Huangqin decoction mitigates hepatic inflammation in high-fat diet-challenged rats by inhibiting TLR4/NF-κB/NLRP3 pathway.

ABSTRACT

ETHNOPHARMACOLOGICAL RELEVANCE Non-alcoholic fatty liver disease (NAFLD) has become the most common chronic hepatopathy worldwide, in which ectopic steatosis (5%) and inflammatory infiltration in the liver are the principal clinical characteristics. Huangqin decoction (HQD), a Chinese medicine formula used in the clinic for thousands of years, presents appreciable anti-inflammatory effects. Nevertheless, the role and mechanism of HQD against inflammation in NAFLD are still undefined. AIM OF THE STUDY The objective of this study was to evaluate the curative efficacy and unravel the involved mechanism of HQD on a high-fat diet (HFD)-induced NAFLD. MATERIALS AND METHODS: First, HPLC was utilized to analyze the main chemical components of HQD. Then, NAFLD model was introduced by subjecting the rats to HFD for 16 weeks, and HQD (400 and 800 mg/kg) or polyene lecithin choline (PLC, 8 mg/kg) was given orally from week 8-16. Pharmacodynamic indicators including body weight, liver weight, liver index, as well as biochemical and histological parameters were assessed. As to mechanism exploration, the expressions of TLR4/NF-κB/NLRP3 pathway and molecular docking between major phytochemicals of HQD and key targets of TLR4/NF-κB/NLRP3 pathway were investigated. RESULTS: Seven main monomeric constituents of HQD were revealed by HPLC analysis. Of note, HQD could effectively attenuate the body weight, liver weight, and liver index, rescue disorders in serum transaminases and lipid profile, correct hepatic histological abnormalities, and reduce phagocytes infiltration into the liver and pro-inflammatory cytokines release in NAFLD rats. Mechanism investigation discovered that HQD harbored inhibitory effects on TLR4/NF-κB/NLRP3 pathway-regulated liver inflammation. Further exploration found that seven phytochemicals in HQD exhibited better binding modes with TLR4/NF-κB/NLRP3 pathway, in which baicalein, baicalin and liquiritin presented the highest affinity and docking score for protein TLR4, NF-κB, and NLRP3, respectively. CONCLUSIONS: These findings confirmed that HQD ameliorated hepatic inflammation in NAFLD rats by blocking the TLR4/NF-κB/NLRP3 pathway, with multi-components and multi-targets action pattern.