Pinealon
Also known as: EDR peptide, Glu-Asp-Arg
Evidence: Preclinical
Overview
Khavinson-series synthetic tripeptide (EDR) from the brain drug Cortexin; protected neurons from oxidative stress in vitro and in rats, and preserved dendritic spines in Alzheimer model mice.
Pinealon (EDR, Glu-Asp-Arg) is a synthetic tripeptide that the developer describes as isolated from Cortexin, a brain cortex peptide drug (Khavinson 2020). It is not a pineal peptide; the pineal preparations in the family are Epitalon and Epithalamin. It cut ROS and necrotic death in rat cerebellar neurons and PC12 cells under oxidative stress (Khavinson 2011), improved learning in offspring of rats with prenatal hyperhomocysteinemia (Arutjunyan 2012), and at 400 mcg/kg intraperitoneally daily raised hippocampal spine density 11% in Alzheimer model mice (Khavinson 2021). Human reports are uncontrolled: 32 patients with organic brain syndrome (Meshchaninov 2015) and 72 with brain injury, cited only in a review.
Benefits
Lower ROS and necrotic death in neurons under oxidative stress (in vitro), better learning in offspring of hyperhomocysteinemic rats (rodent), dendritic spine preservation in Alzheimer model mice (rodent), small uncontrolled human reports (human, low quality)
Dosing reference
- Research dose
- 200 to 1000 mcg daily: vendor/community range, no published human dose. Mice received 400 mcg/kg intraperitoneally
- Range
- 200 to 1000 mcg, 1x daily
Sold as oral capsules and as lyophilized powder for injection. Mice received 400 mcg/kg intraperitoneally once daily for 2 months (Khavinson 2021). Human reports used oral dosing; doses are not given in the indexed abstracts (Khavinson 2020). Community protocols run 10 to 20 day courses two or three times a year; no study compared schedules.
Mechanism
Proposed. In cerebellar granule cells, neutrophils and PC12 cells it limited ROS accumulation dose-dependently, delayed ERK1/2 activation and altered the cell cycle; because cell-cycle effects continued above the doses that saturated ROS control, the authors propose a direct genomic action (Khavinson 2011). Docking places EDR binding sites in promoters of CASP3, GAP43, APOE, SOD2, PPARA and PPARG (Khavinson 2021). The developer's review links it to MAPK/ERK, caspase-3, p53, SOD2 and GPX1 (Khavinson 2020). Melatonin and circadian effects in the old text have no published source.
Evidence
Preclinical: animal or in vitro data only
- Dose-dependently limited ROS and necrotic death in cerebellar neurons, neutrophils and PC12 cells under oxidative stress (Khavinson et al., 2011)
- Given to pregnant rats with methionine-induced hyperhomocysteinemia, improved offspring learning and neuron resistance to oxidative stress (Arutjunyan et al., 2012)
- At 200 ng/mL, raised mushroom spines 71% in hippocampal neurons exposed to amyloid beta (Kraskovskaya et al., 2017)
- At 400 mcg/kg intraperitoneally daily for 2 months, raised CA1 spine density 11% in 5xFAD-M mice; LTP rescue was not significant (Khavinson et al., 2021)
- Human-trial status: no randomized trial. An uncontrolled study of 32 patients with organic brain syndrome reported biological-age changes and prooxidant activity (Meshchaninov et al., 2015)
References
- Pinealon increases cell viability by suppression of free radical levels and activating proliferative processes. Khavinson V, Ribakova Y, Kulebiakin K, Vladychenskaya E, et al., Rejuvenation Research, 2011
- Pinealon protects the rat offspring from prenatal hyperhomocysteinemia. Arutjunyan A, Kozina L, Stvolinskiy S, Bulygina Y, et al., International Journal of Clinical and Experimental Medicine, 2012
- Tripeptides Restore the Number of Neuronal Spines under Conditions of In Vitro Modeled Alzheimer's Disease. Kraskovskaya NA, Kukanova EO, Lin'kova NS, Popugaeva EA, et al., Bulletin of Experimental Biology and Medicine, 2017
- Neuroprotective Effects of Tripeptides-Epigenetic Regulators in Mouse Model of Alzheimer's Disease. Khavinson V, Ilina A, Kraskovskaya N, Linkova N, et al., Pharmaceuticals, 2021
- EDR Peptide: Possible Mechanism of Gene Expression and Protein Synthesis Regulation Involved in the Pathogenesis of Alzheimer's Disease. Khavinson V, Linkova N, Kozhevnikova E, Trofimova S, Molecules, 2020
- EFFECT OF SYNTHETIC PEPTIDES ON AGING OF PATIENTS WITH CHRONIC POLYMORBIDITY AND ORGANIC BRAIN SYNDROME OF THE CENTRAL NERVOUS SYSTEM IN REMISSION (in Russian). Meshchaninov VN, Tkachenko EL, Zharkov SV, Gavrilov IV, et al., Advances in Gerontology (Uspekhi Gerontologii), 2015
Side effects
No controlled safety study has been published in any species, and the animal and cell studies, almost all from the developing institute, were not designed to detect harm. An uncontrolled human study reported prooxidant activity by chemiluminescence and fewer circulating CD34+ cells (Meshchaninov 2015). Commonly reported (anecdotal): injection-site irritation with injectable forms; oral capsules draw few complaints.
Storage
- Storage
- Room temperature
- Lyophilized
- 24+ months
Pharmacology
- Half-life
- No published pharmacokinetic data in any species
- Bioavailability
- Not measured in any species; oral use reported in uncontrolled human studies (Khavinson 2020)
- Molecular weight
- 418.4 Da
- Sequence
- EDR (Glu-Asp-Arg)