Discovery of anti-inflammatory compounds from the stem bark of Garcinia latissima through in vitro and in silico approaches.

Garcinia latissima Miq. has been traditionally used by local communities in Indonesia for wound healing and to relieve itching. A phytochemical investigation of the stem bark of G. latissima led to the isolation of 12 tocotrienol and triterpenoid derivatives, including two previously undescribed metabolites, δ-(E)-deoxy-amplexichromanoyl acetate (1) and (20S,24S)-20,24-epoxylanostane-3β,25-diol (2), whose structures were elucidated using HRESIMS and NMR spectroscopic analyses. Among the isolates, (20R)-eupha-8,25-diene-3β,24ξ-diol (11) suppressed nitric oxide production in LPS-stimulated RAW 264.7 cells by more than 60% at concentrations of 10 and 50 µM, without significant cytotoxicity (cell viability > 80%). It also reduced the release of several inflammatory mediators, particularly MCP-1, as determined by a membrane antibody array. ELISA confirmed a significant decrease in MCP-1 levels, up to 2.3- and 2.8-fold at 3 and 24 h, respectively, following pre-treatment with compound 11 at 50 µM. Molecular docking and molecular dynamics simulations indicated a strong binding affinity of compound 11 to MD2, TAK1, and NF-κB1, key proteins in the TLR-4 signaling pathway, with predicted affinities higher than those of reference ligands. ADMET analysis further suggested favorable drug-like properties, including high predicted oral bioavailability and minimal toxicity. These findings suggest that compound 11 has promising anti-inflammatory potential, warranting further experimental studies to elucidate its mechanism of action and to validate its effects in additional inflammation-related bioassays.