Meliasanines A–L, tirucallane-type triterpenoids from Melia toosendan with anti-inflammatory properties via NF-κB signaling pathway

Meliasanines A–L, twelve previously unreported tirucallane-type triterpenoids, together with fifteen known ones, have been isolated from the stem bark of Melia toosendan. Their structures and absolute configurations were determined based on HRESIMS, and NMR, combined with calculated ECD and single-crystal X-ray diffraction analyses. Subsequently, all compounds except 10 were evaluated for their inhibitory effect on the production of nitric oxide induced by lipopolysaccharide in RAW264.7 macrophage cells. The results indicated that seven compounds (1, 13, 14, 16, 20, 22, and 23) exhibited significant NO inhibitory effects, with IC50 values ranging from 1.35 to 5.93 μM, which were more effective than the positive control indomethacin (IC50 = 13.18 μM). Moreover, the corresponding results of Western blot analysis revealed that meliasanine A (1) can significantly suppress the protein expression of inducible nitric oxide synthase and cyclooxygenase 2 in a concentration-dependent manner. The mechanism study suggested that meliasanine A exerts an anti-inflammatory effect via the nuclear factor-κB signaling pathway by suppressing phosphorylation of P65 and IκBα. Twelve undescribed tirucallane-type triterpenoids were isolated from the stem bark of Melia toosendan. The compound 1 showed a significant anti-inflammatory effect via NF-κB signaling pathway. [Display omitted] •Twelve undescribed tirucallane-type triterpenoids were isolated from M. toosendan.•The absolute configurations of 1 and 5 were elucidated by X-ray crystallographic.•Seven compounds exhibited significant NO inhibitory effects with IC50 1.35–5.93 μM.•Meliasanine A exerts an anti-inflammatory effect via NF-κB signaling pathway.