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Lancemaside A ameliorates colitis by inhibiting NF-κB activation in TNBS-induced colitis mice

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International Journal of Colorectal Disease Aims and scope Submit manuscript

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-κB activation of NF-κB 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-κB 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)-1β, tumor necrosis factor (TNF)-α, and IL-6, and their transcription factor, NF-κB, 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-1β, IL-6, and TNF-α 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-1β, IL-6, and TNF-α. Lancemaside A inhibited NF-κB activation induced by TNBS, as well as the expression of cyclooxygenase 2 and TLR-4. Lancemaside A also reduced the activity of intestinal bacterial β-glucuronidase that was induced by TNBS.

Conclusions

Lancemaside A ameliorates colitis via inhibition of TLR-4-linked NF-κB activation.

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Abbreviations

IBD:

inflammatory bowel disease

DMEM:

Dulbecco’s modified Eagle’s medium

ECL:

enhanced chemiluminescence

ELISA:

enzyme-linked immunosorbent assay

HA:

hemagglutinin

HEK:

human embryonic kidney

IL:

interleukin

LPS:

lipopolysaccharide

RIPA:

radio-immunoprecipitation assay

TLR:

toll-like receptor

TNBS:

2,4,6-trinitrobenzenesulfonic acid

TNF:

tumor necrosis factor

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Authors and Affiliations

  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

    Eun-Ha Joh, In-Ah Lee, Sang-Jun Han, SunJu Chae & Dong-Hyun Kim

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  1. Eun-Ha Joh
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  2. In-Ah Lee
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Correspondence to Dong-Hyun Kim.

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Joh, EH., Lee, IA., Han, SJ. et al. Lancemaside A ameliorates colitis by inhibiting NF-κB activation in TNBS-induced colitis mice. Int J Colorectal Dis 25, 545–551 (2010). https://doi.org/10.1007/s00384-009-0858-0

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