Lancemaside A ameliorates colitis by inhibiting NF-kappaB activation in TNBS-induced colitis mice.
OBJECTIVE
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-kappaB activation of NF-kappaB 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.


METHODS
We measured the ability of lancemaside A to inhibit LPS-stimulated, TLR-4-linked NF-kappaB 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)-1beta, tumor necrosis factor (TNF)-alpha, and IL-6, and their transcription factor, NF-kappaB, in intestinal mucosa by enzyme-linked immunosorbent assay and immunoblotting.


RESULTS
Intrarectal treatment of TNBS in mice caused colon shortening and also increased colonic expression of IL-1beta, 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-1beta, IL-6, and TNF-alpha. Lancemaside A inhibited NF-kappaB 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.


CONCLUSIONS
Lancemaside A ameliorates colitis via inhibition of TLR-4-linked NF-kappaB activation.
Joh
Eun-Ha
EH
Department of Life and Nanopharmaceutical Sciences and Department of Pharmaceutical Science, Kyung Hee University, 1, Hoegi, Dongdaemun-Ku, Seoul, 130-701, Republic of Korea.
Lee
In-Ah
IA
Han
Sang-Jun
SJ
Chae
Sunju
S
Kim
Dong-Hyun
DH
D000818:Animals; D002460:Cell Line; D003092:Colitis / Q000139:chemically induced / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D051546:Cyclooxygenase 2 / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D005243:Feces / Q000201:enzymology; D005966:Glucuronidase / Q000378:metabolism; D006801:Humans; D006820:Hyaluronic Acid / Q000378:metabolism; D018836:Inflammation Mediators / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism*; D012503:Saponins / Q000737:chemistry / Q000302:isolation & purification / Q000627:therapeutic use*; D051197:Toll-Like Receptor 4 / Q000378:metabolism; D014302:Trinitrobenzenesulfonic Acid
D016207:Cytokines; D018836:Inflammation Mediators; D008070:Lipopolysaccharides; D016328:NF-kappa B; D012503:Saponins; D051197:Toll-Like Receptor 4; C533150:lancemaside A; D014302:Trinitrobenzenesulfonic Acid; D006820:Hyaluronic Acid; C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2; D005966:Glucuronidase