Total Iridoid Glycosides from Swertia mussotii Franch. Alleviate Cholestasis Induced by α-Naphthyl Isothiocyanate through Activating the Farnesoid X Receptor and Inhibiting Oxidative Stress

Cholestasis refers to a physiological and pathological process caused by bile acid (BA) overaccumulation inside the circulatory system and liver, leading to systemic and hepatocellular damage. Activating the farnesol X receptor (FXR) to restore BA homeostasis is a promising strategy for treating cholestasis. The objective of this research is to reveal solid evidence for the fact that the total iridoid glycosides from <i>Swertia mussotii</i> Franch. (IGSM) alleviate cholestasis. In this research, the whole plant of <i>S. mussotii</i> was extracted with 70% ethanol and separated by macroporous adsorption resin. A rat cholestasis model was established by the injection of α-naphthyl isothiocyanate (ANIT) at a dose of 75 mg/kg. Biochemical and oxidative stress indicators were determined using commercial assay kits. The mRNA abundance of FXR and target proteins was assessed using RT-qPCR. In addition, the effects of main compounds with FXR were evaluated by molecular docking after IGSM analysis using UPLC. The results indicated that IGSM alleviated ANIT-induced cholestasis through reducing serum ALT, AST, AKP, and TBA levels; increasing the mRNA levels of <i>Fxr</i>, <i>Besp</i>, <i>Ntcp</i>, and <i>Mep2</i>; and reducing oxidative stress. The proportion of iridoid compounds in IGSM exceeded 50%, which may be the active substance basis of IGSM. This study provides a theoretical reference for IGSM in the treatment of cholestasis, and future studies may delve more deeply into the FXR regulatory pathway.