Phoenixin (PNX), a pleiotropic neuropeptide discovered in 2013, was initially introduced to the scientific community as a reproductive peptide (1). However, recent studies have revealed that PNX, by crossing the blood-brain barrier, exhibits protective effects in the cardiovascular system, nociception, inflammation, and oxidative stress, as well as physiological roles related to food intake, anxiety, and stress (2).  Phoenixin is an endogenous peptide expressed not only in the central nervous system, including the hypothalamus, pituitary gland, and spinal cord, but also in peripheral tissues such as the heart, kidneys, lungs, duodenum, jejunum, colon, pancreas, adipose tissue, and ovaries (2). Although not definitively proven, GPR173 is widely accepted as the most likely receptor for PNX (3). GPR173 is primarily expressed in the brain and ovaries. While PNX exists in various isoforms with amino acid lengths of 14, 17, 20, and 36, the bioactive forms are phoenixin-20 and phoenixin-14. PNX-20 expression is dominant in the hypothalamus, whereas PNX-14 is predominant in the heart and spinal cord (1, 4). Phoenixin has been demonstrated to possess analgesic properties when administered intrathecally (5). Additionally, when introduced intracerebroventricularly or infused into the hippocampus, it has been found to improve both memory formation and retention while also producing a dose-dependent anxiolytic effect (6). Furthermore, PNX is recognized for its involvement in gut-brain communication, similar to its function within the hypothalamic-pituitary-gonadal axis (7). Even though research on Phoenixin is still in the early stages, various in vivo and in vitro experimental studies have provided encouraging insights into its physiological functions. These findings could be beneficial for the pharmacological treatment of endocrine disorders, neurodegenerative diseases like Alzheimer’s and Parkinson’s, as well as a range of psychiatric and psychosomatic disorders such as anorexia nervosa and post-traumatic stress disorder, along with the increasing number of stress-related conditions like burnout syndrome and depression (3).

1.        Yosten G, Lyu R, Hsueh A, et al. A novel reproductive peptide, phoenixin. J Neuroendocr. 22013;25(2):206-215. doi:10.1111/j.1365-2826.2012.02381.x.A

2.        Liang H, Zhao Q, Lv S, Ji X. Regulation and physiological functions of phoenixin. Front Mol Biosci. 2022;9:956500. doi:10.3389/fmolb.2022.956500

3.        Friedrich T, Stengel A. Current state of phoenixin—the implications of the pleiotropic peptide in stress and its potential as a therapeutic target. Front Pharmacol. 2023;14(February):1-10. doi:10.3389/fphar.2023.1076800

4.        McIlwraith EK, Belsham DD. Phoenixin: Uncovering its receptor, signaling and functions. Acta Pharmacol Sin. 2018;39(5):774-778. doi:10.1038/aps.2018.13

5.        Lyu RM, Huang XF, Zhang Y, Dun SL, . Luo JJ, Chang JK DN. Phoenixin: a novel peptide in rodent sensory ganglia. Neuroscience. 2013;250:622-631. doi:10.1016/j.neuroscience.2013.07.057.Phoenixin

6.        Jiang JH, He Z, Peng YL, et al. Phoenixin-14 enhances memory and mitigates memory impairment induced by Aβ1-42 and scopolamine in mice. Brain Res. 2015;1629:298-308. doi:10.1016/j.brainres.2015.10.030

7.        Schalla MA, Stengel A. Phoenixin-A pleiotropic gut-brain peptide. Int J Mol Sci. 2018;19(6). doi:10.3390/ijms19061726