Chemical and Pharmacological Potential of Ficus Elastica Fractions for Anti-Hyperlipidemia: An Integrative Analysis from Molecular Docking, 𝐼𝑛 𝑉𝑖𝑡𝑟𝑜, and 𝐼𝑛 𝑉𝑖𝑣𝑜 Studies

Ficus elastica has demonstrated potential in regulating blood lipid profiles, yet comprehensive research on its anti-hyperlipidemic fraction-specific activities remains limited. This study aimed to evaluate the anti-hyperlipidemic potential of F. elastica fractions, through an integrated computational and experimental approach. The research employed a multifaceted methodology that combined computational modeling with experimental validation. In vitro, spectrophotometric analysis evaluated HMG-CoA reductase inhibition, using pravastatin as the reference standard. Pre-clinical tests were conducted on hyperlipidemic mice induced by a daily high-fat diet with ۱% cholesterol, and ۱% cholic acid supplementation once weekly for ۱۲ weeks. Molecular docking predictions were performed using the Autodock Vina platform in PyRx software, targeting proteins including HMGR, MTP, LPL, PCSK۹, and NPC۱L۱. In vitro investigations revealed the aqueous fraction demonstrated the most potent HMG-CoA reductase inhibitory activity, with an IC۵۰ of ۱۰.۲۱±۰.۶۴۵ µg/mL, closely approximating pravastatin's performance (IC۵۰: ۲.۸۰±۰.۳۲۷ µg/mL), followed by n-hexane fraction (IC۵۰: ۵۳.۱۲±۱.۵۵۱ µg/mL), and ethyl acetate fraction (IC۵۰: ۹۸.۵۰±۱.۲۲۵ µg/mL). In vivo experiments revealed substantial reductions in total cholesterol (۱۸.۳-۳۴.۵%), triglycerides (۴۵.۶-۵۴.۱%), and LDL cholesterol (۱۶.۴۱-۳۹.۷۱%), accompanied by a notable increase in HDL cholesterol (۲.۹-۵.۱%) with a dose of ۰.۱۵ mg/gBW showed no statistical difference (p-value >۰.۰۵) compared to simvastatin (۰.۱۸ mg/۲۰۰gBW). Molecular docking analyses pinpointed ۹,۱۰-dihydro-۱۰-(۳,۴-dihydroxyphenyl)-pyrano(۲,۳-h)catechin-۸-one as the primary bioactive compound driving these therapeutic effects through strategic inhibition of HMGR, MTP, as well as PCSK۹ and regulation of lipoprotein lipase. The aqueous fraction exhibits significant anti-hyperlipidemic properties, comparable to conventional pharmaceuticals.

کلیدواژه ها:

Ficus elastica ، Anti-hyperlipidemia ، Polar fraction ، Flavonoids ، Molecular docking