Unraveling the alkaloid diversity and pharmacological potential of Ocimum: Integrated UPLC-MS/MS, network pharmacology, and transcriptomic insights for functional food and drug discovery

Abstract

As a dual-purpose medicinal and edible plant, Ocimum species offer significant pharmacological potential through their alkaloid metabolites. This study comprehensively analyzed alkaloid profiles in 10 Ocimum accessions using ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS), integrated with network pharmacology, molecular docking, and transcriptome sequencing to elucidate key pharmacological targets, therapeutic potentials, and biosynthetic pathways. We identified 191 alkaloids categorized into eight classes, with phenolamine and plumerane alkaloids predominating. Differential metabolite analysis revealed pronounced genetic diversity in alkaloid composition across accessions. Network pharmacology identified 14 pharmacologically active alkaloids linked to 160 potential targets, where core targets were enriched in cancer and neurological disease pathways. Molecular docking validated the strongest binding affinities of N-p-coumaroyltyramine and N-cis-feruloyltyramine to key targets, associating them with Alzheimer's disease and cardiovascular disorders. Transcriptomic analysis highlighted the pivotal role of the 4-coumarate-CoA ligase (4CL) genes in regulating alkaloid biosynthesis. This work systematically deciphers the biosynthetic network and pharmacological mechanisms of Ocimum alkaloids for the first time, proposing two accessions G085 and G134 as prioritized resources for targeted drug development. These findings provide both theoretical and practical foundations for advancing Ocimum resource utilization, deepening molecular insights into alkaloid biosynthesis while demonstrating their potential as novel drug candidates to address global health challenges.