Effect of ellagic acid on BDNF/PI3K/AKT-mediated signaling pathways in mouse models of depression | ||
| Iranian Journal of Basic Medical Sciences | ||
| مقاله 11، دوره 28، شماره 4، تیر 2025، صفحه 493-497 اصل مقاله (194.83 K) | ||
| نوع مقاله: Original Article | ||
| شناسه دیجیتال (DOI): 10.22038/ijbms.2025.81230.17580 | ||
| نویسندگان | ||
| Aslı Hatice Bedel1، 2؛ Coskun Usta* 2 | ||
| 1Süleyman Demirel University Faculty of Pharmacy Department of Pharmacology, Türkiye | ||
| 2Akdeniz University Faculty of Medicine Department of Medicinal Pharmacology, Türkiye | ||
| چکیده | ||
| Objective(s): The aim of this study is to investigate the possible role of the hippocampal BDNF-PI3K-AKT signaling pathway in the antidepressant-like activity of ellagic acid (EA) in mice. Materials and Methods: Male BALB/C mice were divided into 5 groups; vehicle (0.1 ml/day), sertraline (5mg/kg), EA (1 mg/kg), EA+BKM120 (PI3K inhibitor), EA+MK2206 (AKT inhibitor). EA, sertraline and vehicle were injected intraperitoneally for 14 days. Locomotor activity was determined by open field test. The tail suspension test was used to detect the antidepressant-like effect. After behavioral tests, hippocampal tissue was obtained and Western blot analyzes were performed for BDNF and pAKT1. Results: Sertraline and EA provided a reduction in immobility time in the tail suspension test when compared with the control group. BKM120 and MK2206 administration reversed this effect of EA. No statistical difference was found between groups in terms of locomotor activity. EA treatment caused an increase in hippocampal BDNF and pAKT1 levels in mice. While inhibitory agent administrations did not affect the increase of BDNF induced by EA, MK2206 administration reversed the increase in pAKT1 observed with EA. Conclusion: It has shown that EA has an antidepressant-like effect in mice without changing locomotor activity, and this effect may be mediated by the BDNF-PI3K-AKT signaling pathway. | ||
| کلیدواژهها | ||
| AKT؛ BDNF؛ Depression؛ Ellagic acid؛ PI3K | ||
| مراجع | ||
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1. Rush AJ. Unipolar major depression in adults: Choosing initial treatment. Retrieved from 2022; https://www.uptodate.com/contents/unipolar-major-depression- in-adults-choosing-initial-treatment. 2. Goethe JW, Woolley SB, Cardoni AA, Woznicki BA, Pie DA. Selective serotonin reuptake inhibitor discontinuation: Side effects and other factors that influence medication adherence. J Clin Psychopharmacol 2007; 27: 451-458. 3. Marasine NR, Sankhi S. Factors associated with antidepressant medication non- adherence. Turk J Pharm Sci 2021; 18: 242-249. 4. Nasrolahi A, Javaherforooshzadeh F, Jafarzadeh-Gharehziaaddin, Mahmoudi J, Asl KD, Shabani Z. Therapeutic potential of neurotrophic factors in Alzheimer’s disease. Mol Biol Rep 2022; 49: 2345-2357. 5. Sathyanesan M, Newton SS. Antidepressant-like effects of trophic factor receptor signaling. Front Mol Neurosci 2022; 15: 958797-958811. 6. Gupta VK, You Y, Gupta VB, Klistorner A, Graham SL. Trkb receptor signalling: Implications in neurodegenerative, psychiatric and proliferative disorders. Int J Mol Sci 2013; 14: 10122-10142. 7. Ghigo A, Morello F, Perino A, Hirsch E. Phosphoinositide 3-kinases in health and disease. Subcell Biochem 2012; 58: 183-213. 8. Zhou C, Zhong J, Zou B, Fang L, Chen J, Deng X, et al. Meta-analyses of comparative efficacy of antidepressant medications on peripheral bdnf concentration in patients with depression. PLoS One 2017; 12: e0172270-172287. 9. Pelosof R, Santos LAD, Farhat LC, Gattaz WF, Talib L, Brunoni AR. BDNF blood levels after electroconvulsive therapy in patients with mood disorders: An updated systematic review and meta-analysis. World J Biol Psychiatry 2022: 24: 24-33. 10. Do Carmo Barbosa Mendes De Vasconcelos M, Bennett RN, Rosa EA, Ferreira Cardoso JV. Primary and secondary metabolite composition of kernels from three cultivars of Portuguese chestnut (Castanea sativa mill.) at different stages of industrial transformation. J Agric Food Chem 2007; 55: 3508-3516. 11. Ribeiro B, Valentão P, Baptista P, Seabra RM, Andrade PB. Phenolic compounds, organic acids profiles and antioxidative properties of beefsteak fungus (Fistulina hepatica). Food Chem Toxicol 2007; 45: 1805-1813. 12. Truzzi F, Tibaldi C, Zhang Y, Dinelli G, Eros DA. An overview on dietary polyphenols and their biopharmaceutical classification system (BCS). Int J Mol Sci 2021; 22: 5514-5537. 13. Huang X, Li W, You B, Tang W, Gan T, Feng C, et al. Serum metabonomic study on the antidepressant-like effects of ellagic acid in a chronic unpredictable mild stress-induced mouse model. J Agric Food Chem 2020; 68: 9546-9556. 14. Bedel HA, Kencebay Manas C, Özbey G, Usta C. The antidepressant-like activity of ellagic acid and its effect on hippocampal brain-derived neurotrophic factor levels in mouse depression models. Nat Prod Res 2018; 32: 2932-2935. 15. Yusha’u Y, Muhammad UA, Nze M, Egwuma JM, Igomu OJ, Abdulkadir M. Modulatory role of rutin supplement on open space forced swim test murine model of depression. Niger J Physiol Sci 2017; 32: 201-205. 16. Steru L, Chermat R, Thierry B, Simon P. The tail suspension test: A new method for screening antidepressants in mice. Psychopharmacology (Berl) 1985; 85: 367-370. 17. Zhao XP, Li H, Dai RP. Neuroimmune crosstalk through brain-derived neurotrophic factor and its precursor pro-BDNF: New insights into mood disorders. World J Psychiatry 2022; 12: 379-392. 18. Can ÖD, Turan N, Demir Özkay Ü, Öztürk Y. Antidepressant-like effect of gallic acid in mice: Dual involvement of serotonergic and catecholaminergic systems. Life Sci 2017; 190: 110-117. 19. Diniz LRL, Souza MTS, Barboza JN, Almeida RN, Sousa DP. Antidepressant potential of cinnamic acids: Mechanisms of action and perspectives in drug development. Molecules 2019; 24: 4469-4481. 20. Zuccari G, Baldassari S, Ailuno G, Turrini F, Alfei S, Caviglioli G. Formulation strategies to improve oral bioavailability of ellagic acid. Appl Sci 2020; 10: 3353-3380. 21. Kilic I, Yeşiloğlu Y, Bayrak Y. Spectroscopic studies on the antioxidant activity of ellagic acid. Spectrochim Acta A Mol Biomol Spectrosc 2014; 130: 447-452. 22. Bhattacharjee A, Kulkarni VH, Chakraborty M, Habbu PV, Ray A. Ellagic acid restored lead-induced nephrotoxicity by anti-inflammatory, anti-apoptotic and free radical scavenging activities. Heliyon 2021; 7: e05921-5928. 23. Mohammadinejad A, Mohajeri T, Aleyaghoob G, Heidarian F, Kazemi Oskuee R. Ellagic acid as a potent anticancer drug: A comprehensive review on in vitro, in vivo, in silico, and drug delivery studies. Biotechnol Appl Biochem 2022; 69: 2323-2356. 24. Tao W, Dong Y, Su Q, Wang H, Chen Y, Xue W, et al. Liquiritigenin reverses depression-like behavior in unpredictable chronic mild stress-induced mice by regulating Pİ3K/AKT/mTOR mediated BDNF/TrKB pathway. Behav Brain Res 2016; 308: 177-186. 25. Park SJ, Jaiswal V, Lee HJ. Dietary intake of flavonoids and carotenoids is associated with antidepressive symptoms: Epidemiological study and in silico-mechanism analysis. Antioxidants (Basel) 2021; 11: 53-73. 26. Amidfar M, Réus GZ, Quevedo J, Kim YK, Arbabi M. Effect of co-administration of memantine and sertraline on the antidepressant-like activity and brain-derived neurotrophic factor (bdnf) levels in the rat brain. Brain Res Bull 2017; 128: 29-33. 27. Mu RH, Fang XY, Wang SS, Li CF, Chen SM, Chen XM, et al. Antidepressant-like effects of standardized gypenosides: Involvement of brain- derived neurotrophic factor signaling in hippocampus. Psychopharmacology (Berl) 2016; 233: 3211-3221. 28. Zhou Z, Chen H, Tang X, He B, Gu L, Feng H. Total saikosaponins attenuates depression-like behaviors induced by chronic unpredictable mild stress in rats by regulating the Pİ3K/AKT/NF-ΚB signaling axis. Evid Based Complement Alternat Med 2022; 2022: 4950414. 29. Pochwat B, Szewczyk B, Kotarska K, Rafało-Ulińska A, Siwiec M, Sowa JE, et al. Hyperforin potentiates antidepressant-like activity of lanicemine in mice. Front Mol Neurosci 2018; 11: 456-472. 30. Chuang HW, Wei IH, Lin FY, Li CT, Chen KT, Tsai MH, et al. Roles of akt and erk in mtor-dependent antidepressant effects of vanillic acid. ACS Omega 2020; 5: 3709-3716. 31. Roy A, Skibo J, Kalume F, Ni J, Rankin S, Lu Y, et al. Mouse models of human PİK3CA-related brain overgrowth have acutely treatable epilepsy. ELife 2015; 4: e12703-12725. 32. Mao XY, Zhou HH, Li X, Liu ZQ. Huperzine a alleviates oxidative glutamate toxicity in hippocampal ht22 cells via activating BDNF/TRKB-dependent Pİ3K/AKT/MTOR signaling pathway. Cell Mol Neurobiol 2016; 36: 915-925. 33. Alfaris NA, Alshammari GM, Altamimi JZ, Aljabryn DH, Alagal RI, Aldera H, et al. Ellagic acid prevents streptozotocin-induced hippocampal damage and memory loss in rats by stimulating NRF2 and nuclear factor-κb, and activating insulin receptor substrate/Pİ3K/AKT axis. J Physiol Pharmacol 2021; 72: 503-515. 34. Hajiluian G, Karegar SJ, Shidfar F, Aryaeian N, Salehi M, Lotfi T, et al. The effects of ellagic acid supplementation on neurotrophic, inflammation, and oxidative stress factors, and indoleamine 2, 3-dioxygenase gene expression in multiple sclerosis patients with mild to moderate depressive symptoms: A randomized, triple-blind, placebo-controlled trial. Phytomedicine 2023; 121: 155094. 35. Hosseini SH, Zarghami M, Haghighian HK, Roochi AB, Abediankenari S, Kargar-Soleimanabad S, et al. Effects of ellagic acid supplementation on antioxidant status and symptom ımprovement in patients with major depressive disorder: A double-blind randomized clinical trial. Iran J Psychiatry Behav Sci 2024; 18:e144775. | ||
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