Pinealon

Research summary

Pinealon is a synthetic tripeptide, Glu-Asp-Arg (EDR), from the short-peptide bioregulator program led by Vladimir Khavinson at the St. Petersburg Institute of Bioregulation and Gerontology. It has been studied in cell cultures and rodent models of oxidative stress, hypoxia and amyloid toxicity, where researchers measured cell survival, dendritic spines and gene expression. Peptides Only supplies Pinealon as a lyophilized compound for laboratory research only.

Also known as

Glu-Asp-Arg · EDR peptide · EDR tripeptide

Sequence

Glu-Asp-Arg

What is Pinealon?

Pinealon is the synthetic tripeptide Glu-Asp-Arg, usually abbreviated EDR in the literature¹. It belongs to a family of short peptides that Khavinson's group calls bioregulators. That program began with polypeptide extracts of animal organs, such as the pineal preparation epithalamin and the thymic preparation thymalin, and moved on to synthetic di- and tetrapeptides designed from the amino-acid composition of those extracts, each reported to act on a matching tissue². Its better-known relative is the tetrapeptide Epithalon.

Despite the name, most Pinealon studies look at nerve cells rather than the pineal gland: cerebellar granule neurons, cortical cell cultures, hippocampal neurons and neurons induced from human skin fibroblasts^1,3,4,5.

What the research has examined

In the first detailed cell study, Pinealon limited the accumulation of reactive oxygen species in rat cerebellar granule cells, neutrophils and PC12 cells exposed to oxidative stress, reduced necrotic cell death, delayed ERK1/2 activation and altered the cell cycle, all in a concentration-dependent way. Because the cell-cycle effects continued at concentrations above those where the antioxidant effects leveled off, the authors proposed that the peptide also acts on the genome¹.

In rats fed excess methionine during pregnancy to raise homocysteine, offspring of dams given Pinealon performed better in spatial orientation and learning tests, and their cerebellar neurons accumulated fewer reactive oxygen species⁶. In old rats exposed to acute hypoxia, researchers measured brain caspase-3 activity and serum interleukin-6 and TNF, and interpreted the Pinealon results as a return of neuroinflammatory markers toward reference levels⁷.

Several studies use models of amyloid synaptotoxicity. In cultured mouse hippocampal neurons exposed to amyloid, EDR restored the number of mushroom-type dendritic spines to normal levels⁴. In 5xFAD transgenic mice, EDR and a related tripeptide prevented dendritic spine loss⁸. In neurons induced from elderly donors' fibroblasts, EDR increased dendritic branching and reduced oxidative DNA damage, but did not change mitochondrial or lysosomal activity or levels of the senescence marker p16⁵.

Proposed mechanism

Khavinson's group proposes that EDR enters cells and binds histone proteins or nucleic acids, changing the activity of the MAPK/ERK pathway and the synthesis of proteins such as caspase-3, p53, SOD2, GPX1 and the PPAR transcription factors⁹. Much of the supporting evidence is computational: docking studies placed EDR at promoter sequences of genes including CASP3, APOE, SOD2 and PPARG⁸, and modeling ranked EDR among ultrashort peptides that could be carried into cells by the LAT1, LAT2 and PEPT1 transporters¹⁰. In aging cortical cell cultures, EDR was reported to increase serotonin expression, with docking used to propose a link to the tryptophan hydroxylase gene³. These are hypotheses that independent laboratories have not yet tested.

Limitations of the evidence

The Pinealon literature is small and comes almost entirely from Khavinson's institute and its St. Petersburg collaborators, often in Russian-language journals such as Advances in Gerontology. We found no independent replication in PubMed-indexed research.

Human data are limited to small Russian studies. In one, 32 people aged 41 to 83 with organic brain syndrome were assessed on biological-age indicators after Pinealon and a related peptide; the same report noted prooxidant activity and a fall in circulating CD34-positive cells, and the abstract does not describe randomization or blinding¹¹.

• Most results come from cell culture or rodents, with endpoints such as reactive oxygen species, spine counts and caspase activity.
• Mechanistic claims rest heavily on molecular docking rather than direct binding measurements.
• Pinealon is not approved as a medicine by the FDA or the European Medicines Agency.

Sourcing Pinealon for research

Pinealon sits in our bioregulators range and is also part of the Semax / Selank / Pinealon Set. Every lot is independently tested and ships from the USA with a lot-matched certificate of analysis showing HPLC purity and mass-spec identity, published in our certificate library.

Further reading

• Epitalon vs Pinealon: Comparing Two Khavinson Bioregulator Peptides
• Semax vs Selank: How the Research Compares