Diosgenin alleviates hypercholesterolemia via SRB1/CES-1/CYP7A1/FXR pathway in high-fat diet-fed rats.

Diosgenin alleviates hypercholesterolemia via SRB1/CES-1/CYP7A1/FXR pathway in high-fat diet-fed rats. Toxicol Appl Pharmacol. 2020 Dec 28;:115388 Authors: Yu L, Lu H, Yang X, Li R, Shi J, Yu Y, Ma C, Sun F, Zhang S, Zhang F Abstract Phytosterol diosgenin (DG) exhibits cholesterol-lowering properties. Few studies focused on the underlying mechanism of DG attenuation of hypercholesterolemia by promoting cholesterol metabolism. To investigate the roles of SRB1/CES-1/CYP7A1/FXR pathways in accelerating cholesterol elimination and alleviating hypercholesterolemia, a rat model of hypercholesterolemia was induced by providing a high-fat diet (HFD). Experimental rat models were randomly divided into a normal control (Con) group, HFD group, low-dose DG (LDG) group (150 mg/kg/d), high-dose DG (HDG) group (300 mg/kg) and Simvastatin (Sim) group (4 mg/kg/d). Body weights, serum and hepatic lipid parameters of rats were tested. The expression levels of scavenger receptor class B type I (SRB1), carboxylesterase-1 (CES-1), cholesterol7α- hydroxylase (CYP7A1), and farnesoid X receptor (FXR) were determined. The results showed that DG reduced weight and lowered lipid levels in HFD-fed rats. Pathological morphology analyses revealed that DG notably improved hepatic steatosis and intestinal structure. Further studies showed the increased hepatic SRB1, CES-1, CYP7A1 and inhibited FXR-mediated signaling in DG-fed rats, which contributing to the d...
Source: Toxicology and Applied Pharmacology - Category: Toxicology Authors: Tags: Toxicol Appl Pharmacol Source Type: research