Deciphering organ-specific chemistry and bioactivities of Plumeria rubra L. via integrated metabolomics, biological evaluation, and molecular docking studies

Despite the extensive ethnomedicinal use of Plumeria rubra L. (Apocynaceae), organ-specific metabolic specialization and its link to pharmacological properties remain poorly understood. Using LC–HRMS/MS combined with GNPS molecular networking, 160 metabolites across 14 phytochemical classes were annotated, revealing clear organ-specific profiles via multivariate analyses (PCA, HCA, OPLS-DA) and KEGG pathway enrichment analyses. Flowers were dominated by flavonoids and phenylpropanoids, leaves by iridoids and triterpenes, and stems by lignans. KEGG pathway enrichment further highlighted differential activation of monoterpenoid, phenylpropanoid, and flavonoid biosynthesis pathways among organs. A panel of in vitro assays demonstrated strong antioxidant activities across all organs, particularly in flowers, whereas enzyme inhibition varied by organ, leaves showed the strongest AChE inhibition, stems exhibited higher BChE and α-amylase inhibition, and both leaves and flowers displayed potent anti-tyrosinase and α-glucosidase activity. Pearson's correlation analysis revealed strong positive relationships between total phenolic and flavonoid contents and antioxidant activities, while enzyme inhibitory properties were primarily associated with iridoid, lignan, and triterpene abundance, highlighting chemistry–bioactivity coherence. Metabolite–bioactivitycorrelation further identified key biomarkers, such as quercetin glycosides, caffeoylquinic acids, plumieride, liriodendrin, and arjunolic acid, as major drivers of the observed pharmacological effects. Molecular docking supported these findings, demonstrating that the iridoid allamancin and the lignan hydroxypinoresinol establish stable interactions with AChE, tyrosinase, and α-glucosidase, showing multi-target inhibitory potential. Overall, the integration of LC–MS-based metabolomics, statistical modeling, and bioactivity correlation elucidates a clear functional specialization among P. rubra organs, highlighting the species as a promising source of multifunctional phytochemicals with combined antioxidant, neuroprotective, dermatological, and antidiabetic relevance.