Fan Wu1, Qingqing Shao2, Meilin Hu3, Yan Zhao4, Ruolan Dong5, Ke Fang6, Lijun Xu7, Xin Zou8, Fuer Lu9, Jingbin Li10, Guang Chen11. 1. Institute of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China. Electronic address: 18202729109@163.com. 2. Institute of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China. Electronic address: 18202734254@163.com. 3. Department of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China. Electronic address: 497079049@qq.com. 4. Department of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China. Electronic address: johnsonchau@sina.com. 5. Department of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China. Electronic address: yanrong0727@tom.com. 6. Department of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China. Electronic address: 370440692@qq.com. 7. Institute of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China. Electronic address: 979883165@qq.com. 8. Institute of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China. Electronic address: zouxingqx@sina.com. 9. Institute of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China. Electronic address: felu@tjh.tjmu.edu.cn. 10. Department of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China. Electronic address: tjlaojing@163.com. 11. Department of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China. Electronic address: guangchen@tjh.tjmu.edu.cn.
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE: Wu-Mei-Wan (WMW), a classic traditional Chinese herb medicine, is one of the most important formulations to treat digestive diseases from ancient times to the present. Previous study showed that WMW has satisfactory curative effects on experimental colitis, which motivating the application of WMW on colitis-associated complications. AIM OF THE STUDY: Intestinal fibrosis is usually considered to be a common complication of inflammatory bowel disease (IBD), particularly Crohn's disease (CD). Currently, no effective preventive measures or medical therapies are available for that. This work was designed to evaluate the effect and related mechanism of WMW on chronic colitis-associated intestinal fibrosis mice model. MATERIALS AND METHODS: The chronic colitis-associated intestinal fibrosis mice model was established by weekly intrarectal injection of 2,4,6-trinitrobenzene sulfonic acid (TNBS). The mice survival rate, disease activity index (DAI), colon length and histological score were examined to assess the therapeutic effect of WMW. Masson's trichrome staining, hydroxyproline assay, immunohistochemical staining and western blot analysis were used to evaluate fibrosis level. Colon inflammation was determined by ELISA and immunofluorescence staining. Immunofluorescence staining was used to evaluate fibroblasts proliferation and epithelial to mesenchymal transition (EMT), and the expression of key molecules in fibrosis was analyzed by western blot. RESULTS: Here we showed that WMW alleviates chronic colitis with improved survival rate, DAI, colon length and histological score. WMW inhibited the progression of intestinal fibrosis, decreased the expression of various fibrosis markers, such as α-SMA, collagen I, MMP-9 and fibronectin. In addition, WMW treatment reduced cytokines IL-6 and IFN-γ, and downregulated proinflammatory NF-κBp65 and STAT3 signaling pathways. Importantly, administration of WMW led to the inhibition of colon fibroblast proliferation and EMT, which are important mediators during fibrosis. Several key profibrotic pathways, including TGF-β/Smad and Wnt/β-catenin pathways, were downregulated by WMW treatment. CONCLUSION: Our work demonstrated that WMW can prevent intestinal fibrosis and the mechanisms involved may be related to the inhibition of colon fibroblasts activation.
ETHNOPHARMACOLOGICAL RELEVANCE: Wu-Mei-Wan (WMW), a classic traditional Chinese herb medicine, is one of the most important formulations to treat digestive diseases from ancient times to the present. Previous study showed that WMW has satisfactory curative effects on experimental colitis, which motivating the application of WMW on colitis-associated complications. AIM OF THE STUDY: Intestinal fibrosis is usually considered to be a common complication of inflammatory bowel disease (IBD), particularly Crohn's disease (CD). Currently, no effective preventive measures or medical therapies are available for that. This work was designed to evaluate the effect and related mechanism of WMW on chronic colitis-associated intestinal fibrosismice model. MATERIALS AND METHODS: The chronic colitis-associated intestinal fibrosismice model was established by weekly intrarectal injection of 2,4,6-trinitrobenzene sulfonic acid (TNBS). The mice survival rate, disease activity index (DAI), colon length and histological score were examined to assess the therapeutic effect of WMW. Masson's trichrome staining, hydroxyproline assay, immunohistochemical staining and western blot analysis were used to evaluate fibrosis level. Colon inflammation was determined by ELISA and immunofluorescence staining. Immunofluorescence staining was used to evaluate fibroblasts proliferation and epithelial to mesenchymal transition (EMT), and the expression of key molecules in fibrosis was analyzed by western blot. RESULTS: Here we showed that WMW alleviates chronic colitis with improved survival rate, DAI, colon length and histological score. WMW inhibited the progression of intestinal fibrosis, decreased the expression of various fibrosis markers, such as α-SMA, collagen I, MMP-9 and fibronectin. In addition, WMW treatment reduced cytokines IL-6 and IFN-γ, and downregulated proinflammatory NF-κBp65 and STAT3 signaling pathways. Importantly, administration of WMW led to the inhibition of colon fibroblast proliferation and EMT, which are important mediators during fibrosis. Several key profibrotic pathways, including TGF-β/Smad and Wnt/β-catenin pathways, were downregulated by WMW treatment. CONCLUSION: Our work demonstrated that WMW can prevent intestinal fibrosis and the mechanisms involved may be related to the inhibition of colon fibroblasts activation.
Authors: Joseph Sleiman; Sara El Ouali; Taha Qazi; Benjamin Cohen; Scott R Steele; Mark E Baker; Florian Rieder Journal: Expert Rev Gastroenterol Hepatol Date: 2020-12-28 Impact factor: 3.869
Authors: Jia Wenxiu; Yang Mingyue; Han Fei; Luo Yuxin; Wu Mengyao; Li Chenyang; Song Jia; Zhang Hong; David Q Shih; Stephan R Targan; Zhang Xiaolan Journal: Mediators Inflamm Date: 2021-06-25 Impact factor: 4.711