Cortagen is a synthetic tetrapeptide with the sequence Ala-Glu-Asp-Pro, abbreviated AEDP. It was designed by Vladimir Khavinson's group in St Petersburg from the amino acid analysis of Cortexin, a polypeptide preparation isolated from the cerebral cortex.

Is Cortagen an adrenal cortex peptide?

No. It is sometimes described that way, but the published literature describes it as derived from a brain cortex preparation, and we found no indexed study linking it to the adrenal gland.

What has Cortagen been shown to do?

In rats it was reported to speed regeneration of a cut sciatic nerve and to lower oxidative damage markers in the brain. In mice it changed the expression of about 1.5% of the transcripts measured in heart tissue. In cultured white blood cells from people aged 75 to 88 it loosened tightly packed chromatin. One study in chickens found no effect.

Has Cortagen been tested in human trials?

No controlled human trial appears in the indexed literature, and none is registered on ClinicalTrials.gov. Cortagen is not authorised as a medicine in the UK, EU or US.

Cortagen (Ala-Glu-Asp-Pro): What the Cerebral Cortex Bioregulator Research Shows

Quick Answer

Cortagen is the synthetic tetrapeptide Ala-Glu-Asp-Pro (AEDP), designed from the amino acid analysis of Cortexin, a peptide preparation from the cerebral cortex. Although it is sometimes labelled an adrenal peptide, its literature concerns the brain and nerves. The published work is small and mostly from the 2000s: nerve regeneration and oxidative stress studies in rats, gene expression in mice and chromatin changes in cultured human cells. No controlled human trial appears in the indexed literature.

Cortagen has one of the thinnest literatures among the well-known bioregulators: about fifteen records on PubMed at the time of writing, most of them short reports from the early 2000s. That makes it a clear example of how far a bioregulator's reputation can run ahead of its evidence. This article covers what Cortagen is, the proposed mechanism, what the studies report in which models, and how much the evidence can support.

What Cortagen is

Cortagen is a tetrapeptide of alanine, glutamic acid, aspartic acid and proline, written Ala-Glu-Asp-Pro or AEDP (molecular formula C17H26N4O9, molecular weight about 430.4 g/mol). According to its developers at the St Petersburg Institute of Bioregulation and Gerontology, it was obtained by directed synthesis based on the amino acid analysis of Cortexin, a polypeptide preparation isolated from the cerebral cortex. It differs from Epithalon (Ala-Glu-Asp-Gly) only in its final residue. Pinealon is described as coming from the same source preparation.

Cortagen is sometimes described as an adrenal cortex peptide. We found no indexed study linking it to the adrenal gland: the cortex in its published research is the cerebral cortex.

The proposed mechanism

Cortagen sits within the bioregulator hypothesis: a short peptide enters cells, reaches chromatin and influences which genes are expressed, with effects concentrated in the tissue its parent extract came from. The observations offered in support are these.

Tissue-specific growth (cell culture): in organotypic culture, Cortagen stimulated the growth of explants from rat brain cortex, the tissue its parent extract came from, while related peptides stimulated their own matching tissues.
Chromatin (human cells in culture): in lymphocytes from people aged 75 to 88, Cortagen and other short peptides activated ribosomal genes and loosened densely packed chromatin. A group at Tbilisi State University, which has previously co-published with Khavinson, reported similar chromatin effects in 2023.
Gene expression (mice): in mice treated with Cortagen, a microarray analysis of 15,247 heart transcripts found significant changes in 234 (about 1.5%), matching 110 known genes. Some changes were shared with Vilon, Epithalon and melatonin, and some were specific to Cortagen.

None of this shows a direct DNA interaction for Cortagen specifically. The chromatin and expression changes are consistent with the hypothesis, but they could arise by other routes, and no study has identified the molecular target.

What the studies show

Nerve regeneration (rats): after the sciatic nerve was cut and sutured, rats treated with Cortagen showed a 27% faster growth rate and 40% higher conduction velocity in the regenerating nerve fibres, and a follow-up reported a delayed effect on the recovery of nerve function. Both were brief reports with co-authors from the Pavlov Institute of Physiology and the bioregulation institute.
Oxidative stress (rats): Cortagen and Epithalon lowered lipid peroxidation products and oxidative modification of proteins, although measured antioxidant activity in serum and the cerebral cortex fell at the same time.
Brain ischaemia (rats): a separate pharmacology group (Zarubina and Shabanov), with no co-authors from the institute, reported that Cortexin and Cortagen sped the recovery of behaviour in rats with chronic brain ischaemia and prevented excess lipid peroxidation in brain tissue. The paper is in Russian.
A negative result (birds): in chickens whose pituitary gland was removed, either shortly after hatching or in old age, Epithalon reversed the resulting changes in red blood cells, immunity and haemostasis, while Cortagen, one residue different, had no effect on those measures.
Humans: the 2004 microarray paper states that Cortagen showed effects on peripheral nerve recovery after injury in humans, but we found no controlled human study in the indexed literature, and none is registered on ClinicalTrials.gov.

How strong is the evidence?

Thin. The literature is small, mostly short reports published between 2000 and 2008, and almost all of it comes from the St Petersburg network and its collaborators. The rat ischaemia work is the main exception, and it is available only in Russian. A study in birds that tested Cortagen alongside Epithalon found no effect for Cortagen. There is no controlled human trial in the indexed literature and no registered trial.

The mechanism rests on inference from chromatin and gene expression changes rather than direct evidence, and the nerve regeneration findings have not been followed up in the indexed literature for more than two decades. A fair reading is a set of early, mostly single-network animal and cell findings, not a characterised compound.

Where Cortagen fits

For how the bioregulators fit together, see our guide to bioregulator peptides and what the Khavinson research actually claims.

References

Anisimov SV, et al. (2004). "Elucidation of the effect of brain cortex tetrapeptide Cortagen on gene expression in mouse heart by microarray." Neuro Endocrinology Letters. PubMed 15159690
Khavinson VK. (2001). "Tissue-specific effects of peptides." Bulletin of Experimental Biology and Medicine. PubMed 11713572
Khavinson VKh, et al. (2004). "Effects of short peptides on lymphocyte chromatin in senile subjects." Bulletin of Experimental Biology and Medicine. PubMed 15085253
Lezhava T, et al. (2023). "Epigenetic modification under the influence of peptide bioregulators on the 'old' chromatin." Georgian Medical News. PubMed 37042594
Turchaninova LN, et al. (2000). "Effect of tetrapeptide cortagen on regeneration of sciatic nerve." Bulletin of Experimental Biology and Medicine. PubMed 11276314
Kolosova LI, et al. (2002). "The delayed effect of cortagen on the restoration of injured nerve function." Doklady Biological Sciences. PubMed 12134478
Kozina LS. (2007). "Effects of bioactive tetrapeptides on free-radical processes." Bulletin of Experimental Biology and Medicine. PubMed 18239817
Zarubina IV, Shabanov PD. (2011). "Cortexin and cortagen as correcting agents in functional and metabolic disorders in the brain in chronic ischemia." Eksperimental'naia i Klinicheskaia Farmakologiia (in Russian). PubMed 21476278
Kuznik BI, et al. (2008). "Effects of epithalon and cortagene on immunity and hemostasis in neonatally hypophysectomized chicken and old birds." Advances in Gerontology (in Russian). PubMed 19432169