In Vitro and In Silico Anti‐Inflammatory Activities of Crude Extract and Phloroglucinol Derivatives from <i>Mallotus oppositifolius</i> (Geisler) Müll. Arg. (Euphorbiaceae)

Abstract Numerous anti‐inflammatory agents are used nowadays to relieve daily aches and pain. However, their severe side effects often limit their therapeutic use. In this study, we investigate the anti‐inflammatory activity of the crude leaves extract of Mallotus oppositifolius and five of its phloroglucinol derivatives ( MO1 – MO5 ). From spectroscopic and spectrometric analysis, the compounds were identified as mallotojaponin B ( MO1 ), mallotojaponin D ( MO2 ), acronyculatin U ( MO3 ), acronyculatin T ( MO4 ), and mallotojaponin C ( MO5 ). A primary macrophage culture activated by Saccharomyces cereviseae (SC) was used to evaluate the anti‐inflammatory activity of the crude extract and isolated compounds which were found to be nontoxic to primary macrophages at concentrations ranging from 0.1–50 µg/mL. In addition, the tested samples inhibited the 5‐lipoxygenase activity, nitric oxide (NO), and tumor necrosis factor alpha (TNF‐α) production by viable primary mouse macrophages in a concentration‐dependent manner with MO1 and MO3 exhibiting the highest in vitro anti‐inflammatory activities. Moreover, in silico studies were performed with the isolated compounds to evaluate their binding capacities/scores against the main enzymes involved in inflammation mediation in human cells. The compounds showed good binding affinities to critical anti‐inflammation targets particularly mallotojaponin C ( MO5 ) (−44.55 Kcal/mol) and acronyculatin T ( MO4 ) (−41.44 Kcal/mol) which showed the highest affinity for 5‐lipoxygenase.