The Mechanism of Chrysoeriol in Improving Depression-like Behavior in Mice by Inhibiting Neuroinflammation: A Network Pharmacology Study
Abstract
This study aimed to investigate the effects and mechanisms of Chrysoeriol (CHR) in improving depression-like behavior in mice.
Network pharmacology analysis was conducted to identify CHR-related targets and signaling pathways associated with depression and neuroinflammation. The chronic unpredictable mild stress (CUMS) method was used to construct a depression mouse model. After CHR intervention, behavioral changes were assessed using the elevated plus maze and open field tests. Cortical proinflammatory cytokine levels were measured using enzyme-linked immunosorbent assay (ELISA) kits, and pathological changes were examined by hematoxylin and eosin (H&E) and Nissl staining.
Network pharmacology identified AKT1 among the core predicted targets of CHR. Elevated plus maze and open field test results indicated that CHR improved depression-like behavior in mice. CHR reduced neuroinflammatory cytokine levels and attenuated tissue and neuronal damage.
CHR alleviated CUMS-induced depression-like behaviors and reduced neuroinflammation and neuronal damage. Network pharmacology identified predicted core targets, including AKT1. Further molecular verification and safety evaluation are required to validate its antidepressant potential.
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25. Zoubovsky SP, Hoseus S, Tumukuntala S, Rupprecht R, Wotjak CT, Murgatroyd C. Chronic psychosocial stress during pregnancy affects maternal behavior and neuroendocrine function and modulates hypothalamic CRH and nuclear steroid receptor expression. Transl Psychiatry. 2020;10:6.
2. Liu Q, He H, Yang J, Feng X, Zhao F, Lyu J, et al. Changes in the global burden of depression from 1990 to 2017: findings from the Global Burden of Disease study. J Psychiatr Res. 2020;126:134–40.
3. Kalin NH. New insights into major depression and the treatment of bipolar depression. Am J Psychiatry. 2021;178(12):1071–4.
4. Pandey GN, Rizavi HS, Zhang H, Ren X, Bhaumik R, Dwivedi Y. Abnormal protein and mRNA expression of inflammatory cytokines in the prefrontal cortex of depressed individuals who died by suicide. J Psychiatry Neurosci. 2018;43(6):376–85.
5. Bouças AP, Rheinheimer J, Lagopoulos J. Why severe COVID-19 patients are at greater risk of developing depression: a molecular perspective. Neuroscientist. 2022;28(1):11–9.
6. Jabbi M, Arasappan D, Eickhoff SB, Cattaneo A, Höfle M, Daskalakis ZJ, et al. Neuro-transcriptomic signatures for mood disorder morbidity and suicide mortality. J Psychiatr Res. 2020;127:62–74.
7. Barnes J, Mondelli V, Pariante CM. Genetic contributions of inflammation to depression. Neuropsychopharmacology. 2017;42(1):81–98.
8. Köhler CA, Freitas TH, Maes M, de Andrade NQ, Liu CS, Fernandes BS, et al. Peripheral cytokine and chemokine alterations in depression: a meta-analysis of 82 studies. Acta Psychiatr Scand. 2017;135(5):373–87.
9. Syed SA, Beurel E, Loewenstein DA, Lowell JA, Craighead WE, Dunlop BW, et al. Defective inflammatory pathways in never-treated depressed patients are associated with poor treatment response. Neuron. 2018;99(5):914–24.
10. Lamers F, Milaneschi Y, de Jonge P, Giltay EJ, Penninx BWJH. Metabolic and inflammatory markers: associations with individual depressive symptoms. Psychol Med. 2018;48(7):1102–10.
11. Lushchak VI, Duszenko M, Gospodaryov DV, Garaschuk O. Oxidative stress and energy metabolism in the brain: midlife as a turning point. Antioxidants (Basel). 2021;10(11):1715.
12. Kowalczyk P, Sulejczak D, Kleczkowska P, Bukowska-Ośko I, Kucia M, Popiel M, et al. Mitochondrial oxidative stress—a causative factor and therapeutic target in many diseases. Int J Mol Sci. 2021;22(24):13384.
13. Szebeni A, Szebeni K, DiPeri TP, Johnson LA, Stockmeier CA, Crawford JD, et al. Elevated DNA oxidation and DNA repair enzyme expression in brain white matter in major depressive disorder. Int J Neuropsychopharmacol. 2017;20(5):363–73.
14. Jiménez-Fernández S, Gurpegui M, Garrote-Rojas D, Gutiérrez-Rojas L, Carretero MD, Correll CU, et al. Oxidative stress parameters and antioxidants in adults with unipolar or bipolar depression versus healthy controls: systematic review and meta-analysis. J Affect Disord. 2022;314:211–21.
15. Kong Y, Liu C, Zhang C, Wang Y, Li X, Yang X. Association between serum uric acid levels and suicide attempts in adolescents and young adults with major depressive disorder: a retrospective study. Neuropsychiatr Dis Treat. 2022;18:1469–77.
16. Zhang K, Bai Y, Song T, Liu H, Li Y, Chen Y. In vivo and in vitro evidence of protective effects of a natural flavone on rat myocardial ischemia-reperfusion and hypoxia-reoxygenation injuries. J Cardiovasc Pharmacol Ther. 2013;18(1):31–6.
17. Wu JY, Chen YJ, Bai L, Liu Y, Fu X, Zhu PL, et al. Chrysoeriol ameliorates TPA-induced acute skin inflammation in mice and inhibits NF-κB and STAT3 pathways. Phytomedicine. 2020;68(12):153173.
18. Choi DY, Lee JY, Kim MR, Woo ER, Kim YG, Kang KW, et al. Chrysoeriol potently inhibits the induction of nitric oxide synthase by blocking AP-1 activation. J Biomed Sci. 2005;12(6):949–59.
19. Limboonreung T, Tuchinda P, Chongthammakun S. Chrysoeriol mediates mitochondrial protection via PI3K/Akt pathway in MPP+-treated SH-SY5Y cells. Neurosci Lett. 2020;714(14):134545.
20. Wigner P, Synowiec E, Czarny P, Bijak M, Talarowska M, Galecki P, et al. Effects of venlafaxine on the expression level and methylation status of genes involved in oxidative stress in rats exposed to a chronic mild stress. J Cell Mol Med. 2020;24(10):5675–94.
21. Celikbilek A, Gocmen AY, Tanik N, Borekci E, Zararsiz G, Benli S. Serum lipid peroxidation markers are correlated with those in brain samples in different stress models. Acta Neuropsychiatr. 2014;26(1):51–7.
22. Belvederi Murri M, Pariante C, Mondelli V, Masotti M, Atti AR, Mellacqua Z, et al. HPA axis and aging in depression: systematic review and meta-analysis. Psychoneuroendocrinology. 2014;41(5):46–62.
23. Du X, Pang TY. Is dysregulation of the HPA-axis a core pathophysiology mediating co-morbid depression in neurodegenerative diseases? Front Psychiatry. 2015;6:32.
24. Alcocer-Gómez E, de Miguel M, Casas-Barquero N, Núñez-Vasco J, Sánchez-Alcázar JA, Fernández-Rodríguez A, et al. NLRP3 inflammasome is activated in mononuclear blood cells from patients with major depressive disorder. Brain Behav Immun. 2014;36:111–7.
25. Zoubovsky SP, Hoseus S, Tumukuntala S, Rupprecht R, Wotjak CT, Murgatroyd C. Chronic psychosocial stress during pregnancy affects maternal behavior and neuroendocrine function and modulates hypothalamic CRH and nuclear steroid receptor expression. Transl Psychiatry. 2020;10:6.
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| Issue | Articles in Press | |
| Section | Original Article(s) | |
| Keywords | ||
| Chrysoeriol Depression Network pharmacology Neuroinflammation | ||
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How to Cite
1.
Kang Z, Zhang L, Lian C. The Mechanism of Chrysoeriol in Improving Depression-like Behavior in Mice by Inhibiting Neuroinflammation: A Network Pharmacology Study. Iran J Allergy Asthma Immunol. 2026;:1-13.
