Hypolipidemic Activity of Prosopis cineraria L (Druce) Fruit Extract and Molecular Modeling Study with Farnesoid X Receptor (FXR)

Abstract

Purpose: To investigate the hypolipidemic potential of the 70 % ethanol fruit extract of Prosopis cineraria (Fabaceae) (Et. PCF) in triton-induced hyperlipidemia in rats.Methods: Et-PCF was obtained by pulverizing whole dried fruits and extracting with 70 % ethanol. Adult Sprague Dawley rats were divided into six groups of six rats each. The groups were namely normal control, hyperlipidaemic control, standard drug-treated (simvastatin 4 mg/kg), and three Et-PCF (200, 400 and 600 mg/kg, respectively)-treated groups. Apart from normal control, all other groups received a single dose of triton (200 mg/kg, i.p.) exactly 30 min after a dose of the standard drug and Et-PCF for the induction of hyperlipidemia. Twenty four hours after trito  injection, hyperlipidemia was confirmed by collecting blood samples from all the rats and testing for serum lipid profile. Antioxidant activity, in the form of inhibition of lipid peroxidation, was determined along with chromatographic analysis. Moreover, molecular docking study of â-sitosterol (active constitute of PCF) was performed with Farnesoid X receptor.Results: Triton-induced hyperlipidemia group showed significant increase in total cholesterol, low density lipoprotein cholesterol (LDL), very low density  lipoprotein cholesterol (VLDL) , triglyceride, atherogenic index and decreased high density lipoprotein cholesterol (HDL), compared to normal control group. Et-PCF treated groups showed reduction in serum cholesterol, triglyceride, VLDL and LDL levels compared to triton treated control group. Extract at the dose of 200 mg/kg significantly reduce serum cholesterol (p < 0.01) and serum LDL (p < 0.01). At the dose level of 400 mg/kg and 600 mg/kg extract is effective to significantly  reduce serum cholesterol (p < 0.05), triglyceride (p < 0.05), VLDL (p < 0.05), LDL (p < 0.05) and atherogenic index (p < 0.05) and these results are almost  equivalent to those of standard drug simvastatin. Furthermore, antioxidant activity, i.e., IC50 of Et-PCF was 58.33 ±g/ml. Molecular docking score of â-sitosterol for Farnesoid X receptor was -8.32 kcal/mol, suggesting excellent binding conformation of Et-PCF to receptor molecules.Conclusion: The findings suggest that Prosopis cineraria may be beneficial for preventing hyperlipidaemic complications by its anti-hyperlipidemic and antioxidant activities.Keywords: Prosopis cineraria, Anti-hyperlipidemic activity, Simvastatin, Triton, Docking studies, Farnesoid X receptor