ETHNOPHARMACOLOGICAL RELEVANCE: Non-alcoholic fatty liver disease (NAFLD) has been a chronic liver disease with increasing morbidity in the past 20 years. Chinese herb pairs are the fundamental and streamlined instances of traditional Chinese medicine (TCM) prescriptions that effectively interpret their underlying concepts. Bupleuri Radix (Chaihu)-Scutellariae Radix (Huangqin) herb pair (CHHQ) is a renowned herb pair that has been frequently used in TCM prescriptions for treating NAFLD. Nevertheless, the effect and mechanism of CHHQ in alleviating NAFLD are currently unclear.
AIM OF THE STUDY: To evaluate the effect, potential targets, and underlying molecular mechanisms of CHHQ in NAFLD by integrating transcriptomics, metabolomics, network pharmacology, and experiments in vivo and in vitro.
MATERIALS AND METHODS: UHPLC-MS/MS was used to identify the CHHQ aqueous extract and drug-containing serum. A high-fat diet, glucose-fructose water-induced NAFLD mice, and free fatty acid induced Aml12 and HepG2 cells were used to evaluate the effect of CHHQ in NAFLD. Transcriptomics, metabolomics, network pharmacology, and molecular biology experiments were used to explore the underlying mechanisms.
RESULTS: CHHQ markedly alleviated NAFLD by reducing hepatic steatosis and protecting the liver in vivo and in vitro. Non-targeted metabolomics indicated that CHHQ decreased hepatic lipid in NAFLD mice; network pharmacology and transcriptomics predicted that the potential mechanism was interlinked with β-oxidation and the PPARA pathway. Mechanistically, CHHQ increased the expression of PPARA, CPT1A, and ACOX1, which was further corroborated by co-incubation with agonists and inhibitors of PPARA.
CONCLUSIONS: CHHQ alleviates NAFLD in regulating intrahepatic lipid metabolism via PPARA/CPT1A/ACOX1, which provided critical evidence to energize the investigation of CHHQ-based therapies for treating NAFLD.
