Journal
EUROPEAN JOURNAL OF PHARMACOLOGY
Volume 648, Issue 1-3, Pages 162-170Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.ejphar.2010.08.046
Keywords
Berberine; Lipid peroxidation; 2,4,6-Trinitrobenzene sulfonic acid; Lipopolysaccharide; TLR-4; NF-kappa B
Categories
Funding
- Ministry of Education, Science and Technology [R33-2008-000-10018-0]
- National Research Foundation of Korea [R33-2008-000-10018-0] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
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Berberine, which is a major constituent of the rhizome of Coptidis japonica (CJ), inhibits IL-8 production in colonic epithelial cells and improves 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis in mice. In our preliminary studies, berberine inhibited lipid peroxidation in liposomes prepared from L-alpha-phosphatidyl-choline as well as TLR-4-linked NF-kappa B activation in HEK cells. Therefore, to clarify its anticolitic mechanism, we examined the inhibitory effects of berberine in TNBS-induced colitic C3H/HeN and C3H/HeJ mice. Its oral administration inhibited macroscopic score, body weight gain, colon shortening, myeloperoxidase activity, and lipid peroxidation in the colons of TNBS-treated C3H/HeN and C3H/HeJ mice. Berberine inhibited colonic expression of iNOS, COX-2, IL-1 beta, IL-6, and TNF-alpha, but increased IL-10 expression in the colons of TNBS-treated C3H/HeN and C3H/HeJ mice. Berberine also inhibited NF-kappa B activation in TNBS-treated C3H/HeN and C3H/HeJ mice, and inhibited TLR-4 expression in C3H/HeN, but not C3H/HeJ, mice. Treating C3H/HeN and C3H/HeJ mice with berberine significantly reduced the number of Enterobacteriaceae induced by TNBS, but restored the number of Bifidobacteria reduced by TNBS. Furthermore, berberine potently inhibited LPS-induced inflammation in peritoneal macrophages mainly via NF-kappa B and weakly via MAPKs. Based on these findings, berberine may improve colitis by inhibiting lipid peroxidation, enterobacterial growth and NF-kappa B activation. (C) 2010 Elsevier B.V. All rights reserved.
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