title: Screening of an anti-inflammatory peptide from Hydrophis cyanocinctus and analysis of its activities and mechanism in DSS-induced acute colitis.
abstract: 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-α in L929 fibroblasts and effectively inhibited the combination between TNF-α with TNFR1 in surface plasmon resonance analysis. H-SN1 was also shown to suppress TNFR1-associated signaling pathways as it minimized TNF-α-induced NF-кB 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-α-associated inflammatory diseases such as inflammatory bowel diseases.
authors.affiliation: State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai 200237, China.
authors.forename: Zengjie
authors.initials: Z
authors.lastname: Zheng
authors.affiliation: Department of Biochemical Pharmacy, School of Pharmacy, Second Military Medical University, Shanghai 200433, China.
authors.forename: Hailong
authors.initials: H
authors.lastname: Jiang
authors.affiliation: Department of Biochemical Pharmacy, School of Pharmacy, Second Military Medical University, Shanghai 200433, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Department of Biochemical Pharmacy, School of Pharmacy, Second Military Medical University, Shanghai 200433, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Biochemical Pharmacy, School of Pharmacy, Second Military Medical University, Shanghai 200433, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Qiu
authors.affiliation: Department of Biochemical Pharmacy, School of Pharmacy, Second Military Medical University, Shanghai 200433, China.
authors.forename: Zhenlin
authors.initials: Z
authors.lastname: Hu
authors.affiliation: State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai 200237, China.
authors.forename: Xingyuan
authors.initials: X
authors.lastname: Ma
authors.affiliation: Department of Biochemical Pharmacy, School of Pharmacy, Second Military Medical University, Shanghai 200433, China.
authors.forename: Yiming
authors.initials: Y
authors.lastname: Lu
mesh_terms: D000208:Acute Disease; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D016923:Cell Death / Q000187:drug effects; D002460:Cell Line; D003092:Colitis / Q000139:chemically induced* / Q000188:drug therapy* / Q000473:pathology; D016264:Dextran Sulfate; D004353:Drug Evaluation, Preclinical; D004546:Elapid Venoms / Q000737:chemistry / Q000627:therapeutic use*; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D007249:Inflammation / Q000188:drug therapy / Q000473:pathology; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008807:Mice, Inbred BALB C; D062105:Molecular Docking Simulation; D016328:NF-kappa B / Q000378:metabolism; D009500:Neutralization Tests; D019151:Peptide Library; D010455:Peptides / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D011485:Protein Binding / Q000187:drug effects; D017433:Protein Structure, Secondary; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D004546:Elapid Venoms; D016328:NF-kappa B; D019151:Peptide Library; D010455:Peptides; D047888:Receptors, Tumor Necrosis Factor, Type I; D014409:Tumor Necrosis Factor-alpha; D016264:Dextran Sulfate