Integrated network pharmacology, transcriptomics and metabolomics to explore the material basis and mechanism of Danggui-Baishao herb pair for treating hepatic fibrosis

Ethnopharmacological relevance: The Danggui-Baishao herb pair (DB) is commonly used as Chinese herbal formulas for treating hepatic fibrosis (HF). However, there are few research on the combined application of the two drugs in treating HF, and the precise mechanisms and fundamental components of DB in addressing HF are still unclear. Aim of the study: The intention of this research is to identify the molecular foundation and functional targets of DB to elucidate the mechanisms for treating HF. Methods: The ingredients absorbed from DB in rat plasma were analyzed using UPLC-QE-MS. Therapeutic efficacy of DB in a rat model of CCl4-induced HF assessed using biochemical indices, pathological tissue observations, immunohistochemical and western blotting. An integrated strategy of transcriptomics, metabolomics, and network pharmacology was then utilized to explain the possible material basis and mechanisms of DB for treating HF. Western blotting was carried out to verify the critical mechanism. Results: DB reduced the level of liver function and inflammation related indicators in CCl4-induced HF (P < 0.05 or P < 0.01), as well as ameliorated pathological histological changes, and reduced the expressions of collagen type I (Col-I) and alpha-smooth muscle actin (alpha-SMA). Nineteen ingredients absorbed from DB were identified. Comprehensive investigations of transcriptomics, metabolomics, and network pharmacology revealed that DB modulated the PI3K/Akt/NF-kappa B signaling pathway to ameliorate fibrosis induced by CCl4 in HF rats. According to the molecular docking results, core tagets were highly favored by kaempferol, benzoylpaeoniflorin, albiflorin, paeoniflorin, and levistilide A. Conclusions: The possible mechanisms for DB treatment of HF include decreasing the activity of hepatic stellate cells (HSCs), decreasing collagen synthesis and deposition, attenuating the hepatic inflammatory response, inhibiting hepatocyte apoptosis, and increasing the level of niacinamide (NAM), thus exerting its anti-HF effect.