Quick summary
Cortistatin is a somatostatin-family neuropeptide with broader anti-inflammatory action via GHSR1a and MrgX2. It dramatically reduces colitis inflammation and prevents joint destruction in arthritis models.
Overview
Cortistatin is a neuropeptide belonging to the somatostatin family, existing in three biologically active isoforms: CST-14, CST-17, and CST-29. It shares 11 of 14 amino acids with somatostatin-14 yet is encoded by a separate gene. Cortistatin binds all five somatostatin receptors and additionally activates the ghrelin receptor (GHSR1a) and MrgX2. It exerts potent anti-inflammatory effects in experimental colitis, arthritis, and sepsis models, distinguishing it from somatostatin by its broader receptor profile and immunomodulatory potency.
Mechanism of action
Cortistatin's anti-inflammatory actions are mediated through multiple converging pathways. Binding to somatostatin receptors (particularly SSTR2/3/5) suppresses cAMP, reducing inflammatory cytokine production (TNF-α, IL-1β, IL-6, IL-12, IFN-γ, IL-17). Activation of GHSR1a on macrophages and dendritic cells shifts cytokine balance toward anti-inflammatory profiles. Cortistatin also inhibits NF-κB activation, reduces leukocyte migration, and promotes regulatory T-cell differentiation. In arthritis models, it directly binds TNF-α receptors and protects cartilage from destruction. Central actions include modulation of slow-wave sleep and suppression of growth hormone secretion.
Dosing protocols
| Purpose | Route | Dosage | Frequency | Notes |
|---|---|---|---|---|
| anti-inflammatory research (animal colitis/arthritis models) | intravenous | 0.1–1 nmol | once or twice daily per protocol | |
| peripheral immunomodulation (animal) | subcutaneous | 10–100 mcg/kg | daily for duration of experiment |
Dosing information is for educational purposes only. Consult a qualified healthcare professional before using any peptide.
Research summary
Preclinical evidence for cortistatin as an anti-inflammatory agent is robust. In experimental colitis models, cortistatin treatment dramatically reduced colonic inflammation, pro-inflammatory cytokine expression, and mucosal damage, improving survival. In collagen-induced arthritis, treatment completely abrogated joint swelling and cartilage/bone destruction. Cortistatin also reduces pain hypersensitivity in arthritis models through mechanisms independent of its anti-inflammatory action. A 2021 Nature Communications study reported structure-based design of a cortistatin analog with improved metabolic stability and efficacy in IBD models. Clinical translation is limited by cortistatin's short plasma half-life.[1][2][3][4]
Evidence grading
Each claimed benefit is graded by the strength of available evidence. Grades reflect study quality, not effect size.
Strong = multiple RCTs · Moderate = limited trials or observational · Preliminary = animal or in vitro only · Insufficient = anecdotal or no published data
Side effects
Side effects vary by individual. This is not an exhaustive list. Report unusual symptoms to a healthcare professional.
Common stacks
Peptides commonly paired with Cortistatin for synergistic effects.
Legal status
Cortistatin is a research peptide with no approved clinical applications. Somatostatin analogs (octreotide, lanreotide) are approved drugs but act through partially overlapping but distinct mechanisms.
Sourcing & access
Research compound
Cortistatin is classified as a research compound. Regulatory status varies by jurisdiction. Always verify current legal status and source from vendors providing third-party certificates of analysis (COA).
Frequently asked questions
Cortistatin is a neuropeptide in the somatostatin family existing as CST-14, CST-17, and CST-29. It shares 11 of 14 amino acids with somatostatin-14 but is encoded by a separate gene. It binds all five somatostatin receptors and additionally activates the ghrelin receptor and MrgX2, giving it broader immunomodulatory properties.
Cortistatin suppresses pro-inflammatory cytokines (TNF-alpha, IL-1beta, IL-6, IL-17) via somatostatin receptors, shifts macrophage cytokine balance toward anti-inflammatory profiles via GHSR1a, inhibits NF-kB activation, reduces leukocyte migration, and promotes regulatory T-cell differentiation. It also modulates slow-wave sleep and suppresses growth hormone.
Cortistatin is a research peptide with potential side effects including hypoglycemia from somatostatin receptor activation, GI motility reduction, and growth hormone suppression with repeated dosing. Its short plasma half-life of less than 10 minutes limits clinical translation.
Cortistatin has shown dramatic efficacy in preclinical models of colitis (reducing mucosal damage and improving survival), rheumatoid arthritis (completely abrogating joint swelling and cartilage/bone destruction), and sepsis. A 2021 Nature Communications study reported improved analogs with better metabolic stability for IBD treatment.