Berberine ameliorates TNBS-induced colitis by inhibiting lipid peroxidation, enterobacterial growth and NF-κB activation.
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-α-phosphatidylcholine as well as TLR-4-linked NF-κB 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-1β, IL-6, and TNF-α, but increased IL-10 expression in the colons of TNBS-treated C3H/HeN and C3H/HeJ mice. Berberine also inhibited NF-κB 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-κB and weakly via MAPKs. Based on these findings, berberine may improve colitis by inhibiting lipid peroxidation, enterobacterial growth and NF-κB activation.
Lee
In-Ah
IA
Department of Life and Nanopharmaceutical Sciences, Kyung Hee University, 1, Hoegi, Dongdaemun-ku, Seoul 130-701, Republic of Korea.
Hyun
Yang-Jin
YJ
Kim
Dong-Hyun
DH
D000818:Animals; D001599:Berberine / Q000494:pharmacology* / Q000627:therapeutic use; D003092:Colitis / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism / Q000382:microbiology; D004755:Enterobacteriaceae / Q000187:drug effects* / Q000254:growth & development*; D004789:Enzyme Activation / Q000187:drug effects; D057809:HEK293 Cells; D006801:Humans; D007249:Inflammation / Q000139:chemically induced / Q000378:metabolism; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000187:drug effects / Q000201:enzymology / Q000382:microbiology; D015227:Lipid Peroxidation / Q000187:drug effects*; D008070:Lipopolysaccharides / Q000494:pharmacology; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000276:immunology; D008297:Male; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism*; D014302:Trinitrobenzenesulfonic Acid / Q000494:pharmacology*
D008070:Lipopolysaccharides; D016328:NF-kappa B; D001599:Berberine; D014302:Trinitrobenzenesulfonic Acid; D020928:Mitogen-Activated Protein Kinases