Hypolipidemic and HMG-CoA reductase inhibitory effects of 15-oxoursolic acid from Rhododendron arboreum: An In-vivo and In-silico study.

Abstract

Background: Hyperlipidemia is an identified risk factor for metabolic syndrome, obesity and cardiovascular complications characterized by elevated levels of lipids in blood.

Objective: The present study aimed to inhibit HMG-CoA reductase with 15-oxoursolic acid through in-vivo and in-silico assessments.

Methods: The amorphous compound 15-oxoursolic acid was obtained from plant material through purification with a rotary evaporator and column chromatography. The male BALB/c mice were maintained under stabilized ambient conditions and sustained with standard food and water ad libitum. HFD was used to induce hyperlipidemia in rats.

Results: HFD-induced hyperlipidemia in rats was developed with a marked increase in total cholesterol (58.34 ± 0.21 mg/dL), triglycerides (45.45 ± 0.39 mg/dL), LDL-c (66.12 ± 0.10 mg/dL), VLDL-c (19.34 ± 0.16 mg/dL), and a decrease in HDL-c (10.34 ± 0.18 mg/dL). The oral administration of 15-oxoursolic acid at a concentration of 30 mg/Kg b.w significantly reduced the serum concentration of total cholesterol (42.65 ± 0.54 mg/dL), triglycerides (32.33 ± 0.16 mg/dL), LDL-c (50.34 ± 0.15 mg/dL) and VLDL-c (13.15 ± 0.45 mg/dL), respectively and an increased in the serum HDL-c (18.56 ± 0.34 mg/dL). 15-oxoursolic acid also caused a decrease in the coronary risk index and atherogenic risk index. In-silico studies of 15-oxoursolic acid with HMG-CoA reductase showed significant interaction capability with binding energy (-9.26805 Kcal/mol).

Conclusions: It is concluded that 15-oxoursolic acid could significantly reduce the total cholesterol, triglycerides and LDL levels in HFD-induced hyperlipidemia rats, which might lead to new medication with significant hypolipidemic potential.