文献类型：期刊文献

英文题名：Screening of an anti-inflammatory peptide from Hydrophis cyanocinctus and analysis of its activities and mechanism in DSS-induced acute colitis

作者：Zheng, Zengjie[1];Jiang, Hailong[2];Huang, Yan[2];Wang, Jie[2];Qiu, Lei[2];Hu, Zhenlin[2];Ma, Xingyuan[1];Lu, Yiming[2]

机构：[1]E China Univ Sci & Technol, State Key Lab Bioreactor Engn, Shanghai 200237, Peoples R China;[2]Second Mil Med Univ, Sch Pharm, Dept Biochem Pharm, Shanghai 200433, Peoples R China

年份：2016

卷号：6

外文期刊名：SCIENTIFIC REPORTS

收录：;WOS:【SCI-EXPANDED(收录号:WOS:000375422800001)】；

基金：This work was supported by the National Natural Science Foundation of China (NO. 81274162) and Innovation Program of Shanghai Municipal Education Commission (NO. 14ZZ077).

语种：英文

摘要：Snake has been used for centuries as a traditional Chinese medicine, especially for therapeutic treatment for inflammatory diseases; however, its mechanisms of action and active constituents remain controversial. In our study, a tumor necrosis factor receptor 1 (TNFR1) selective binding peptide, Hydrostatin-SN1 (H-SN1), which was screened from a Hydrophis cyanocinctus venom gland T7 phage display library, was shown to exhibit significant anti-inflammatory activity in vitro and in vivo. As a TNFR1 antagonist, it reduced cytotoxicity mediated by TNF-alpha in L929 fibroblasts and effectively inhibited the combination between TNF-alpha with TNFR1 in surface plasmon resonance analysis. H-SN1 was also shown to suppress TNFR1-associated signaling pathways as it minimized TNF-alpha-induced NF-kappa B and MAPK activation in HEK293 embryonic kidney and HT29 adenocarcinoma cell lines. We next determined the effect of H-SN1 in vivo using a murine model of acute colitis induced by dextran sodium sulfate, demonstrating that H-SN1 lowered the clinical parameters of acute colitis including the disease activity index and histologic scores. H-SN1 also inhibited TNF/TNFR1 downstream targets at both mRNA and protein levels. These results indicate that H-SN1 might represent a suitable candidate for use in the treatment of TNF-alpha-associated inflammatory diseases such as inflammatory bowel diseases.