The COMPARATIVE PHARMACOLOGICAL EVALUATION OF DOLICHOS ACIPHYLLUS EXTRACT AND ITS LIPID-BASED FORMULATION IN EXPERIMENTAL HYPERLIPIDEMIA

Objective: The major aim of the current research work was to analyze the antihyperlipidemic and antioxidant efficacy of Dolichos aciphyllus extract (DAE) and its prepared lipid-based formulation (Dolichos aciphyllus extract-loaded nanostructured lipid carriers [DAENLCs]) against the high-fat diet (HFD)-induced hyperlipidemic rats. Methods: Antihyperlipidemic efficacy of DAE was analyzed initially by in vitro 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibition. HFD was used to induce hyperlipidemia in Wistar albino rats, followed by oral administration of DAE (400 mg/kg) and DAENLCs (400 mg/kg). The serum lipid parameters, such as cholesterol, triglycerides (TG), high-density lipoprotein (HDL), low-density lipoprotein (LDL), and very low-density lipoprotein (VLDL), were analyzed. Oxidative stress markers were determined by estimating malondialdehyde (MDA), reduced glutathione (GSH), superoxide dismutase (SOD), and catalase (CAT). Liver function markers, such as aspartate aminotransferase (AST) and alanine aminotransferase (ALT), were also assessed, along with histopathological changes in liver and adipose tissue, together with phytochemical screening and high-performance liquid chromatography (HPLC) fingerprinting for identifying the major phytochemical constituents. Results: The recent study showed that DAE and DAENLCs have marked in vitro HMG-CoA reductase inhibitor activity, followed by the lipid-based formulation showing greater inhibition than the pure extract. Treatment with a high dose of DAE and DAENLCs in HFD-induced hyperlipidemic rats showed a considerable reduction in the levels of serum total cholesterol, TG, LDL, VLDL, and atherogenic index while increasing the HDL levels when compared with the control group. The levels of AST and ALT, along with MDA levels, were also reduced considerably in the treatment groups when compared to the standard drug atorvastatin, while restoring the GSH, SOD, and CAT activities. The histopathological results showed improvement in the liver structure and morphology of adipose tissue in the treatment groups, where DAENLC demonstrated better protection of the tissue than DAE. The presence of quercetin in DAE was confirmed by the preliminary HPLC fingerprinting analysis by comparison with the standard quercetin. Conclusion: DAE showed potential antihyperlipidemia and antioxidant efficacy in hyperlipidemic rats, which was further increased when formulated in a lipid-based formulation. DAENLC showed improvement in lipid metabolism, oxidative stress, liver function, and alterations in liver architecture when compared with the pure extract. Thus, DAENLCs showed an enhanced pharmacological activity of Dolichos aciphyllus, which makes DAENLC a promising phyto-pharmaceutical strategy for treating hyperlipidemia and other metabolic disorders.