Comparison of Anti-Inflammatory Activities of Structurally Similar Triterpenoids Isolated from Bitter Melon

Abstract

Momordica charantia L., or bitter melon, has been suggested to exhibit anti-inflammatory activity. In a previous study, three structurally similar triterpenes, namely 5β,19-epoxy-25-methoxycucurbita-6,23-diene-3β,19-diol (EMCD), 5β,19-epoxy-25-methoxycucurbita-6,23-dien-3β-ol (EMCO), and 5β,19-epoxy-19,25-dimethoxycucurbita-6,23-dien-3β-ol (EDMO), were isolated from bitter melon. EMCD has been shown to exhibit in vitro anti-inflammatory activity. In this study, the anti-inflammatory activities of EMCD, EMCO, and EDMO were compared. All three compounds were toxic to the RAW 264.7 macrophage cell line but not the FL83B cells. EMCD and EMCO inhibited tumor necrosis factor (TNF)-α-induced inducible nitric oxide synthase (iNOS) expression in FL83B cells, and the IC50 values were 19.8 and 25.7 μM, respectively. By contrast, EDMO did not effectively reduce iNOS expression. Furthermore, EMCD and EMCO suppressed other TNF-α-induced proinflammatory signals including the activation of inhibitor kappa B kinase complex, the phosphorylation of inhibitor of nuclear factor-κB, and the activation of c-Jun kinase. EMCD consistently exhibited a higher efficacy than did EMCO in these assays. Hence, the in vivo anti-inflammatory activity of EMCD was tested. EMCD clearly repressed 12- O-tetradecanoylphorbol-13-acetate (TPA)-induced ear edema in mice. In conclusion, differences in the functional group on carbon 19 do affect the anti-inflammatory activities of EMCD, EMCO, and EDMO. EMCD exhibited the highest anti-inflammatory activity among these molecules, and its in vivo anti-inflammatory activity was confirmed.