Epithalon is a tetrapeptide that induces telomerase activity and telomere elongation [1]. Epithalon can penetrate through the cell membrane and enter the nucleus, where Epithalon increases the transcriptional levels of Nestin and GAP43[2]. Epithalon has been widely used to stimulate evening melatonin production and normalize circadian rhythms of cortisol production in old monkeys[3].
In vitro, Epithalon treatment at 0.01μg/ml for 7 days significantly upregulated the expression of neurogenesis-related genes and the synthesis of β-tubulin III and Doublecortin in human gingival mesenchymal stem cells (hGMSCs)[4]. Treatment with 50nM Epithalon for 24h significantly prevented the decrease in neprilysin and insulin-degrading enzyme expression induced by hypoxia in NB7 neuroblastoma cells[5]. Treatment with 400ng/ml Epithalon for 24h significantly alleviated UV-induced oxidative stress and increased the expression of SOD-1, NQO1, and CATALASE genes in dermal fibroblasts[6].
In vivo, Epithalon treatment via oral administration at a dose of 100µg/day for one month significantly improved the transport properties of the small intestine in aged rats and promoted active glucose accumulation in the proximal and distal segments of the small intestine[7]. Epithalon (1µg) administered subcutaneously five times a week for six months significantly suppressed tumor growth in female transgenic FVB/N mice carrying the breast cancer gene HER-2/neu[8].
References:
[1] Khavinson V K, Bondarev I E, Butyugov A A. Epithalon peptide induces telomerase activity and telomere elongation in human somatic cells[J]. Bulletin of Experimental Biology and Medicine, 2003, 135(6): 590-592.
[2] Araj S K, Brzezik J, Mądra-Gackowska K, et al. Overview of Epitalon—Highly Bioactive Pineal Tetrapeptide with Promising Properties[J]. International Journal of Molecular Sciences, 2025, 26(6): 2691.
[3] Khavinson V K, Konovalov S S, Yuzhakov V V, et al. Modulating effects of epithalamin and epithalon on the functional morphology of the spleen in old pinealectomized rats[J]. Bulletin of Experimental Biology and Medicine, 2001, 132(5): 1116-1120.
[4] Khavinson V, Diomede F, Mironova E, et al. AEDG peptide (Epitalon) stimulates gene expression and protein synthesis during neurogenesis: possible epigenetic mechanism[J]. Molecules, 2020, 25(3): 609.
[5] Kozina L S, Kochkina E G, Nalivaeva N N, et al. The effects of vilon and epithalon peptides on the expression of neprilysin and insulin-degrading enzyme in human neuroblastoma NB7 cells under normal and hypoxic conditions[J]. Neurochemical Journal, 2008, 2(1): 69-71.
[6] Gutop E O, Linkova N S, Kozhevnikova E O, et al. AEDG Peptide Prevents Oxidative Stress in the Model of Induced Aging of Skin Fibroblasts[J]. Advances in Gerontology, 2022, 12(2): 143-148.
[7] Khavinson V K, Egorova V V, Timofeeva N M, et al. Effect of Vilon and Epithalon on glucose and glycine absorption in various regions of small intestine in aged rats[J]. Bulletin of Experimental Biology and Medicine, 2002, 133(5): 494-496.
[8] Anisimov V N, Khavinson V K, Alimova I N, et al. Epithalon decelerates aging and suppresses development of breast adenocarcinomas in transgenic her-2/neu mice[J]. Bulletin of Experimental Biology and Medicine, 2002, 134(2): 187-190.
Epithalon是一种四肽，能够诱导端粒酶活性和端粒延长[1]。Epithalon可穿透细胞膜进入细胞核，并在其中提高巢蛋白（Nestin）和生长相关蛋白43（GAP43）的转录水平[2]。Epithalon已被广泛用于刺激老年猴的夜间褪黑素生成，并使皮质醇分泌的昼夜节律恢复正常[3]。
在体外，使用0.01µg/ml的Epithalon处理人牙龈间充质干细胞（hGMSCs）7天，显著上调了神经发生相关基因的表达以及β-tubulin III和Doublecortin的合成[4]。使用50nM的Epithalon处理NB7神经母细胞瘤细胞24小时，显著预防了缺氧诱导的脑啡肽酶和胰岛素降解酶表达下降[5]。使用400ng/ml的Epithalon处理真皮成纤维细胞24小时，显著减轻了紫外线诱导的氧化应激，并增加了SOD-1、NQO1和CATALASE基因的表达[6]。
在体内，每日口服给予100µg的Epithalon，持续一个月，显著改善了老年大鼠小肠的转运特性，并促进了葡萄糖在近端和远端小肠段的主动积累[7]。每周五次皮下注射1µg的Epithalon，持续六个月，显著抑制了携带乳腺癌基因HER-2/neu的雌性转基因FVB/N小鼠的肿瘤生长[8]。