convallatoxin and Colitis

Convallatoxin (CNT) is a cardiac glycoside isolated from Adonis amurensis Regel et Radde and has both anti-inflammatory and anti-proliferative properties. In the present study, the anti-inflammatory mechanisms of action of CNT was investigated in vitro and in vivo. Stimulation of mouse macrophages with lipopolysaccharide induced secretion of proinflammatory cytokines via suppression of peroxisome proliferator-activated receptor gamma (PPARγ) and activation of nuclear factor-κB (NF-κB), two transcription factors implicated in many inflammatory diseases. Notably, the effects of lipopolysaccharide were reversed by concomitant treatment of macrophages with CNT. Knockdown of PPARγ by siRNA inhibited the effect of convallatoxin on NF-κB activation. Because these transcription factors play a role in the development of ulcerative colitis in humans, the mice with experimental colitis induced by dextran sodium sulfate (DSS) was employed. Indeed, concomitant treatment with CNT ameliorated DSS-induced colitis symptoms, tissue damage, inflammatory cell infiltration, and proinflammatory cytokine production in the colon, and also reversed the activation of NF-κB and suppression of PPARγ. Collectively, these data indicate that CNT ameliorates colitic inflammation via activation of PPARγ and suppression of NF-κB, and suggest that CNT may be a promising treatment for inflammatory bowel disease (IBD).

Topics: Animals; Anti-Inflammatory Agents; Colitis; Colon; Cytokines; Dextran Sulfate; Female; Mice; Mice, Inbred C57BL; NF-kappa B; RAW 264.7 Cells; RNA, Small Interfering; Signal Transduction; Strophanthins