2. Academic Validation
  3. Hydrostatin-TL1, an Anti-Inflammatory Active Peptide from the Venom Gland of Hydrophis cyanocinctus in the South China Sea

Hydrostatin-TL1, an Anti-Inflammatory Active Peptide from the Venom Gland of Hydrophis cyanocinctus in the South China Sea

  • Int J Mol Sci. 2016 Nov 22;17(11):1940. doi: 10.3390/ijms17111940.
Ningyuan Wang 1,  Yan Huang 2,  An Li 3,  Hailong Jiang 4,  Jie Wang 5,  Jianzhong Li 6,  Lei Qiu 7,  Ka Li 8,  Yiming Lu 9
Affiliations

Affiliations

  • 1 School of Pharmacy, Fujian University of Traditional Chinese Medicine, Fuzhou 350108, China. wangningyuan1230@163.com.
  • 2 Department of Biochemical Pharmacy, School of Pharmacy, Second Military Medical University, Shanghai 200433, China. huangyantiger2005@163.com.
  • 3 Department of Biochemical Pharmacy, School of Pharmacy, Second Military Medical University, Shanghai 200433, China. ezioleon@foxmail.com.
  • 4 Department of Biochemical Pharmacy, School of Pharmacy, Second Military Medical University, Shanghai 200433, China. jhlong1986@163.com.
  • 5 Department of Biochemical Pharmacy, School of Pharmacy, Second Military Medical University, Shanghai 200433, China. wj890801@126.com.
  • 6 Department of Biochemical Pharmacy, School of Pharmacy, Second Military Medical University, Shanghai 200433, China. lijianzhong1234@hotmail.com.
  • 7 Department of Biochemical Pharmacy, School of Pharmacy, Second Military Medical University, Shanghai 200433, China. qlcong021@163.com.
  • 8 Biomedical Research Center, Zhongshan Hospital, Fudan University, Shanghai 200032, China. karllee75@hotmail.com.
  • 9 Department of Biochemical Pharmacy, School of Pharmacy, Second Military Medical University, Shanghai 200433, China. bluesluyi@sina.com.
PMID: 27879679 DOI: 10.3390/ijms17111940
Abstract

Tumor necrosis factor (TNF)-α is a pleiotropic cytokine with intense pro-inflammatory and immunomodulatory properties, and anti-TNF-α biologics are effective therapies for various inflammatory diseases such as inflammatory bowel disease (IBD) and sepsis. Snake venom, as a traditional Chinese medicine, has been used in the treatment of inflammatory diseases in China for centuries. In this research, we constructed a venom gland T7 phage display library of the sea snake Hydrophis cyanocinctus to screen bioactive compounds that antagonize TNF-α and identified a novel nine-amino-acid peptide, termed hydrostatin-TL1 (H-TL1). In enzyme-linked immunosorbent assay (ELISA) and surface plasmon resonance (SPR) analyses, H-TL1 inhibited the interaction between TNF-α and TNF Receptor 1 (TNFR1). Further, H-TL1 attenuated the cytotoxicity of TNF-α in L929 cells as determined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. H-TL1 also decreased the mRNA expression of TNF-α/TNFR1 downstream targets and suppressed the phosphorylation of well-characterized proteins of downstream signal transduction pathways in HEK-293 cells. In vivo data demonstrated that H-TL1 protects Animals against dextran sodium sulfate (DSS)-induced acute colitis and lipopolysaccharide (LPS)-induced acute shock. Given its significant anti-inflammatory activity in vitro and in vivo, H-TL1 is a potential peptide for the development of new agents to treat TNF-α-associated inflammatory diseases.

Keywords

H-TL1; Hydrophis cyanocinctus; TNF-α; anti-inflammatory; inflammatory bowel diseases.

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