Noordin_2026_Metabolomics_22_

INTRODUCTION: The 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. OBJECTIVES: This study aimed to decipher the complex, ligand interactions responsible for pancreatic lipase inhibition in G. parvifolia using a multi-disciplinary metabolomics-driven approach. METHODS: Extracts of varying polarities (70% ethanol, acetone, chloroform, and hexane) were analyzed using H NMR-based metabolomics, in vitro p-nitrophenyl butyrate (p-NPB) lipase assays, and in silico molecular docking. RESULTS: The 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 microg/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, beta-sitosterol, and beta-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. CONCLUSION: These 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.