title: Addition of Berberine to 5-Aminosalicylic Acid for Treatment of Dextran Sulfate Sodium-Induced Chronic Colitis in C57BL/6 Mice.
abstract: Ulcerative colitis (UC) is a common chronic remitting disease but without satisfactory treatment. Alternative medicine berberine has received massive attention for its potential in UC treatment. Conventional therapies with the addition of berberine are becoming attractive as novel therapies in UC. In the present study, we investigated the preclinical activity of a conventional oral 5-aminosalicylic acid (5-ASA) therapy plus berberine in experimental colitis. A subclinical dose of 5-ASA (200 mg/kg/day) alone or 5-ASA plus berberine (20 mg/kg/day) was orally administered for 30 days to C57BL/6 mice with colitis induced by three cycles of 2% dextran sulfate sodium (DSS). The disease severity, inflammatory responses, drug accumulation and potential toxicity of colitis mice were examined. The results showed that comparing to 5-ASA alone, 5-ASA plus berberine more potently ameliorated DSS-induced disease severity, colon shortening, and colon histological injury. Further, the up-regulation in mRNA level of colonic TNF-α as well as NFκB and JAK2 phosphorylation caused by DSS were more pronouncedly reversed in animals treated with the combination therapy than those treated with 5-ASA alone. Moreover, the addition of berberine to 5-ASA more significantly inhibited lymphocyte TNF-α secretion of DSS mice than 5-ASA alone. In the meanwhile, no extra drug accumulation or potential toxicity to major organs of colitis mice was observed with this combination treatment. In summary, our studies provide preclinical rationale for the addition of berberine to 5-ASA as a promising therapeutic strategy in clinic by reducing dose of standard therapy.
authors.affiliation: Lab of Brain and Gut Research, Hong Kong Chinese Medicine Research Center, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong, China.
authors.forename: Yan-hong
authors.initials: YH
authors.lastname: Li
authors.affiliation: Lab of Brain and Gut Research, Hong Kong Chinese Medicine Research Center, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong, China.
authors.forename: Man
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Lab of Brain and Gut Research, Hong Kong Chinese Medicine Research Center, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong, China.
authors.forename: Hai-tao
authors.initials: HT
authors.lastname: Xiao
authors.affiliation: Lab of Brain and Gut Research, Hong Kong Chinese Medicine Research Center, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong, China.
authors.forename: Hai-bo
authors.initials: HB
authors.lastname: Fu
authors.affiliation: Lab of Brain and Gut Research, Hong Kong Chinese Medicine Research Center, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong, China.
authors.forename: Alan
authors.initials: A
authors.lastname: Ho
authors.affiliation: Lab of Brain and Gut Research, Hong Kong Chinese Medicine Research Center, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong, China.
authors.forename: Cheng-yuan
authors.initials: CY
authors.lastname: Lin
authors.affiliation: School of Biomedical Sciences, Chinese University of Hong Kong, Hong Kong, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Huang
authors.affiliation: School of Biomedical Sciences, Chinese University of Hong Kong, Hong Kong, China.
authors.forename: Ge
authors.initials: G
authors.lastname: Lin
authors.affiliation: Lab of Brain and Gut Research, Hong Kong Chinese Medicine Research Center, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong, China.
authors.forename: Zhao-xiang
authors.initials: ZX
authors.lastname: Bian
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D001599:Berberine / Q000009:adverse effects / Q000627:therapeutic use*; D002478:Cells, Cultured; D003093:Colitis, Ulcerative / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D003106:Colon / Q000473:pathology; D016264:Dextran Sulfate / Q000009:adverse effects; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D053614:Janus Kinase 2 / Q000378:metabolism; D008297:Male; D019804:Mesalamine / Q000009:adverse effects / Q000627:therapeutic use*; D051379:Mice; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D001599:Berberine; D019804:Mesalamine; D016264:Dextran Sulfate; C507926:Jak2 protein, mouse; D053614:Janus Kinase 2