In Vitro and In Silico Anti-Inflammatory Activities of Crude Extract and Phloroglucinol Derivatives from Mallotus oppositifolius (Geisler) Müll. Arg. (Euphorbiaceae)

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.