine/aspartate aminotransferase (ALT/AST) activity, hepatic malondialdehyde (MDA) content and liver histological observation showed that STR alleviated hepatocellular damage in mice fed with MCD diet. Hepatic triglyceride (TG), total cholesterol (TC) and NEFA amounts, and Oil Red O staining showed that STR reduced hepatic lipids accumulation in mice fed with MCD diet. STR and its main compounds including MT and OMT decreased NEFA-induced cellular lipids accumulation in hepatocytes. STR enhanced CPT1A activity both in vivo and in vitro. MT and OMT also enhanced cellular CPT1A activity in l-02 hepatocytes treated with NEFA. Moreover, the CTP1A inhibitor etomoxir (ETO) reduced the lipid-lowering activity provided by STR, MT or OMT in vitro. Liver myeloperoxidase (MPO) activity and hydroxyproline content, Masson's trichrome and F4/80 immunohistochemical staining, and hepatic mRNA expression of some molecules involved in regulating inflammation or fibrosis demonstrated that STR alleviated hepatic inflammation and liver fibrosis in mice fed with MCD diet.

Conclusion: STR alleviated NAFLD by inhibiting hepatic inflammation and liver fibrosis, and reducing hepatic lipids accumulation through promoting fatty acids β-oxidation by enhancing liver CPT1A activity. MT and OMT may be the main active compounds contributing to the lipid-lowering activity provided by STR.

Keywords: CPT1A; Inflammation; MCD; NAFLD; STR.