Xue Song1, Jing Li2, Yan Wang3, Changmin Zhou3, Zhichao Zhang3, Mengdi Shen3, Ping Xiang4, Xiaofeng Zhang1, Hao Zhao4, Liang Yu4, Lugen Zuo5, Jianguo Hu6. 1. Department of Central Laboratory, First Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui, China; Anhui Key Laboratory of Tissue Transplantation, Bengbu Medical College, Bengbu, China. 2. Anhui Key Laboratory of Tissue Transplantation, Bengbu Medical College, Bengbu, China; Department of Clinical Laboratory, First Affiliated Hospital of Bengbu Medical College, Bengbu, China. 3. Anhui Key Laboratory of Tissue Transplantation, Bengbu Medical College, Bengbu, China; Department of Clinical Medicine, Bengbu Medical College, Bengbu, China. 4. Department of Central Laboratory, First Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui, China. 5. Anhui Key Laboratory of Tissue Transplantation, Bengbu Medical College, Bengbu, China; Department of Gastrointestinal Surgery, First Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui, China. 6. Anhui Key Laboratory of Tissue Transplantation, Bengbu Medical College, Bengbu, China; Department of Clinical Laboratory, First Affiliated Hospital of Bengbu Medical College, Bengbu, China. Electronic address: jghu9200@163.com.
Abstract
OBJECTIVES: Clematichinenoside AR (AR) is a saponin extracted for traditional Chinese medicine with the effects of improving the expression of tight junction (TJ) proteins and mediating anti-inflammatory activities. However, its effect on Crohn's disease (CD) is still unknown. We aimed to investigate the impact of AR on CD-like colitis and determine the mechanism underlying its effects. METHODS: Interleukin-10 gene knockout (Il-10-/-) mice (male, fifteen weeks old) with spontaneous colitis were allocated to the positive control and AR-treated (32 mg/kg AR administered every other day by gavage for 4 weeks) groups. Wild-type (WT) mice (male, fifteen weeks old) composed the negative control group. The effects of AR on intestinal barrier function and structure and T cell responses as well as the potential mechanisms underlying these effects were investigated. RESULTS: AR treatment significantly improved spontaneous colitis in Il-10-/- mice as demonstrated by reductions in the inflammatory score, disease activity index (DAI) and levels of inflammatory factors. The effects of AR on colitis in Il-10-/- mice were related to protecting intestinal barrier function and maintaining immune system homeostasis (regulatory T cell (Treg)/T helper 17 (Th17) cell balance). The anticolitis effect of AR may partly act by downregulating PI3K/Akt signaling. CONCLUSIONS: AR may have therapeutic potential for treating CD in humans.
OBJECTIVES:ClematichinenosideAR (AR) is a saponin extracted for traditional Chinese medicine with the effects of improving the expression of tight junction (TJ) proteins and mediating anti-inflammatory activities. However, its effect on Crohn's disease (CD) is still unknown. We aimed to investigate the impact of AR on CD-like colitis and determine the mechanism underlying its effects. METHODS:Interleukin-10 gene knockout (Il-10-/-) mice (male, fifteen weeks old) with spontaneous colitis were allocated to the positive control and AR-treated (32 mg/kg AR administered every other day by gavage for 4 weeks) groups. Wild-type (WT) mice (male, fifteen weeks old) composed the negative control group. The effects of AR on intestinal barrier function and structure and T cell responses as well as the potential mechanisms underlying these effects were investigated. RESULTS:AR treatment significantly improved spontaneous colitis in Il-10-/- mice as demonstrated by reductions in the inflammatory score, disease activity index (DAI) and levels of inflammatory factors. The effects of AR on colitis in Il-10-/- mice were related to protecting intestinal barrier function and maintaining immune system homeostasis (regulatory T cell (Treg)/T helper 17 (Th17) cell balance). The anticolitis effect of AR may partly act by downregulating PI3K/Akt signaling. CONCLUSIONS:AR may have therapeutic potential for treating CD in humans.