Pinealon

Pinealon (Glu-Asp-Arg) is a synthetic tripeptide bioregulator derived from the pineal gland, developed by Vladimir Khavinson at the Saint Petersburg Institute of Bioregulation and Gerontology as the cerebral cortex and pineal bioregulator. Pinealon is the smallest peptide in the CNS-targeting bioregulator series, alongside Cortagen (Ala-Glu-Asp-Pro) targeting the cortex, and Epithalon (Ala-Glu-Asp-Gly) targeting the pineal gland.

The tripeptide Glu-Asp-Arg (MW 390 Da) shares the Glu-Asp dipeptide core with both Epithalon (Ala-Glu-Asp-Gly) and Cortagen, suggesting this dipeptide unit may be the shared pharmacophore for CNS-targeting bioregulators. The distinguishing Arg at the C-terminus of Pinealon provides a positively charged residue that may facilitate interaction with negatively charged DNA or chromatin components in the proposed epigenetic mechanism.

Neuroprotection research has characterised Pinealon in neuronal cell death models: oxygen-glucose deprivation (OGD, modelling ischaemia), hydrogen peroxide-induced oxidative stress, glutamate excitotoxicity, and beta-amyloid peptide toxicity. Published Russian research has documented reductions in neuronal cell death markers (LDH release, caspase-3 activity) and improvements in mitochondrial membrane potential following Pinealon treatment in these models.

Circadian biology research connects Pinealon to melatonin synthesis regulation in pinealocyte models. Published data has examined AANAT (arylalkylamine N-acetyltransferase) mRNA and protein expression following Pinealon treatment, with proposed effects on melatonin production capacity. This places Pinealon research alongside Epithalon in the pineal function restoration research framework.

Gene expression research using Pinealon in aged versus young cortical neuron preparations has examined restoration of neurotrophic factor expression (BDNF, NGF, NT-3) and antioxidant enzyme expression (SOD1, GPX1) — endpoints connecting Pinealon to the broader neuroprotection and healthy ageing research landscape.

MW: 390.38 g/mol. Molecular formula: C13H22N6O7. Freely water-soluble. Reconstitute in bacteriostatic water at 1mg/mL. Store lyophilised at -20°C. For laboratory and analytical research purposes only.

Pinealon and circadian biology research: suprachiasmatic nucleus (SCN) slice preparations from adult rodents provide the primary model for circadian biology research. Prepare 400µm coronal hypothalamic slices containing bilateral SCN in ACSF (95% O2/5% CO2, 34°C). Record spontaneous neuronal firing by multi-electrode array (MEA) over 48-72 hours to characterise the circadian firing rhythm (peak activity during subjective day, trough at night). Apply Pinealon (1nM-1µM) during the subjective night and measure phase shift of subsequent firing rhythms — phase advances (earlier peak) or delays (later peak) quantify SCN chronobiological responsiveness to the bioregulator.

For AANAT expression research in pinealocyte models: rat pinealocytes can be isolated and maintained in culture under light-dark cycle conditions. Pinealon treatment (1-100nM) under dark-phase conditions (when AANAT is normally induced) allows assessment of whether the bioregulator modulates the light-dark transcriptional cycle of melatonin synthesis. Measure AANAT mRNA by RT-PCR at 3-hour intervals across the 12-hour dark phase, comparing Pinealon-treated versus vehicle-treated pinealocyte preparations. Compare with Epithalon (Ala-Glu-Asp-Gly) in parallel — both target the pineal/brain system but differ at the fourth residue (Gly vs Arg). Any difference in AANAT regulation between the two bioregulators at matched concentrations isolates the contribution of the C-terminal residue to pineal pharmacology. MW: 390.38 g/mol. Reconstitute in bacteriostatic water at 1mg/mL. Store lyophilised at -20°C. For laboratory and analytical research purposes only.

Pinealon and neuronal ageing research: replicative senescence in primary neuronal cultures can be modelled using prolonged passage of cortical astrocytes alongside neurons, or by using neurons from aged donors. Beta-galactosidase activity at pH 6.0 (senescence-associated beta-galactosidase, SA-beta-gal) serves as the primary senescence marker, quantified by X-gal staining and colorimetric assay. p21 and p16 expression by Western blot and RT-PCR provide additional senescence confirmation. Pinealon treatment (1nM-1µM) during or after senescence induction allows assessment of whether the tripeptide bioregulator modulates senescence marker expression — a research question directly aligned with the Khavinson bioregulator longevity hypothesis. Comparison with FOXO4-DRI (apoptosis of senescent cells) and SS-31 (mitochondrial protection) in parallel experiments characterises mechanistic complementarity: FOXO4-DRI clears senescent cells, SS-31 protects mitochondrial function, and Pinealon potentially modulates the epigenetic state of ageing neurons — three distinct mechanistic approaches to neuronal ageing biology that can be combined in factorial research designs. MW: 390.38 g/mol. Reconstitute in bacteriostatic water at 1mg/mL. Store lyophilised at -20°C. For laboratory and analytical research purposes only.