Mechanic study of Qushi Kaiyu decoction on non-alcoholic fatty liver disease model rats based on the inhibition of TLR4/NF-ĸB pathway

Abstract

Background: The objective of this research was to examine the impact of the Chinese herbal formula Qushi Kaiyu (QSKY) on rats with non-alcoholic fatty liver disease (NAFLD) and its inhibitory effect on the TLR4/NF-ĸB pathway. Methods: NAFLD model rats was constructed through high-fat diet. Meanwhile, rats were treated with QSKY (6.4 g/kg) by gavage. The therapeutic effect of QSKY on NAFLD was assessed by testing body weight change, the liver index, lipid concentrations in blood, and antioxidant and inflammatory levels; assessing liver function; and performing pathological staining including hematoxylin-eosin and Oil Red O. The protein levels of key factors in the TLR4/NF-ĸB pathway (TLR4, MyD88, p65 and IKB) in rat liver tissue were determined using western blotting in order to explore the mechanism responsible for the therapeutic effects of QSKY in rats with NAFLD. Results: QSKY significantly reduced the liver index and body weight value; reduced triglyceride, cholesterol, alanine aminotransferase, and aspartate aminotransferase levels in NAFLD rats; improved the pathological changes, such as ballooning degeneration, fat accumulation, necrosis, and inflammation; elevated GSH-Px and superoxide dismutase activities and lowered malondialdehyde levels, indicating that QSKY enhanced the antioxidant capacity; and reduced inflammatory cytokine (IL-6, IL-1β, and TNF-α) levels. Western blotting results showed that QSKY significantly reduced TLR4, MyD88, and decreased the phosphorylation of IKB and p65 protein levels in the livers of rats with NAFLD. Conclusions: QSKY showed therapeutic effects on NAFLD and can alleviate oxidative stress and inflammation. This mechanism may be related to an improvement in TLR4/NF-ĸB pathway.