Xiaoping Xu1, Lei Zhang1, Zhaohui Liu1, Yuan Pan1, Dong Chen1, Zhouyu Yang2, Qun Deng3, Xinghua Cao4, Y U Sun4, Zhijian Yang5, Robert M Hoffman6, Hong Yuan7. 1. Department of Anorectal Surgery, Yuhang District First People's Hospital, Hangzhou, Zhejiang Province, P.R. China. 2. Department of Anorectal Surgery, Changsha Traditional Chinese Medicine Hospital, Changsha, Hunan Province, P.R. China. 3. Department of Anorectal Surgery, Hangzhou Third People's Hospital, Hangzhou, Zhejiang Province, P.R. China. 4. Origin Biosciences Inc., Nanjing, Jiangsu Province, P.R. China. 5. Origin Biosciences Inc., Nanjing, Jiangsu Province, P.R. China AntiCancer Inc., San Diego, CA, U.S.A. 6. 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. 7. Department of Cardiology, Yuhang District First People's Hospital, Hangzhou, Zhejiang Province, P.R. China yuanhongy@163.com all@anticancer.com.
Abstract
BACKGROUND/AIM: 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. MATERIALS AND 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. CONCLUSION: Suppression of the TLR4/MyD88/NF-κB signaling pathway may be one of the mechanisms involved in the therapeutic efficacy of BSQW against UC.
BACKGROUND/AIM: 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. MATERIALS AND METHODS: The colitisrat 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. CONCLUSION: Suppression of the TLR4/MyD88/NF-κB signaling pathway may be one of the mechanisms involved in the therapeutic efficacy of BSQW against UC.