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Int. J. Mol. Sci. 2016, 17(11), 1940;

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

3,* and 2,*
School of Pharmacy, Fujian University of Traditional Chinese Medicine, Fuzhou 350108, China
Department of Biochemical Pharmacy, School of Pharmacy, Second Military Medical University, Shanghai 200433, China
Biomedical Research Center, Zhongshan Hospital, Fudan University, Shanghai 200032, China
These authors contributed equally to this work.
Authors to whom correspondence should be addressed.
Academic Editor: Charles J. Malemud
Received: 22 September 2016 / Revised: 31 October 2016 / Accepted: 14 November 2016 / Published: 22 November 2016
(This article belongs to the Section Biochemistry)
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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. View Full-Text
Keywords: H-TL1; Hydrophis cyanocinctus; anti-inflammatory; inflammatory bowel diseases; TNF-α H-TL1; Hydrophis cyanocinctus; anti-inflammatory; inflammatory bowel diseases; TNF-α

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Wang, N.; Huang, Y.; Li, A.; Jiang, H.; Wang, J.; Li, J.; Qiu, L.; Li, K.; Lu, Y. Hydrostatin-TL1, an Anti-Inflammatory Active Peptide from the Venom Gland of Hydrophis cyanocinctus in the South China Sea. Int. J. Mol. Sci. 2016, 17, 1940.

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