Sialorphin

Sialorphin is an NEP and APN inhibitor. It effectively prevents the degradation of Substance P and methionine enkephalin by NEP. Sialorphin exhibits various biological activities, such as analgesia, regulation of male rat sexual behavior, and reduction of colitis. Additionally, it shows mild toxicity against certain tumor cells. Sialorphin is applicable in research related to pain, inflammatory bowel diseases, and tumors.

Sialorphin (0-10 μM) inhibits the degradation of Substance P by rat renal cell membranes and spinal cord membranes, with IC 50 values of 1 μM and 0.39 μM, respectively. It exhibits cytotoxicity against PC3 human prostate cancer cells (LC 50 : 185 μM) at concentrations of 50-1000 μM over 48 hours, while no LC 50 is reached for LN18 human glioblastoma cells even up to 1000 μM, and shows no significant toxicity to A549, HCT116, and B16-F10 cells.

In male rats, sialorphin (50-100 μg/kg; intravenous injection; single dose) significantly reduces pain-related vocalizations and escape behaviors while increasing exploratory behaviors such as region crossing and rearing in an acupuncture pain model. In a formalin pain model, sialorphin (200 μg/kg; intravenous injection; single dose) markedly decreases paw licking time, thus inhibiting acute chemical nociceptive responses. Sialorphin (0.3-3 mg/kg; intraperitoneal injection; twice daily; 3-7 days) alleviates colitis in mice induced by TNBS, while sialorphin (1 mg/kg; intraperitoneal injection; twice daily; 7 days) shows no effect on DSS-induced colitis in mice. Additionally, sialorphin (0.3-3 µg/kg; intravenous injection; single administration) modulates sexual behavior in male rats in a dose-dependent manner.