Effect of Hesperidin on Memory Impairments Induced by Valproic acid in Rats
Keywords:
Hesperidin; Valproic acid; Memory impairmentAbstract
Background and objective: Decreasing of neurogenesis in the subgranular zone (SGZ) of the dentate gyrus (DG) in the hippocampus is linked to memory deficits. In animal studies, treatment with valproic acid (VPA) impairs neurogenesis in the SGZ resulting in memory impairment. Hesperidin (Hsd), a plant flavanone, is a natural extract, which enhances learning and memory. Therefore, the aim of this study was to investigate the effect of Hsd on memory impairment in rats induced by VPA.
Methods: Male Sprague Dawley rats were divided into 4 groups (6 animals/group) including vehicle, VPA, Hsd and VPA+Hsd groups. VPA (300 mg/kg) was administrated by intraperitoneal (i.p.) injection twice daily for 14 days. Hsd (100 mg/kg/day) was administrated by oral gavage once a day for 21 days. Body weight was weighed and recorded every day. Three days after the treatment, rats were tested for memory using the novel object location (NOL) and novel object recognition (NOR) tests.
Results: The results showed that the body weight and total exploration time were not significantly different among groups in both NOL and NOR tests (p>0.05). In the NOL test, rats in the vehicle, Hsd and VPA+Hsd groups could significantly discriminate between the novel and familiar locations (p<0.05). In the NOR test, similarly, rats in the vehicle, Hsd and VPA+Hsd groups could significantly discriminate between the novel and familiar objects (p<0.05). In contrast, rats in the VPA group could not significantly performed in both tests.
Conclusion: This study demonstrates that hesperidin could improve the memory impairments induced by valproic acid.
References
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2. ELBeltagy M, Mustafa S, Umka J, Lyons L, Salman A, Gloria Tu C-Y, et al. Fluoxetine improves the memory deficits caused by the chemotherapy agent 5-fluorouracil. Behav Brain Res 2010; 208: 112–117.
3. ELBeltagy M, Mustafa S, Umka J, Lyons L, Salman A, Dormon K, et al. The effect of 5-fluorouracil on the long term survival and proliferation of cells in the rat hippocampus. Brain Res Bull 2012; 88: 514–518.
4. Umka J, Mustafa S, ElBeltagy M, Thorpe A, Latif L, Bennett G, et al. Valproic acid reduces spatial working memory and cell proliferation in the hippocampus. Neuroscience 2010; 166: 15–22.
5. Lyons L, ELBeltagy M, Bennett G, Wigmore P. The effects of cyclophosphamide on hippocampal cell proliferation and spatial working memory in rat. Homayouni R, editor. PLoS ONE 2011; 6: e21445.
6. Umka Welbat J, Sirichoat A, Chaijaroonkhanarak W, Prachaney P, Pannangrong W, Pakdeechote P, et al. Asiatic acid prevents the deleterious effects of valproic acid on cognition and hippocampal cell proliferation and survival. Nutrients 2016; 8: 303.
7. Welbat JU, Chaisawang P, Chaijaroonkhanarak W, Prachaney P, Pannangrong W, Sripanidkulchai B, et al. Kaempferia parviflora extract ameliorates the cognitive impairments and the reduction in cell proliferation induced by valproic acid treatment in rats. Ann Anat - Anat Anz 2016; 206: 7–13.
8. Aranarochana A, Chaisawang P, Sirichoat A, Pannangrong W, Wigmore P, Welbat JU. Protective effects of melatonin against valproic acid-induced memory impairments and reductions in adult rat hippocampal neurogenesis. Neuroscience 2019; 406: 580–593.
9. Lledo P-M, Alonso M, Grubb MS. Adult neurogenesis and functional plasticity in neuronal circuits. Nat Rev Neurosci 2006; 7: 179–193.
10. Ming G, Song H. Adult neurogenesis in the mammalian brain: significant answers and significant questions. Neuron 2011; 70: 687–702.
11. Garg A, Garg S, Zaneveld LJD, Singla AK. Chemistry and pharmacology of the citrus bioflavonoid hesperidin. Phytother Res 2001; 15: 655–669.
12. Crozier A, Jaganath IB, Clifford MN. Dietary phenolics: chemistry, bioavailability and effects on health. Nat Prod Rep 2009; 26: 1001.
13. Cho J. Antioxidant and neuroprotective effects of hesperidin and its aglycone hesperetin. Arch Pharm Res 2006; 29: 699–706.
14. Thenmozhi AJ, Raja TRW, Janakiraman U, Manivasagam T. Neuroprotective Effect of hesperidin on aluminum chloride induced Alzheimer’s disease in Wistar rats. Neurochem Res 2015; 40: 767–776.
15. Hajialyani M, Hosein Farzaei M, Echeverría J, Nabavi S, Uriarte E, Sobarzo-Sánchez E. Hesperidin as a neuroprotective agent: A review of animal and clinical evidence. Molecules 2019; 24: 648.
16. Naewla S, Sirichoat A, Pannangrong W, Chaisawang P, Wigmore P, Welbat JU. Hesperidin alleviates methotrexate-induced memory deficits via hippocampal neurogenesis in adult rats. Nutrients 2019; 11: 936.
17. Nissinen J, Pitkänen A. Effect of antiepileptic drugs on spontaneous seizures in epileptic rats. Epilepsy Res 2007; 73: 181–191.
18. Dix SL, Aggleton JP. Extending the spontaneous preference test of recognition: evidence of object-location and object-context recognition. Behav Brain Res 1999; 99: 191–200.
19. de Oliveira D, Dourado GKZS, Cesar T. Hesperidin associated with continuous and interval swimming improved biochemical and oxidative biomarkers in rats. J Int Soc Sports Nutr 2013; 10: 27.
20. Tomazini Gonçalves T, Lazaro C, De Mateo F, Campos M, Mezencio J, Claudino M, et al. Effects of glucosyl-hesperidin and physical training on body weight, plasma lipids, oxidative status and vascular reactivity of rats fed with high-fat diet. Diabetes Metab Syndr Obes Targets Ther 2018; 11: 321–332.
21. Kotajima-Murakami H, Kobayashi T, Kashii H, Sato A, Hagino Y, Tanaka M, et al. Effects of rapamycin on social interaction deficits and gene expression in mice exposed to valproic acid in utero. Mol Brain 2019;12: 3.
22. Kessels RPC, de Haan EHF, Kappelle LJ, Postma A. Varieties of human spatial memory: a meta-analysis on the effects of hippocampal lesions. Brain Res Rev 2001; 35: 295–303.
23. Pourmemar E, Majdi A, Haramshahi M, Talebi M, Karimi P, Sadigh-Eteghad S. Intranasal Cerebrolysin attenuates learning and memory impairments in D-galactose-induced senescence in mice. Exp Gerontol 2017; 87: 16–22.
24. Welbat JU, Naewla S, Pannangrong W, Sirichoat A, Aranarochana A, Wigmore P. Neuroprotective effects of hesperidin against methotrexate-induced changes in neurogenesis and oxidative stress in the adult rat. Biochem Pharmacol 2020; 178: 114083.
25. Prajit R, Sritawan N, Suwannakot K, Naewla S, Aranarochana A, Sirichoat A, et al. Chrysin protects against memory and hippocampal neurogenesis depletion in D-galactose-induced aging in rats. Nutrients 2020; 12: 1100.
26. Sritawan N, Prajit R, Chaisawang P, Sirichoat A, Pannangrong W, Wigmore P, et al. Metformin alleviates memory and hippocampal neurogenesis decline induced by methotrexate chemotherapy in a rat model. Biomed Pharmacother 2020; 131: 110651.
27. Patestas MA, Gartner LP. A textbook of neuroanatomy. Malden, MA: Blackwell Pub; 2006: 454.
28. Takuma K, Hara Y, Kataoka S, Kawanai T, Maeda Y, Watanabe R, et al. Chronic treatment with valproic acid or sodium butyrate attenuates novel object recognition deficits and hippocampal dendritic spine loss in a mouse model of autism. Pharmacol Biochem Behav 2014; 126: 43–49.
29. Welbat JU, Sangrich P, Sirichoat A, Chaisawang P, Chaijaroonkhanarak W, Prachaney P, et al. Fluoxetine prevents the memory deficits and reduction in hippocampal cell proliferation caused by valproic acid. J Chem Neuroanat 2016; 78: 112–118.
30. Wang D, Liu L, Zhu X, Wu W, Wang Y. Hesperidin alleviates cognitive impairment, mitochondrial dysfunction and oxidative stress in a mouse model of Alzheimer’s disease. Cell Mol Neurobiol 2014; 34: 1209–1221.
31. Kitabatake Y, Sailor KA, Ming G, Song H. Adult neurogenesis and hippocampal memory function: new cells, more plasticity, new memories? Neurosurg Clin N Am 2007; 18: 105–113.
32. Tamilselvam K, Braidy N, Manivasagam T, Essa MM, Prasad NR, Karthikeyan S, et al. Neuroprotective effects of hesperidin, a plant flavanone, on rotenone-induced oxidative stress and apoptosis in a cellular model for Parkinson’s disease. Oxid Med Cell Longev 2013; 2013: 1–11.
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Published
2021-04-07
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Kaewngam S, Anosri T, Prajit R, Suwannakot K, Sritawan N, Aranarochana A, Sirichoat1 A, Pannangrong W, Umka Welbat J. Effect of Hesperidin on Memory Impairments Induced by Valproic acid in Rats. SRIMEDJ [Internet]. 2021 Apr. 7 [cited 2024 Nov. 22];36(2):142-8. Available from: https://li01.tci-thaijo.org/index.php/SRIMEDJ/article/view/249574
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