Cortistatin

Research-Grade

Cortistatin (CST) is a neuropeptide existing in two primary bioactive forms — cortistatin-17 and cortistatin-14 — that shares 11 of 14 amino acids with somatostatin-14, including the critical FWKT motif required for somatostatin receptor binding. Despite this structural similarity, cortistatin is encoded by a separate gene (CORT), has a distinct expression pattern concentrated in the cerebral cortex and hippocampus, and produces biological effects that diverge significantly from somatostatin. Most notably, cortistatin is a potent inducer of slow-wave sleep when administered intracerebroventricularly in rodents — an effect somatostatin does not produce — and it binds to the ghrelin receptor (GHS-R1a) and the MrgX2 receptor, providing unique pharmacological actions beyond the somatostatin receptor family. Cortistatin's anti-inflammatory properties have generated substantial research interest. In animal models of inflammatory bowel disease, rheumatoid arthritis, sepsis, and experimental autoimmune encephalomyelitis, cortistatin administration reduced disease severity, often outperforming somatostatin. It acts by suppressing inflammatory cytokine production (TNF-alpha, IL-6, IL-1beta), inhibiting Th1 and Th17 immune responses, promoting regulatory T-cell generation, and modulating macrophage activation. These anti-inflammatory effects appear to involve both somatostatin receptors and cortistatin-specific signaling through MrgX2. The peptide's dual sleep-promoting and anti-inflammatory profile has made it an intriguing candidate for conditions where inflammation and sleep disruption intersect, though development remains preclinical.