PLANT-DERIVED PANCREATIC LIPASE INHIBITORS: ETHNOPHARMACOLOGY, PHYTOCHEMISTRY, AND THERAPEUTIC POTENTIAL IN OBESITY

Obesity affects more than one billion people worldwide, imposing economic burdens projected to exceed $4 trillion annually by 2035. Pancreatic lipase inhibition represents a mechanistically distinct peripheral approach to obesity management; however, orlistat the sole FDA-approved inhibitor is constrained by severe gastrointestinal adverse effects (>90% incidence), modest efficacy (2.9% placebo-subtracted weight loss), and poor adherence (60-77% discontinuation). Phytochemical alternatives, derived from diverse traditional medicine systems, offer superior tolerability, multi-target mechanisms, and global accessibility. This comprehensive review integrates ethnopharmacological, chemical, and pharmacological perspectives on phytochemical pancreatic lipase inhibitors. Traditional systems Traditional Chinese Medicine, Ayurveda, Indonesian Jamu, Mediterranean herbalism, and beyond demonstrate botanical diversity empirically corroborated by modern validation. Major classes, including polyphenols (flavonoids, catechins, tannins), terpenoids, alkaloids, saponins, carotenoids, and bioactive peptides, exhibit IC₅₀ values from 0.048 μM (oolonghomobisflavan A) to >100 μM. Standouts include galloylated tea catechins, Ginkgo biloba biflavones, and Nelumbo nucifera quercetin derivatives. These agents extend beyond lipase inhibition, modulating α-glucosidase, enriching Akkermansia muciniphila in the gut microbiome, suppressing inflammation, and inhibiting adipogenesis. Their limited systemic absorption long considered a limitation optimizes gastrointestinal localization and safety. Phytochemical lipase inhibitors thus fuse ancestral wisdom with scientific rigor, warranting personalized nutrition strategies, advanced delivery systems, untapped biodiversity exploration, and rigorous clinical trials for integration with conventional therapies.