Eun-Ha Joh1, In-Ah Lee, Sang-Jun Han, Sunju Chae, Dong-Hyun Kim. 1. Department of Life and Nanopharmaceutical Sciences and Department of Pharmaceutical Science, Kyung Hee University, 1, Hoegi, Dongdaemun-Ku, Seoul, 130-701, Republic of Korea.
Abstract
PURPOSE: 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. RESULT: 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.
PURPOSE: 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 humanembryonic 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. RESULT: 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 coliticmice 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.
Authors: H C Jung; L Eckmann; S K Yang; A Panja; J Fierer; E Morzycka-Wroblewska; M F Kagnoff Journal: J Clin Invest Date: 1995-01 Impact factor: 14.808
Authors: A Poltorak; X He; I Smirnova; M Y Liu; C Van Huffel; X Du; D Birdwell; E Alejos; M Silva; C Galanos; M Freudenberg; P Ricciardi-Castagnoli; B Layton; B Beutler Journal: Science Date: 1998-12-11 Impact factor: 47.728