Anti-Inflammatory Effect of 21α-Methylmelianol In Vitro and In Vivo via NF-κB/STAT Signaling Pathway Modulation

Melia azedarach L., also known as the chinaberry tree, has long been used in traditional medicine to treat inflammatory conditions. In this study, we preliminarily investigated the anti-inflammatory effect of 21α-methylmelianol (MMN), a tirucallane-type triterpenoid isolated from M. azedarach, in lipopolysaccharide (LPS)-mediated RAW264.7 macrophages in vitro and in a dextran sodium sulfate (DSS)-stimulated ulcerative murine colitis model in vivo. MMN reduced LPS-stimulated nitric oxide production without inducing cytotoxicity. It significantly attenuated LPS-induced protein expression of reactive oxygen species and effectively suppressed the production of pro-inflammatory factors, including tumor necrosis factor-alpha (TNF-α), interleukin (IL)-6, and IL-1β. In addition, mechanistic investigations showed that MMN inhibited signal transduction and activator of STAT3 phosphorylation and activation of nuclear factor κB (NF-κB). In mice with DSS-induced colitis, MMN attenuated DSS-mediated pathological manifestations, including colon shortening, body weight loss, and histopathological alterations. Its in vivo effects were associated with the regulation of pro- and anti-inflammatory cytokine levels through suppression of the NF-κB signaling cascade and downstream inflammatory pathways. Collectively, these findings provide compelling evidence of the anti-inflammatory properties of MMN and highlight its therapeutic potential for the management of inflammatory disorders.