Meliasanines A–L, Novel Tirucallane-Type Triterpenoids from Melia Toosendan with Anti-Inflammatory Properties Via Nf-Κb Signaling Pathway

Abstract

Meliasanines A–L, twelve previously unreported tirucallane-type triterpenoids, together with fifteen known analogues, have been isolated from the stem bark of Melia toosendan. Their structures and absolute configurations were determined based on HRESIMS, NMR, combined with calculated electronic circular dichroism (ECD) and single-crystal X-ray diffraction analyses. Subsequently, all compounds except 10 were evaluated for their inhibitory effect on nitric oxide (NO) production induced by lipopolysaccharide (LPS) in RAW264.7 macrophage cells. The results showed 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 better 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 the enzymes inducible nitric oxide synthase (iNOS) and cyclooxygenase 2 (COX-2) in a concentration-dependent manner. Further investigated results showed that meliasanine A exerts anti-inflammatory effect via the nuclear factor-κB (NF-κB) signaling pathway by inhibiting nuclear translocation of nuclear factor-κB phosphorylation (pIκBα).

Keywords: Melia toosendan, tirucallane-type triterpenoids, anti-inflammatory activity, NF-κB signaling pathway.