Anti‐Inflammatory Effect of 21 <i>α</i> ‐Methylmelianol In Vitro and In Vivo via <scp>NF</scp> ‐ <i>κ</i> <scp>B</scp> / <scp>STAT</scp> Signaling Pathway Modulation

<i>Melia azedarach</i> 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 21<i>α</i>-methylmelianol (MMN), a tirucallane-type triterpenoid isolated from <i>M. azedarach</i>, 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-<i>α</i>), interleukin (IL)-6, and IL-1<i>β</i>. In addition, mechanistic investigations showed that MMN inhibited signal transduction and activator of STAT3 phosphorylation and activation of nuclear factor <i>κ</i>B (NF-<i>κ</i>B). 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-<i>κ</i>B 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.