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Int. J. Mol. Sci. 2016, 17(11), 1940; doi:10.3390/ijms17111940

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

1,†
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2,†
,
2,†
,
2
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2
,
2
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2
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3,* and 2,*
1
School of Pharmacy, Fujian University of Traditional Chinese Medicine, Fuzhou 350108, China
2
Department of Biochemical Pharmacy, School of Pharmacy, Second Military Medical University, Shanghai 200433, China
3
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, Molecular and Cellular Biology)
View Full-Text   |   Download PDF [4814 KB, uploaded 22 November 2016]   |  

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. 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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MDPI and ACS Style

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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