Key papers ✓ 2✗ 2~ 1? 7

• ✓ Positive animalBull Exp Biol Med · 2000

  Effect of tetrapeptide cortagen on regeneration of sciatic nerve.

  Animalssize not reported10 days

  Animal study of intramuscular cortagen 10 µg/kg

  In rats with a cut and sutured sciatic nerve, 10 days of Cortagen injections increased nerve fibre growth rate by 27% and conduction velocity by 40%.

  Key resultCortagen increased growth rate and conduction velocity in regenerating nerve fibers by 27% and 40%, respectively.

  Study details

  Studied

  Rats after sciatic nerve transection and suturing

  Main outcome

  Growth rate and conduction velocity of regenerating nerve fibers

  Authors' conclusion

  Cortagen increased nerve regeneration speed and conduction velocity in transected rat sciatic nerves.

  Limitations

  Rat study; the abstract gives no group sizes, controls or statistics.

  PubMed 11276314
• ✓ Positive animalEksp Klin Farmakol · 2011

  [Cortexin and cortagen as correcting agents in functional and metabolic disorders in the brain in chronic ischemia].

  Animalssize not reported

  Animal study of cortexin and cortagen

  In rats with chronic brain ischemia, Cortagen (like the brain extract Cortexin) sped recovery of behavior and limited lipid peroxidation in brain tissue.

  Study details

  Studied

  Rats with chronic brain ischemia, with high and low resistance to hypoxia

  Main outcome

  Behavior recovery, lipid peroxidation and antioxidant activity in brain tissue

  Authors' conclusion

  Cortexin and cortagen accelerated behavioral recovery and prevented excessive lipid peroxidation and loss of antioxidant activity; the authors suggest they may increase neuroprotective therapy efficacy in chronic brain ischemia.

  Limitations

  Rat study; the abstract gives no numbers.

  PubMed 21476278
• ? Inconclusive animalBull Exp Biol Med · 2007

  Effects of bioactive tetrapeptides on free-radical processes.

  Animalssize not reported

  Animal study of injected epithalon and cortagen

  In rats, Epitalon and Cortagen injections lowered lipid peroxidation products and protein oxidation, alongside suppression of antioxidant activity in serum and cortex.

  Study details

  Studied

  Rats (serum and cerebral cortex)

  Main outcome

  Lipid peroxidation products, protein oxidation, antioxidant activity

  Authors' conclusion

  Epithalon and cortagen decreased lipid peroxidation products and oxidative modification of proteins in rats, accompanied by suppressed antioxidant activity in serum and cerebral cortex.

  Limitations

  Very brief abstract with no numbers; rat study.

  DOI 10.1007/s10517-007-0230-8PubMed 18239817
• ✗ Negative animalAdv Gerontol · 2008

  [Effects of epithalon and cortagene on immunity and hemostasis in neonatally hypophysectomized chicken and old birds].

  Animalssize not reported40 days

  Animal study of epithalon vs cortagene injections

  In hypophysectomized chickens and old birds, Cortagen did not affect anemia, immune deficiency or clotting changes, whereas Epitalon corrected them.

  Study details

  Studied

  Neonatally hypophysectomized chickens and old birds

  Compared with

  Epithalon (Ala-Glu-Asp-Gly) vs cortagene (Ala-Glu-Asp-Pro)

  Main outcome

  Erythrocytes, immunity and hemostasis

  Authors' conclusion

  Epithalon completely eliminated the shifts in erythrocytes, immunity and hemostasis, while cortagene did not affect the parameters studied.

  Limitations

  Bird study; no numbers in abstract. A null result for cortagene.

  PubMed 19432169
• ? Inconclusive animalNeuro Endocrinol Lett · 2004

  Elucidation of the effect of brain cortex tetrapeptide Cortagen on gene expression in mouse heart by microarray.

  Animalssize not reported5 consecutive days

  cDNA microarray gene expression analysis after cortagen injections

  Microarray study in mice: 5 days of Cortagen changed expression of 234 of 15,247 heart transcripts; the abstract also asserts, without data, a therapeutic effect on nerve recovery in humans.

  Key resultOf 15,247 transcripts analysed, 234 clones (1.53%) changed significantly, matching 110 known genes; maximum up- and down-regulation were +5.42 and -2.86.

  Study details

  Studied

  Female 6-month-old CBA mice (heart tissue)

  Compared with

  Control group; Vilon, Epitalon and melatonin profiles

  Main outcome

  Cardiac gene expression changes

  Authors' conclusion

  Cortagen produced both common and specific effects on cardiac gene expression compared with other short peptides and melatonin, providing clues to its mechanism of action.

  Limitations

  Mouse transcriptome screen; no functional outcomes or sample size in abstract.

  PubMed 15159690
• ? Inconclusive in vitroBull Exp Biol Med · 2004

  Effects of short peptides on lymphocyte chromatin in senile subjects.

  Cells / lab

  In vitro study of five short peptides (Vilon, Epithalon, Livagen, Prostamax, Cortagen) on chromatin

  In cultured white blood cells from people aged 75-88, Cortagen and other short peptides decondensed chromatin and activated ribosomal genes.

  Study details

  Studied

  Leukocytes from subjects aged 75-88 years

  Compared with

  Untreated cells

  Main outcome

  Ribosome gene activity and chromatin condensation

  Sample

  Number of subjects not stated; leukocytes from subjects aged 75-88

  Authors' conclusion

  All peptides activated ribosome genes and decondensed chromatin; Epithalon, Livagen and Prostamax decondensed chromosome 1 pericentromeric chromatin.

  Limitations

  In vitro; not specific to Prostamax; no clinical outcome.

  DOI 10.1023/b:bebm.0000024393.40560.05PubMed 15085253
• ? Inconclusive in vitroBull Exp Biol Med · 2002

  In vitro effect of short peptides on expression of interleukin-2 gene in splenocytes.

  Cells / lab

  In vitro comparison of Vilon, Epithalon and Cortagen

  Mouse splenocytes: cortagen activated interleukin-2 mRNA synthesis without inducers, but less strongly than Vilon and Epithalon; cell culture only.

  Study details

  Studied

  Splenocytes from CBA mice

  Main outcome

  Interleukin-2 mRNA synthesis

  Authors' conclusion

  All three peptides activated IL-2 mRNA synthesis in the absence of specific inducers; Vilon and Epithalon were most potent and Cortagen produced a less pronounced effect.

  Limitations

  Cell culture; no numbers or sample size in abstract.

  DOI 10.1023/a:1020210615148PubMed 12447482
• ✗ Negative in vitroBull Exp Biol Med · 2002

  Effects of short peptides on thymocyte blast transformation and signal transduction along the sphingomyelin pathway.

  Cells / lab

  In vitro comparison of Vilon, Epithalon and Cortagen

  Mouse thymocytes: cortagen had no comitogenic effect (unlike Vilon) and a weaker effect than Vilon and Epithalon on sphingomyelinase activity; cell culture only.

  Study details

  Studied

  Mouse thymocytes

  Main outcome

  Thymocyte proliferation and sphingomyelinase activity

  Authors' conclusion

  Vilon had the most potent comitogenic effect, Epithalon less so, and Cortagen produced no such effects; Vilon also stimulated sphingomyelinase more than the other two.

  Limitations

  Cell culture; no numbers in abstract. A null result for cortagen.

  DOI 10.1023/a:1019830308824PubMed 12420072
• ? Inconclusive animalBull Exp Biol Med · 2005

  Synthesis of IL-2 mRNA in cells of rat hypothalamic structures after injection of short peptides.

  Animalssize not reported

  Animal study of injected Vilon, Epithalon and Cortagen

  Rat brain sections: Vilon, Epithalon and Cortagen modulated IL-2 gene expression in cells of some hypothalamic structures, depending on timing and route of injection; no numbers given.

  Study details

  Studied

  Rats (hypothalamic sections analysed by in situ hybridization)

  Main outcome

  IL-2 mRNA in hypothalamic cells

  Authors' conclusion

  The three short synthetic peptides modulated IL-2 gene expression in cells of some hypothalamic structures depending on administration time and route.

  Limitations

  Very brief abstract; no numbers, groups or sample size.

  DOI 10.1007/s10517-005-0388-xPubMed 16224591
• ? Inconclusive animalBull Exp Biol Med · 2006

  Production of lymphocyte-activating factors by mouse macrophages during aging and under the effect of short peptides.

  Animalssize not reported

  Ex vivo study of Vilon, Epithalon and Cortagen on LPS-stimulated macrophages

  Mouse macrophages: young and old animals differed in production of lymphocyte-activating factors, and Vilon, Epithalon and Cortagen had opposite modulating effects in young vs old mice; ex vivo, no numbers.

  Study details

  Studied

  Peritoneal macrophages from young and old mice

  Main outcome

  Production of lymphocyte-activating factors

  Authors' conclusion

  Lymphocyte-activating factor production was lower in old animals and the short peptides had opposite modulating effects in young and old mice, a possible route to correcting immune ageing.

  Limitations

  Ex vivo mouse cells; no numbers; effects of cortagen alone not separated in abstract.

  DOI 10.1007/s10517-006-0366-yPubMed 17426849
• ? Inconclusive in vitroBull Exp Biol Med · 2001

  Tissue-specific effects of peptides.

  Cells / lab

  In vitro explant growth assay

  Rat tissue explants: Cortagen stimulated growth of brain-cortex explants (and Epithalon, Livagen, Vilon stimulated their matching tissues); organ culture only.

  Study details

  Studied

  Organotypic explant cultures from rat brain cortex, subcortical structures, liver and thymus

  Main outcome

  Explant growth

  Authors' conclusion

  The peptides stimulated growth of explants from the tissues whose peptide extracts were used for their design, i.e. tissue-specific effects; Cortagen acted on brain cortex.

  Limitations

  Tissue culture; no numbers in abstract; developer's institute.

  DOI 10.1023/a:1013058701974PubMed 11713572
• ~ Mixed animalRussian-languageОбзоры по клинической фармакологии и лекарственной терапии · 2013

  Нейронопротекторное действие кортексина и кортагена

  Animalssize not reported

  Electrophysiology; cortagen 0.1-10000 uM compared with Cortexin and glycine

  Mollusc neurons: cortagen at 0.1-100 uM hyperpolarized neurons by 2-3 mV and slowed spontaneous firing (more than cortexin), but at higher concentrations (10 mM) depolarized them and blocked sodium and calcium currents by 80-90%, which the authors call non-specific or toxic.

  Key resultCortagen 0.1-100 uM hyperpolarized neurons by 2-3 mV; at high concentration sodium and calcium currents were suppressed up to 80-90%.

  Study details

  Studied

  Identified neurons of mollusc pedal ganglia, recorded with microelectrodes, and isolated neurons under voltage clamp

  Main outcome

  Resting and action potentials, firing rate, ion currents

  Authors' conclusion

  Low concentrations of cortagen had an activating (neuroprotective) effect on neurons, stronger than Cortexin; at very high concentrations effects were non-specific and even toxic.

  Limitations

  Invertebrate neurons in vitro; no sample sizes in text; Russian-journal paper from a pharmacology research institute.

  CyberLeninka (Russian)

Reported side effects

No human safety data in the published literature.

✓ positive · ✗ negative · ~ mixed · ? inconclusive, judged on each paper's own main outcome. Grades: A strong human evidence → D little or none. Papers and verdicts are drawn from PubMed, Europe PMC and Russian journals (CyberLeninka); not medical advice.