Ficus elastica phytochemicals mitigate hyperlipidemia via potential HMG-CoA reductase inhibition, reduced oxidative stress, and tissue preservation

Background and purpose: Hyperlipidemia remains a major cardiovascular risk factor requiring novel therapeutic strategies beyond conventional statin therapy. This study investigated the antihyperlipidemic and antioxidant properties of Ficus elastica Roxb. ex Hornem. (Moraceae) phytochemicals through integrated in vitro, in vivo , and in silico approaches. Experimental approach: Eight chromatographic subfractions were screened for 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitory activity. Lipid profile, lipid peroxidation, and histopathology were evaluated in rats fed a high-fat diet to induce hyperlipidemia. Chemical composition was characterized using liquid chromatography high-resolution mass spectrometry (LC-HRMS) and subsequently investigated through molecular docking simulations. Findings/Results: Subfraction 4 demonstrated the strongest HMG-CoA reductase inhibitory activity. In vivo evaluation in high-fat diet-induced hyperlipidemic rats revealed dose-dependent improvements in all lipid parameters, with effects statistically comparable to simvastatin. Subfraction 4 additionally reduced serum malondialdehyde to levels statistically indistinguishable from normal controls, indicating restoration of oxidative homeostasis. Histological preservation of aortic endothelial integrity and elastic fiber organization was associated with reduced intima-media thickness, suggesting attenuation of early atherosclerotic changes. LC-HRMS analysis tentatively identified four major constituents, including phlorin, clausarinol, ginsenoyne C, and piptolinic acid A. Molecular docking analysis suggested that clausarinol and ginsenoyne C exhibited comparatively higher predicted binding affinity than simvastatin toward PCSK9 and PPAR-α, respectively. Conclusion and implications: These findings support the potential of F. elastica phytochemicals as candidates for hyperlipidemia management.