An Integrated Ethnopharmacology-Docking-Zebrafish Pipeline for Philippine Natural Products in Type 2 Diabetes and Metabolic Syndrome

Diabetes mellitus (DM) and metabolic syndrome (MetS) are rapidly emerging as major global public health challenges in the modern era, creating urgent demand for accessible and culturally relevant therapeutic strategies. Philippine ethnomedicine represents a rich source of bioactive natural products, with medicinal plants such as Momordica charantia, Lagerstroemia speciosa, Moringa oleifera, Syzygium cumini, Annona muricata, Psidium guajava, and Blumea balsamifera traditionally used for metabolic disorders. This review proposes an integrated translational pipeline that combines ethnopharmacological selection, molecular docking, in silico ADMET profiling, and zebrafish (Danio rerio) diabetes/metabolic syndrome models to accelerate the discovery of antidiabetic leads from Philippine natural products. The proposed pipeline sequentially combines: (1) ethnopharmacological selection of candidate Philippine plants; (2) virtual screening via molecular docking against key metabolic targets (including PTP1B, DPP-4, SGLT2, and FBPase); (3) in silico ADMET profiling to assess pharmacokinetic viability; and (4) high-throughput phenotypic validation using zebrafish models of diabetes and metabolic syndrome. The framework also incorporates drug rescue and combination strategies to minimize developmental attrition. The integration of computational docking with whole-organism zebrafish assays allows for the rapid prioritization of phytochemical candidates that demonstrate both favorable binding affinity and safety profiles early in the discovery phase. This dual-layer validation successfully bridges the gap between single-target in silico predictions and complex, systemic vertebrate physiology. By merging traditional knowledge with digital and in vivo screening approaches, this proposed pipeline provides a robust strategy for advancing Philippine natural products toward evidence-based therapeutics for DM and MetS. Translating Philippine medicinal plants into credible antidiabetic candidates remains constrained by challenges in botanical and phytochemical standardization, achievable systemic exposure and bioavailability, rigorous computational and experimental validation, and regulatory translation from preclinical findings to reproducible, safe, and clinically relevant products.