Melatonin D5, a deuterium-labeled version of melatonin, is a hormone produced by the pineal gland, known for its role as a selective ATF-6 inhibitor that promotes apoptosis in human hepatoma cells via COX-2 downregulation. Additionally, it activates melatonin receptors and exhibits antioxidative and anti-inflammatory properties.
Epitalon is a synthetic tetrapeptide with anti-aging properties.1,2,3,4 Dietary administration of epitalon (0.00001% w w) reduces levels of lipid peroxidation products in aged D. melanogaster tissue homogenates.1 Epitalon (1 μg animal) delays age-related estrous shutdown and decreases the frequency of bone marrow cell chromosomal aberrations in female mice.2 It decreases spontaneous mammary gland and ovarian tumor development and metastasis in aged female mice.3 Epitalon also stimulates melatonin synthesis and normalizes the circadian rhythm of cortisol secretion in senescent female M. mulatta monkeys.4References1. Khavinson, V.K., and Myl'nikov, S.V. Effect of epithalone on the age-specific changes in the time course of lipid peroxidation in Drosophila melanogaster. Bull. Exp. Biol. Med. 130(11), 1116-1119 (2000).2. Anisimov, V.N., Khavinson, V.K., Popovich, I.G., et al. Effect of Epitalon on biomarkers of aging, life span and spontaneous tumor incidence in female Swiss-derived SHR mice. Biogerontology 4(4), 193-202 (2003).3. Kossoy, G., Anisimov, V.N., Ben-Hur, H., et al. Effect of the synthetic pineal peptide epitalon on spontaneous carcinogenesis in female C3H He mice. In Vivo 20(2), 253-257 (2006).4. Khavinson, V., Goncharova, N., and Lapin, B. Synthetic tetrapeptide epitalon restores disturbed neuroendocrine regulation in senescent monkeys. Neuro. Endocrinol. Lett. 22(4), 251-254 (2001). Epitalon is a synthetic tetrapeptide with anti-aging properties.1,2,3,4 Dietary administration of epitalon (0.00001% w w) reduces levels of lipid peroxidation products in aged D. melanogaster tissue homogenates.1 Epitalon (1 μg animal) delays age-related estrous shutdown and decreases the frequency of bone marrow cell chromosomal aberrations in female mice.2 It decreases spontaneous mammary gland and ovarian tumor development and metastasis in aged female mice.3 Epitalon also stimulates melatonin synthesis and normalizes the circadian rhythm of cortisol secretion in senescent female M. mulatta monkeys.4 References1. Khavinson, V.K., and Myl'nikov, S.V. Effect of epithalone on the age-specific changes in the time course of lipid peroxidation in Drosophila melanogaster. Bull. Exp. Biol. Med. 130(11), 1116-1119 (2000).2. Anisimov, V.N., Khavinson, V.K., Popovich, I.G., et al. Effect of Epitalon on biomarkers of aging, life span and spontaneous tumor incidence in female Swiss-derived SHR mice. Biogerontology 4(4), 193-202 (2003).3. Kossoy, G., Anisimov, V.N., Ben-Hur, H., et al. Effect of the synthetic pineal peptide epitalon on spontaneous carcinogenesis in female C3H He mice. In Vivo 20(2), 253-257 (2006).4. Khavinson, V., Goncharova, N., and Lapin, B. Synthetic tetrapeptide epitalon restores disturbed neuroendocrine regulation in senescent monkeys. Neuro. Endocrinol. Lett. 22(4), 251-254 (2001).
AMK is an active metabolite of the neurohormone melatonin .1,2,3,4It is formed from melatoninviathe metabolic intermediate AFMK that is then deformylated by catalase or formamidase.5,6AMK scavenges singlet oxygenin vitrowhen used at a concentration of 200 μM.1It inhibits the epinephrine- and arachidonic acid-induced production of prostaglandin E2and PGD2in ovine seminal vesicle microsomes in a concentration- and time-dependent manner, as well as LPS-induced increases in COX-2 levels in RAW 264.7 macrophages when used at a concentration of 500 μM.2,3AMK (20 mg kg) decreases MPTP-induced increases in lipid peroxidation in the cytosol and mitochondria from substantia nigra and striatum in a mouse model of MPTP-induced Parkinson’s disease.4 1.Schaefer, M., and Hardeland, R.The melatonin metabolite N1-acetyl-5-methoxykynuramine is a potent singlet oxygen scavengerJ. Pineal Res.46(1)49-52(2009) 2.Kelly, R.W., Amato, F., and Seamark, R.F.N-acetyl-5-methoxy kynurenamine, a brain metabolite of melatonin, is a potent inhibitor of prostaglandin biosynthesisBiochem. Biophys. Res. Commun.121(1)372-379(1984) 3.Mayo, J.C., Sainz, R.M., Tan, D.-X., et al.Anti-inflammatory actions of melatonin and its metabolites, N1-acetyl-N2-formyl-5-methoxykynuramine (AFMK) and N1-acetyl-5-methoxykynuramine (AMK), in macrophagesJ. Neuroimmunol.165(1-2)139-149(2005) 4.Tapias, V., Escames, G., López, L.C., et al.Melatonin and its brain metabolite N1-acetyl-5-methoxykynuramine prevent mitochondrial nitric oxide synthase induction in parkinsonian miceJ. Neurosci. Res.87(13)3002-3010(2009) 5.Tan, D.-X., Manchester, L.C., Reiter, R.J., et al.Melatonin directly scavenges hydrogen peroxide: A potentially new metabolic pathway of melatonin biotransformationFree Radic. Biol. Med.29(11)1177-1185(2000) 6.Hirata, F., Hayaishi, O., Tokuyama, T., et al.In vitro and in vivo formation of two new metabolites of melatoninJ. Biol. Chem.249(4)1311-1313(1974)