The peptide semax affects the expression of genes related to the immune and vascular systems in rat brain focal ischemia: genome-wide transcriptional analysis

Abstract

BackgroundThe nootropic neuroprotective peptide Semax (Met-Glu-His-Phe-Pro-Gly-Pro) has proved efficient in the therapy of brain stroke; however, the molecular mechanisms underlying its action remain obscure. Our genome-wide study was designed to investigate the response of the transcriptome of ischemized rat brain cortex tissues to the action of Semax in vivo.ResultsThe gene-expression alteration caused by the action of the peptide Semax was compared with the gene expression of the “ischemia” group animals at 3 and 24 h after permanent middle cerebral artery occlusion (pMCAO). The peptide predominantly enhanced the expression of genes related to the immune system. Three hours after pMCAO, Semax influenced the expression of some genes that affect the activity of immune cells, and, 24 h after pMCAO, the action of Semax on the immune response increased considerably. The genes implicated in this response represented over 50% of the total number of genes that exhibited Semax-induced altered expression. Among the immune-response genes, the expression of which was modulated by Semax, genes that encode immunoglobulins and chemokines formed the most notable groups.In response to Semax administration, 24 genes related to the vascular system exhibited altered expression 3 h after pMCAO, whereas 12 genes were changed 24 h after pMCAO. These genes are associated with such processes as the development and migration of endothelial tissue, the migration of smooth muscle cells, hematopoiesis, and vasculogenesis.ConclusionsSemax affects several biological processes involved in the function of various systems. The immune response is the process most markedly affected by the drug. Semax altered the expression of genes that modulate the amount and mobility of immune cells and enhanced the expression of genes that encode chemokines and immunoglobulins. In conditions of rat brain focal ischemia, Semax influenced the expression of genes that promote the formation and functioning of the vascular system.The immunomodulating effect of the peptide discovered in our research and its impact on the vascular system during ischemia are likely to be the key mechanisms underlying the neuroprotective effects of the peptide.

The occurrence of putative cognitive enhancing research peptides in seized pharmaceutical preparations: An incentive for controlling agencies to prepare for future encounters of the kind

“…8 It has been shown that this heptapeptide has a cognition enhancing or nootropic action and positively influences the formation of memory and learning processes in rats. 7,9 A similar effect was also attributed to Semax, another synthetic heptapeptide, consisting of a fragment of adrenocorticotropic hormone (ACTH4-7)…”

“…Selank is a synthetic analog of the endogenous tuftsin peptide (a fragment of the human immunoglobulin G heavy chain) which was elongated at its C terminus by the addition of a tripeptide with the sequence PGP, in order to improve its metabolic stability . It has been shown that this heptapeptide has a cognition enhancing or nootropic action and positively influences the formation of memory and learning processes in rats . A similar effect was also attributed to Semax, another synthetic heptapeptide, consisting of a fragment of adrenocorticotropic hormone (ACTH4–7) C‐terminally fused to the tripeptide PGP.…”

“…A similar effect was also attributed to Semax, another synthetic heptapeptide, consisting of a fragment of adrenocorticotropic hormone (ACTH4–7) C‐terminally fused to the tripeptide PGP. Additionally, immunomodulatory and neuropsychotropic effects have also been ascribed to these molecules . Currently and to the best of our knowledge, no clinical studies with these peptides have been terminated or were given a positive advice by the European Medicines Agency.…”

“…6 Moreover, in 2018, another more hydrophobic unknown peptide was encountered in a seized sample, that, upon some mass spectral similarities (of the MS/MS spectrum) with Selank and subsequent de novo sequencing, followed by confirmation with a reference standard, confirmed the identity of this polypeptide, with the sequence MEHFPGP, as Semax. 7 Both these peptides are sold online and are probably taken to improve mental performance. Selank is a synthetic analog of the endogenous tuftsin peptide (a fragment of the human immunoglobulin G heavy chain) which was elongated at its C terminus by the addition of a tripeptide with the sequence PGP, in order to improve its metabolic stability.…”

“…Additionally, immunomodulatory and neuropsychotropic effects have also been ascribed to these molecules. 7,10,11 Currently and to the best of our knowledge, no clinical studies with these peptides have been terminated or were given a positive advice by the European Medicines Agency. Therefore, the use of these research peptides on humans has not been approved by the European Union and can therefore be considered illegal.…”