Therapeutic Efficacy of the Traditional Chinese Medicine Baishaoqiwu on TNBS-induced Colitis is Associated with Down-regulation of the TLR4/MyD88/NF-κB Signaling Pathway.
OBJECTIVE
The traditional Chinese medicine Baishaoqiwu (BSQW) has been previously used to clinically treat inflammatory bowel diseases. However, the mechanisms of it's therapeutic efficacy remain unclear. The aim of this study was to examine the efficacy of BSQW on ulcerative colitis (UC) and the TLR4/MyD88/NF-κB signaling pathway in a rat model of colitis.


METHODS
The colitis rat model was induced by anal instillation of 2,4,6-trinitrobenzene sulfonic acid (TNBS). The animals with induced colitis were treated with BSQW at a dose of 13.2 mg/kg daily, p.o. Mesalazin was used as a positive control and was given to the animals with induced colitis at a dose of 420 mg/kg daily, p.o. The untreated animals with induced colitis and normal animals served as model controls and normal controls, respectively. Macroscopic and histological assessments were performed after treatment. The expression of MyD88, NF-κB P65 and TLR4 were determined by immunohistochemical analysis.


RESULTS
Administration of BSQW or Mesalazin ameliorated TNBS-induced macroscopic and histological damage in the rats with induced colitis. The macroscopic score and total colitis index were significantly reduced in the BSQW- and Mesalazin-treated groups compared to the model control group (p<0.05). BSQW or Mesalazin significantly inhibited TNBS-induced expression of the TLR4, MyD88 and NF-κB P65 genes. No treatment-related toxicity was found in either the BSQW- or the Mesalazin-treated groups.


CONCLUSIONS
Suppression of the TLR4/MyD88/NF-κB signaling pathway may be one of the mechanisms involved in the therapeutic efficacy of BSQW against UC.
Department of Anorectal Surgery, Yuhang District First People's Hospital, Hangzhou, Zhejiang Province, P.R. China.
Xiaoping
X
Xu
Department of Anorectal Surgery, Yuhang District First People's Hospital, Hangzhou, Zhejiang Province, P.R. China.
Lei
L
Zhang
Department of Anorectal Surgery, Yuhang District First People's Hospital, Hangzhou, Zhejiang Province, P.R. China.
Zhaohui
Z
Liu
Department of Anorectal Surgery, Yuhang District First People's Hospital, Hangzhou, Zhejiang Province, P.R. China.
Yuan
Y
Pan
Department of Anorectal Surgery, Yuhang District First People's Hospital, Hangzhou, Zhejiang Province, P.R. China.
Dong
D
Chen
Department of Anorectal Surgery, Changsha Traditional Chinese Medicine Hospital, Changsha, Hunan Province, P.R. China.
Zhouyu
Z
Yang
Department of Anorectal Surgery, Hangzhou Third People's Hospital, Hangzhou, Zhejiang Province, P.R. China.
Qun
Q
Deng
Origin Biosciences Inc., Nanjing, Jiangsu Province, P.R. China.
Xinghua
X
Cao
Origin Biosciences Inc., Nanjing, Jiangsu Province, P.R. China.
Y U
YU
Sun
Origin Biosciences Inc., Nanjing, Jiangsu Province, P.R. China AntiCancer Inc., San Diego, CA, U.S.A.
Zhijian
Z
Yang
AntiCancer Inc., San Diego, CA, U.S.A. Department of Surgery, University of California San Diego, San Diego, CA, U.S.A. yuanhongy@163.com all@anticancer.com.
Robert M
RM
Hoffman
Department of Cardiology, Yuhang District First People's Hospital, Hangzhou, Zhejiang Province, P.R. China yuanhongy@163.com all@anticancer.com.
Hong
H
Yuan
D000818:Animals; D003092:Colitis / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D003106:Colon / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D015536:Down-Regulation / Q000187:drug effects; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D007150:Immunohistochemistry; D008297:Male; D008516:Medicine, Chinese Traditional / Q000379:methods; D053594:Myeloid Differentiation Factor 88 / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism*; D008517:Phytotherapy; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects*; D051197:Toll-Like Receptor 4 / Q000378:metabolism*; D016896:Treatment Outcome; D014302:Trinitrobenzenesulfonic Acid
D004365:Drugs, Chinese Herbal; C507781:Myd88 protein, rat; D053594:Myeloid Differentiation Factor 88; D016328:NF-kappa B; D051197:Toll-Like Receptor 4; C000615791:baishaoqiwu; D014302:Trinitrobenzenesulfonic Acid
Baishaoqiwu; TLR4/MyD88/NF-κB signaling pathway; TNBS-induced colitis; therapy