Lancemaside A Ameliorates Colitis By Inhibiting Nf-Kappa B Activation In Tnbs-Induced Colitis Mice

In a preliminary study, we found that lancemaside A, which is a main constituent of Codonopsis lanceolata used as an herbal medicine for inflammatory diseases, potently inhibits lipopolysaccharide (LPS)-stimulated, TLR-4-linked NF-kappa B activation of NF-kappa B luciferase reporter gene-transfected 293-hTLR4-hemagglutinin (HA) cells. Therefore, we investigated its inhibitory effect in 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced colitis in mice.We measured the ability of lancemaside A to inhibit LPS-stimulated, TLR-4-linked NF-kappa B activation in human embryonic kidney (HEK) cells, as well as to inhibit colitis outcomes in TNBS-induced colitis in mice. We also measured levels of the inflammatory markers, interleukin (IL)-1 beta, tumor necrosis factor (TNF)-alpha, and IL-6, and their transcription factor, NF-kappa B, in intestinal mucosa by enzyme-linked immunosorbent assay and immunoblotting.Intrarectal treatment of TNBS in mice caused colon shortening and also increased colonic expression of IL-1 beta, IL-6, and TNF-alpha expression. Oral administration of lancemaside A (10 and 20 mg/kg), inhibited colon shortening and myeloperoxidase activity in TNBS-induced colitic mice and also decreased colonic expression of IL-1 beta, IL-6, and TNF-alpha. Lancemaside A inhibited NF-kappa B activation induced by TNBS, as well as the expression of cyclooxygenase 2 and TLR-4. Lancemaside A also reduced the activity of intestinal bacterial beta-glucuronidase that was induced by TNBS.Lancemaside A ameliorates colitis via inhibition of TLR-4-linked NF-kappa B activation.