(Gly14)-Humanin (human) is a potent analogue of Humanin, with highly neuroprotective activity[1]. (Gly14)-Humanin activates the Nrf2/GPX4 pathway, which reduces cellular oxidative stress and inhibits ferroptosis, thereby alleviating oligoasthenozoospermia in mice[2]. (Gly14)-Humanin has been widely used in vascular endothelial research to prevent lipid aggregation and cell death[3].
In vitro, (Gly14)-Humanin (0.1µM) was pre-treated for 6 hours, which protected PC12 cells from cell death induced by Aβ25-35, restored mitochondrial membrane potential and blocked the release of cytochrome c[4]. 1µM of (Gly14)-Humanin pretreatment for 3 hours inhibited apoptosis in human umbilical vein endothelial cells (HUVECs) triggered by high glucose (50mM) and reduced ROS production and PARP expression[5].
In vivo, (Gly14)-Humanin treatment via a single injection (i.c.v.) at a dose of 1000pmol (5µl) within 30 minutes improved scopolamine-caused learning and memory deficits in mice[6]. Continuous intraperitoneal injection of (Gly14)-Humanin (10mg/kg/day) for 6 consecutive weeks improved ovarian function and body weight in a mouse model of primary ovarian insufficiency and alleviated ovarian oxidative stress[7]. (Gly14)-Humanin (0.1µg) was administered (i.p.) every other day for 3 months, which improved the cognitive deficits in the middle-aged APPswe/PS1dE9 mice and reduced Aβ plaque deposition and alleviated neuroinflammation[8].
References:
[1] Wang T, Zhang L, Zhang M, et al. [Gly14]-Humanin reduces histopathology and improves functional outcome after traumatic brain injury in mice[J]. Neuroscience, 2013, 231: 70-81.
[2] Liu Y, Feng Q, Zou L, et al. Oligoasthenozoospermia is alleviated in a mouse model by [Gly14]‐humanin‐mediated attenuation of oxidative stress and ferroptosis[J]. Andrology, 2025, 13(6): 1541-1555.
[3] Ding Y, Feng Y, Zhu W, et al. [Gly14]‐Humanin Prevents Lipid Deposition and Endothelial Cell Apoptosis in a Lectin‐like Oxidized Low‐density Lipoprotein Receptor‐1‐Dependent Manner[J]. Lipids, 2019, 54(11-12): 697-705.
[4] Jin H, Liu T, Wang W X, et al. Protective effects of [Gly14]-Humanin on β-amyloid-induced PC12 cell death by preventing mitochondrial dysfunction[J]. Neurochemistry international, 2010, 56(3): 417-423.
[5] Xie Y, Liu Z, Li X, et al. Protection effect of [Gly14]-Humanin from apoptosis induced by high glucose in human umbilical vein endothelial cells[J]. Diabetes research and clinical practice, 2014, 106(3): 560-566.
[6] Mamiya T, Ukai M. [Gly14]‐Humanin improved the learning and memory impairment induced by scopolamine in vivo[J]. British journal of pharmacology, 2001, 134(8): 1597-1599.
[7] Huang J, Feng Q, Zou L, et al. [Gly14]-humanin exerts a protective effect against D-galactose-induced primary ovarian insufficiency in mice[J]. Reproductive BioMedicine Online, 2024, 48(2): 103330.
[8] Zhang W, Zhang W, Li Z, et al. S14G-humanin improves cognitive deficits and reduces amyloid pathology in the middle-aged APPswe/PS1dE9 mice[J]. Pharmacology Biochemistry and Behavior, 2012, 100(3): 361-369.