Comprehensive Investigation into the Antioxidant Phytochemicals and Molecular Mechanisms of the Genus Ottelia: An Integrated Metabolomic and Network Pharmacology Approach

As endemic or regionally distinctive taxa in China, Ottelia species exhibit notable ecological adaptability as well as potential nutritional and medicinal value. Nevertheless, a comprehensive characterization and comparative analysis of the chemical constituents across this genus remain lacking, particularly for O. acuminata var. jingxiensis, O. fengshanensis, and O. guanyangensis. This knowledge gap has hindered the systematic exploitation and value-added utilization of Ottelia resources. In the present study, five Ottelia taxa—O. acuminata, O. acuminata var. jingxiensis, O. fengshanensis, O. guanyangensis, and O. alismoides—were investigated. By integrating widely targeted metabolomics, network pharmacology, and in vitro experimental validation, we identified Rivularin, Tenaxin I, Sinensetin, 8-Methoxyapigenin, Chrysoeriol, Hispidulin, Genkwanin, 5,2′-Dihydroxy-7,8-dimethoxyflavone, Kumatakenin, and Pectolinarigenin as key antioxidant constituents in the Genus Ottelia. Network-based analyses further indicated that these compounds predominantly act on PTGS1/2 and AR, and may mediate antioxidant activity primarily through the PI3K–Akt signaling pathway and pathways associated with EGFR tyrosine kinase inhibitor resistance. Collectively, these findings provide a scientific basis for the further development, functional evaluation, and sustainable utilization of the Genus Ottelia.