Dereplication of Natural Products from an Endophytic Fungus from Ocotea diospyrifolia with Anti-Inflammatory Potential Through Dual Modulation of PGE2 and LTB4 Release

Endophytic fungi are significant sources of structurally diverse natural products with promising pharmacological and biological applications. In this study, endophytic fungi isolated from Ocotea diospyrifolia leaves were investigated as potential producers of anti-inflammatory natural products using an integrated workflow combining biological screening, comparative metabolomics, and high-resolution mass spectrometry-based dereplication. Crude extracts from five endophytic fungi (designated as OD1, OD5, OD6, OD7, and OD8) were screened for their ability to inhibit prostaglandin E2 (PGE2) and leukotriene B4 (LTB4) release. Lentinus sp. OD5 extract displayed promising dual inhibitory activity, and its UHPLC-QTOF-HRMS-based metabolomic profiling enabled the annotation of two compounds. Mass spectrometry data analysis, combined with SIRIUS annotation, putatively identified rhodojaponin, a grayanane diterpene with reported anti-inflammatory activity, and tinocordiside, an immunomodulatory diterpenoid glycoside. These findings expand the chemical diversity currently associated with endophytic fungi and provide a strong foundation for the future isolation, structural confirmation, and pharmacological evaluation of anti-inflammatory metabolites with potential therapeutic applications.