Beneficial Effect of Rosmarinic Acid on Neurobehavioral Deficits Induced by L-methionine in Adult Rats

Authors

  • Jirawadee Chaithum Department of Anatomy, Faculty of Medicine, and Neurogenesis Research Group, Khon Kaen University, Khon Kaen 40002, Thailand
  • Oabnithi Dornlakorn Department of Anatomy, Faculty of Medicine, and Neurogenesis Research Group, Khon Kaen University, Khon Kaen 40002, Thailand
  • Nataya Sritawan Department of Anatomy, Faculty of Medicine, and Neurogenesis Research Group, Khon Kaen University, Khon Kaen 40002, Thailand
  • Anusara Aranarochana Department of Anatomy, Faculty of Medicine, and Neurogenesis Research Group, Khon Kaen University, Khon Kaen 40002, Thailand
  • Jariya Umka Welbat Department of Anatomy, Faculty of Medicine, and Neurogenesis Research Group, Khon Kaen University, Khon Kaen 40002, Thailand
  • Apiwat Sirichoat Department of Anatomy, Faculty of Medicine, and Neurogenesis Research Group, Khon Kaen University, Khon Kaen 40002, Thailand

Keywords:

Rosmarinic acid, L-methionine, spatial memory, recognition memory

Abstract

Background and Objective: Food consumption that contains large quantities of L-methionine (L-met), an essential amino acid can cause oxidative stress by increasing levels of homocysteine. High levels of homocysteine contribute to neuronal cell damage, which can lead to memory impairment. Rosmarinic acid (RA) is a phenolic compound widely distributed in rosemary, thyme and basil. Several studies revealed that rosmarinic acid has the ability to enhance learning and memory function. Therefore, this study was designed to determine the neuroprotective effect of rosmarinic acid against L-methionine-induced memory impairments.

Methods: Male Sprague Dawley rats were divided into 6 groups: control, L-met (1.7 g/kg), RA (10 and 30 mg/kg) and L-met + RA (10 and 30 mg/kg) groups. Subjects were treated once a time per day for 28 days. Body weight was recorded every day. Before and after drug administration, spatial and recognition memory were investigated using the novel object location (NOL) and the novel object recognition (NOR) tests, respectively.

Results: The results revealed that rosmarinic acid and L-met did not have a negative effect on the body weight and locomotor activity. Whereas NOL and NOR tests revealed that control, RA (10 and 30 mg/kg), L-met + RA (10 and 30 mg/kg) groups were significantly different in the time spent exploring between the familiar and novel location or object compared with the L-met group.

Conclusion: This study demonstrates that rosmarinic acid had a protective effect against memory impairment induced by L-met.

References

Miller AL. The methionine-homocysteine cycle and its effects on cognitive diseases. Altern Med Rev 2003;8(1):7-19.

Garlick PJ. Toxicity of methionine in humans. J Nutr 2006;136(6 Suppl):1722s-5s. doi: 10.1093/ jn/136.6.1722S.

Toue S, Kodama R, Amao M, Kawamata Y, Kimura T, Sakai R. Screening of toxicity biomarkers for methionine excess in rats. J Nutr 2006;136(6 Suppl):1716s-21s. doi: 10.1093/jn/136.6.1716S.

de S Moreira D, Figueiró PW, Siebert C, Prezzi CA, Rohden F, Guma FCR, et al. Chronic mild hyperhomocysteinemia alters inflammatory and oxidative/nitrative status and causes protein/DNA damage, as well as ultrastructural changes in cerebral cortex: Is acetylsalicylic acid neuroprotective? Neurotox Res 2018;33(3):580-92. doi: 10.1007/ s12640-017-9847-1.

Hooshmand B, Polvikoski T, Kivipelto M, Tanskanen M, Myllykangas L, Erkinjuntti T, et al. Plasma homocysteine, alzheimer and cerebrovascular pathology: a population-based autopsy study. Brain 2013;136(Pt 9):2707-16. doi: 10.1093/brain/ awt206.

Lazzerini PE, Capecchi PL, Selvi E, Lorenzini S, Bisogno S, Galeazzi M, et al. Hyperhomocysteinemia, inflammation and autoimmunity. Autoimmun Rev 2007;6(7):503-9. doi: 10.1016/j.autrev.2007.03.008.

Moretti R, Giuffré M, Caruso P, Gazzin S, Tiribelli C. Homocysteine in neurology: a possible contributing factor to small vessel disease. Int J Mol Sci 2021;22(4):2051. doi:10.3390/ijms22042051.

Alzoubi KH, Khabour OF, Alfaqih M, Tashtoush M, Al-Azzam SI, Mhaidat NM, et al. The protective effects of pioglitazone against cognitive impairment caused by L-methionine administration in a rat model. CNS Neurol Disord Drug Targets 2022;21(1):77-84. doi: 10.2174/187152732066621 0809122523.

Alzoubi KH, Mhaidat NM, Obaid EA, Khabour OF. Caffeine prevents memory impairment induced by hyperhomocysteinemia. J Mol Neurosci 2018;66(2):222-8. doi: 10.1007/s12031-018-1158-3.

Boldyrev AA. Molecular mechanisms of homocysteine toxicity. Biochemistry (Mosc) 2009;74(6):589-98. doi: 10.1134/s00062979 09060017.

Petersen M, Simmonds MS. Rosmarinic acid. Phytochemistry. 2003;62(2):121-5. doi: 10.1016/ s0031-9422(02)00513-7.

Amoah SK, Sandjo LP, Kratz JM, Biavatti MW. Rosmarinic acid-pharmaceutical and clinical aspects. Planta Med 2016;82(5):388-406. doi: 10.1055/s-0035-1568274.

Hasanein P, Seifi R, Hajinezhad MR, Emamjomeh A. Rosmarinic acid protects against chronic ethanol-induced learning and memory deficits in rats. Nutr Neurosci 2017;20(9):547-54. doi: 10.1080/ 1028415X.2016.1203125.

Farr SA, Niehoff ML, Ceddia MA, Herrlinger KA, Lewis BJ, Feng S, et al. Effect of botanical extracts containing carnosic acid or rosmarinic acid on learning and memory in SAMP8 mice. Physiol Behav 2016;165:328-38. doi: 10.1016/j.physbeh. 2016.08.013.

Cui HY, Zhang XJ, Yang Y, Zhang C, Zhu CH, Miao JY, et al. Rosmarinic acid elicits neuroprotection in ischemic stroke via Nrf2 and heme oxygenase 1 signaling. Neural Regen Res 2018;13(12):2119-28. doi: 10.4103/1673-5374.241463.

Dornlakorn O, Saenno A, Anosri T, Kaewngam S, Suwannakot K. The neuroprotective effect of caffeic acid against L-methionine induced memory deficits in adult rats. Srinagarind Med J 2021;36(5):591-6.

Bhatia P, Singh N. Tadalafil ameliorates memory deficits, oxidative stress, endothelial dysfunction and neuropathological changes in rat model of hyperhomocysteinemia induced vascular dementia. Int J Neurosci 2022;132(4):384-96. doi: 10.1080/00207454.2020.1817009.

Kelley AE. Chapter 19 - locomotor activity and exploration. In: van Haaren F, editor. Techniques in the behavioral and neural sciences 10: Elsevier; 1993:499-518.

Kobayashi K, Shimizu N, Matsushita S, Murata T. The assessment of mouse spontaneous locomotor activity using motion picture. J Pharmacol Sci 2020;143(2):83-8. doi: 10.1016/j.jphs.2020.02.003.

Martínez-Díaz JA, García LI, Hernández ME, Aranda-Abreu GE. Effects on locomotion and memory in 2 models of cerebral hypoperfusion in male Wistar rats. Neurologia 2015;30(7):407-15.

doi: 10.1016/j.nrl.2014.03.001.

Ming GL, Song H. Adult neurogenesis in the mammalian brain: significant answers and significant questions. Neuron 2011;70(4):687-702. doi:10.1016/j.neuron.2011.05.001.

Gibson BM, Mair R. A pathway for spatial memory encoding. Learn Behav 2016;44(2):97-8. doi: 10.3758/s13420-016-0214-5.

Squire LR, Wixted JT, Clark RE. Recognition memory and the medial temporal lobe: a new perspective. Nat Rev Neurosci 2007;8(11):872-83. doi: 10.1038/nrn2154.

Aranarochana A, Kaewngam S, Anosri T, Sirichoat A, Pannangrong W, Wigmore P, et al. Hesperidin reduces memory impairment associated with adult rat hippocampal neurogenesis triggered by valproic acid. Nutrients 2021;13(12):4364. doi: 10.3390/nu13124364.

Sirichoat A, Anosri T, Kaewngam S, Aranarochana A, Pannangrong W, Wigmore P, et al. Neuroprotective properties of chrysin on decreases of cell proliferation, immature neurons and neuronal cell survival in the hippocampal dentate gyrus associated with cognition induced by methotrexate. Neurotoxicology 2022;92:15-24. doi: 10.1016/j. neuro.2022.06.010.

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. doi: 10.1016/j.biopha.2020.110651.

Dix SL, Aggleton JP. Extending the spontaneous preference test of recognition: evidence of object-location and object-context recognition. Behav Brain Res 1999;99(2):191-200. doi: 10.1016/ s0166-4328(98)00079-5.

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(1):15-22. doi: 10.1016/j.neuroscience.2009.

Alzoubi KH, Khabour OF, Al-Azzam SI, Tashtoush MH, Mhaidat NM. Metformin eased cognitive impairment induced by chronic L-methionine administration: potential role of oxidative stress. Curr Neuropharmacol 2014;12(2):186-92. doi:10.2 174/1570159X11666131120223201.

El-Dessouki AM, Galal MA, Awad AS, Zaki HF. Neuroprotective effects of simvastatin and cilostazol in L-methionine-induced vascular dementia in rats. Mol Neurobiol 2017;54(7): 5074-84. doi: 10.1007/s12035-016-0051-8.

Khodir SA, Faried MA, Abd-Elhafiz HI, Sweed EM. Sitagliptin attenuates the cognitive deficits in L-methionine-induced vascular dementia in rats. Biomed Res Int 2022;2022:7222590. doi: 10.1155/ 2022/7222590.

Mangat GS, Jaggi AS, Singh N. Ameliorative effect of a selective endothelin ETA receptor antagonist in rat model of L-methionine-induced vascular dementia. Korean J Physiol Pharmacol 2014;18(3): 201-9. doi: 10.4196/kjpp.2014.18.3.201.

Lipton SA, Kim WK, Choi YB, Kumar S, D'Emilia DM, Rayudu PV, et al. Neurotoxicity associated with dual actions of homocysteine at the N-me¬thyl-D-aspartate receptor. Proc Natl Acad Sci USA 1997;94(11):5923-8. doi: 10.1073/pnas.94.11.5923.

Azzini E, Ruggeri S, Polito A. Homocysteine: its possible emerging role in at-risk population groups. Int J Mol Sci 2020;21(4). doi:10.3390/ ijms21041421.

Noor S, Mohammad T, Rub MA, Raza A, Azum N, Yadav DK, et al. Biomedical features and thera¬peutic potential of rosmarinic acid. Arch Pharm Res 2022;45(4):205-28. doi:10.1007/s12272-022- 01378-2.

Mushtaq N, Schmatz R, Pereira LB, Ahmad M, Stefanello N, Vieira JM, et al. Rosmarinic acid prevents lipid peroxidation and increase in acetylcholinesterase activity in brain of streptozotocin -induced diabetic rats. Cell Biochem Funct 2014;32(3):287-93. doi: 10.1002/cbf.3014.

Flier J, Van Muiswinkel FL, Jongenelen CA, Drukarch B. The neuroprotective antioxidant alpha-lipoic acid induces detoxication enzymes in cultured astroglial cells. Free Radic Res 2002;36(6): 695-9. doi: 10.1080/10715760290029155.

Wei T, Zhao X, Hou J, Ogata K, Sakaue T, Mori A, et al. The antioxidant ESeroS-GS inhibits NO production and prevents oxidative stress in astrocytes. Biochem Pharmacol 2003;66(1):83-91. doi: 10.1016/s0006-2952(03)00231-4.

Downloads

Published

2024-04-24

How to Cite

1.
Chaithum J, Dornlakorn O, Sritawan N, Aranarochana A, Umka Welbat J, Sirichoat A. Beneficial Effect of Rosmarinic Acid on Neurobehavioral Deficits Induced by L-methionine in Adult Rats . SRIMEDJ [Internet]. 2024 Apr. 24 [cited 2024 Nov. 22];39(2):201-8. Available from: https://li01.tci-thaijo.org/index.php/SRIMEDJ/article/view/261477

Issue

Section

Original Articles