Synergistic lipase inhibition by Garcinia parvifolia metabolites: a

introductionThe rising prevalence of obesity and metabolic disorders has intensified the demand for sustainable, plant-based functional ingredients for weight management. Garcinia parvifolia, an underutilized tropical fruit native to Malaysian Borneo, represents a promising natural source of anti-obesity compounds.

objectivesThis study aimed to decipher the complex, ligand interactions responsible for pancreatic lipase inhibition in G. parvifolia using a multi-disciplinary metabolomics-driven approach.

methodsExtracts of varying polarities (70% ethanol, acetone, chloroform, and hexane) were analyzed using ¹H NMR-based metabolomics, in vitro p-nitrophenyl butyrate (p-NPB) lipase assays, and in silico molecular docking.

resultsThe results demonstrated that solvent polarity critically dictates chemical diversity, with the 70% ethanol extract yielding the highest metabolite abundance and the strongest lipase inhibitory activity (IC₅₀ = 85.3 µg/mL). Multivariate data analyses, including Principal Component Analysis (PCA) and Partial Least Squares (PLS), revealed that this bioactivity is not driven by a single isolated compound, but rather by a synergistic combination of polar phenolic and aromatic metabolites, alongside supportive amino and organic acids. Molecular docking validated the inhibitory potential of key annotated metabolites, demonstrating that compounds such as catechin, β-sitosterol, and β-caryophyllene interact with the enzyme via reversible hydrogen bonding, van der Waals forces, and hydrophobic interactions, exhibiting binding affinities of - 6.09, - 6.34, and - 5.19 kcal/mol, respectively.

conclusionThese findings establish G. parvifolia as a viable, sustainable, and multi-targeted plant-based alternative to synthetic fat blockers. Its integration into functional foods and anti-obesity nutraceutical formulations offers significant potential for advancing preventive and personalized nutrition.