Unveiling the phytochemical and pharmacological potential of Amomum tsao-ko alkaloids: a combined metabolomics, network pharmacology, and molecular docking study

Amomum tsao-ko is a well-known medicinal and edible plant, valued for its unique flavor and health-promoting properties. While its volatile oil components have been extensively studied, the diversity and functional potential of its alkaloid constituents remain largely unexplored. In this study, we employed a multi-omics approach to investigate the alkaloid metabolome of fresh and dried fruits from three A. tsao-ko accessions. Using UPLC-MS/MS, we identified 183 alkaloids, revealing that both genetic background and post-harvest drying significantly shape the metabolic profile. Network pharmacology analysis of 76 differential alkaloids predicted 455 protein targets, with key bioactive compounds such as akuammigine and tryptamine potentially converging on the PI3K-Akt signaling pathway, a central regulator of metabolism and cell survival. Molecular docking further predicted the strong binding affinities of these alkaloids to core targets including EGFR, AKT1, and PIK3CA. Integrative transcriptomic analysis linked the accumulation of akuammigine to the differential expression of strictosidine synthase (STR1), identifying it as a candidate gene requiring functional validation in its biosynthesis. This study provides the first comprehensive alkaloid profile of A. tsao-ko , highlighting its potential as a functional food ingredient with multi-target bioactive properties. Our findings offer a foundation for further research into the health benefits of A. tsao-ko and support its development as a value-added functional food resource.