Exploration of bioactive natural products from tropical plant genetic resources: from diversity to functional seeds.

Abstract

Natural products derived from higher plants continue to represent an important source of structurally diverse and biologically active molecules for drug discovery. In particular, tropical plant genetic resources provide a rich reservoir of unique secondary metabolites owing to their exceptional biodiversity. Through long-term collaborative studies conducted mainly in Southeast Asia, extensive collections of tropical plant materials were screened for diverse biological activities, leading to the discovery of numerous bioactive natural products. Early phytochemical studies on medicinal plants such as Eurycoma longifolia, a well-known traditional herbal medicine widely used in Malaysia and Indonesia, also contributed to the establishment of our research platform for tropical natural product discovery. This review summarizes representative studies on structurally unique compounds isolated from tropical plant resources and highlights their biological activities and mechanisms of action. Representative examples include ceramicines, limonoids from Chisocheton ceramicus with anti-lipid droplet accumulation activity, calofolic acids from Calophyllum scriblitifolium exhibiting vasorelaxant effects through PI3K-PKA signaling modulation, cassiarins, alkaloids from Cassia siamea with potent antimalarial activity, bisindole alkaloids from Leuconotis species inducing autophagy through AKT-mTOR pathway inhibition, cyclolinopeptides from flaxseed suppressing osteoclast differentiation via the c-Fos/RANK axis, celogentins, bicyclic peptides from Celosia argentea inhibiting tubulin polymerization, and mollugin derivatives from Rubia species targeting TLR4-mediated inflammatory signaling pathways. These studies demonstrate that tropical plant-derived natural products possess remarkable structural diversity and act on biologically relevant molecular targets. Furthermore, several cases illustrate the importance of mechanistic analysis and structural modification for the optimization of pharmacological activity. Collectively, this review highlights the significance of biodiversity-driven natural product exploration as a strategy for identifying functional seeds for future drug discovery.