Hydrostatin-TL1 (H-TL1) is a nonapeptide that acts as a TNF-α antagonist. This compound can be isolated from the venom glands of the sea snake Hydrophis cyanocinctus. H-TL1 competitively inhibits the interaction between TNF-α and TNFR1, thus reducing TNF-α cytotoxicity and inflammatory responses. It is applicable for research into TNF-α-related inflammatory diseases such as rheumatoid arthritis, osteoporosis, and inflammatory bowel disease (IBD).

Hydrostatin-TL1 (1-1000 nM, 18-20 hours) inhibits TNF-α induced L929 cell death in a concentration-dependent manner. Additionally, Hydrostatin-TL1 (0.2-1.6 μM) significantly suppresses the phosphorylation of p38, ERK, JNK, and IκB proteins in the TNF-α induced NF-κB and MAPKs signaling pathways in HEK-293 cells. However, it does not inhibit the IL-1β induced phosphorylation of IκB in HEK-293 cells. Furthermore, Hydrostatin-TL1 (0.1-0.8 nM) decreases TNF-α mediated pro-inflammatory factor mRNA expression (IL-8, TNF-α, ICAM-1, and VCAM-1) in HEK-293 cells in a dose-dependent manner.

Hydrostatin-TL1 administered intraperitoneally at a dosage of 0.5-1 mg/kg once daily for 7-8 consecutive days exhibits significant anti-inflammatory effects in a DSS-induced acute colitis mouse model. Additionally, Hydrostatin-TL1, given at doses of 20-80 μg/kg at 1, 3, and 5 hours, dose-dependently decreases mortality rates in a mouse model of LPS-induced acute shock.