[Effect of Dendrobium officinale leaf-Citri Reticulatae Pericarpium extract on cholesterol metabolism in rats with...

This study aims to investigate the effects and underlying mechanisms of Dendrobium officinale leaf-Citri Reticulatae Pericarpium extract(DC) on cholesterol metabolism in the rat model of hypercholesterolemia. Sixty SD rats were randomly assigned to normal, model, ezetimibe(positive control, 1 mg·kg~(-1)), and low-, medium-, and high-dose(0.7, 1.4, and 2.8 g·kg~(-1), respectively) DC groups. A rat model of hypercholesterolemia was established via a high-fat diet(HFD). Throughout the 14-week modeling period, the rats received continuous oral interventions. General physical signs(including grip strength, autonomous activities, and dorsal temperature), blood rheology, and tail microcirculatory blood flow were monitored. Serum levels of total cholesterol(TC), low-density lipoprotein cholesterol(LDL-c), and aspartate aminotransferase(AST) were measured. Pathological changes in the liver and aortic tissue were assessed by hematoxylin-eosin(HE) and Masson staining. Hepatic levels of hydroxymethylglutaryl-coenzyme A reductase(HMGCR) and cholesterol 7α-hydroxylase(CYP7A1) were quantified. Furthermore, mRNA and protein levels of liver X receptor-α(LXR-α), low-density lipoprotein receptor(LDLR), and inducible degrader of LDLR(IDOL) were determined. The results demonstrated that DC significantly improved the grip strength and autonomous activities, reduced dorsal temperature and whole blood viscosity, and increased tail microcirculatory blood flow in the model rats. Furthermore, DC administration significantly lowered the serum levels of TC, LDL-c, and AST and ameliorated pathological alterations in the liver and aortic tissue. In addition, DC significantly lowered the hepatic HMGCR levels, while increasing the CYP7A1 level, suggesting modulation of both cholesterol synthesis and conversion pathways. DC upregulated the mRNA and protein levels of LDLR, concurrently downregulating those of LXR-α and IDOL. In conclusion, DC ameliorates hypercholesterolemia, potentially by regulating hepatic cholesterol metabolism via the LXR-α/IDOL/LDLR signaling pathway.