Journal of Physiology & Pathology in Korean Medicine (동의생리병리학회지)

The Physiological Society of Korean Medicine and The Society of Pathology in Korean Medicine (대한동의생리학회·한의병리학회)
권호 표지
DOI QR코드

DOI QR Code

Effect of Fermented Garlic Extract Containing Nitric Oxide Metabolites on Impairments of Memory and of Neural Plasticity in Rat Model of Vascular Dementia

산화질소 대사체 함유 마늘 발효 추출물 이용 혈관성 치매 흰쥐 모델의 기억력 및 신경가소성 장애 개선 효과

  • Zhang, Xiaorong (Department of Physiology, School of Medicine, Wonkwang University) ;
  • Moon, Se Jin (Department of Physiology, School of Medicine, Wonkwang University) ;
  • Kim, Yoo Ji (Department of Physiology, School of Medicine, Wonkwang University) ;
  • Jeong, Sun Oh (Department of Physiology, School of Medicine, Wonkwang University) ;
  • Kim, Min Sun (Department of Physiology, School of Medicine, Wonkwang University)
  • 장소영 (원광대학교 의과대학 생리학교실) ;
  • 문세진 (원광대학교 의과대학 생리학교실) ;
  • 김유지 (원광대학교 의과대학 생리학교실) ;
  • 정선오 (원광대학교 의과대학 생리학교실) ;
  • 김민선 (원광대학교 의과대학 생리학교실)
  • Received : 2022.03.23
  • Accepted : 2022.04.25
  • Published : 2022.04.25
Download PDF
⟨ Previous Next ⟩

Abstract

Rodent model for chronic cerebral hypoperfusion caused by bilateral carotid artery occlusion (BCAO) show clinically relevant evidences for vascular dementia and impairments of synaptic plasticity in the hippocampus. The purpose of this study was to evaluate effect of fermented garlic (F-Garlic) extract with NO metabolites on cognitive behaviors, synaptic plasticity, and molecular events in the hippocampus following BCAO. Adult male Sprague-Dawley rats were randomly divided three experimental groups into: control+water; BCAO+water; BCAO+F-Garlic. Animals were treated with oral administration of F-Garlic in tap water as a drinking water after surgery for 4 weeks. On passive avoidance test and Y-maze test, BCAO+water showed a significant decrease in step-through latency and spontaneous alteration, indicating deficit of hippocampal memory formation but the treatment of F-Garlic significantly increased these cognitive behaviors. In control+water, a robust increase in the amplitude of evoked field excitatory postsynaptic potentials was observed by theta burst stimulation to hippocampal neural circuit indicating formation of long-term potentiation (LTP) in the hippocampal CA1. BCAO+water showed a highly significant deficit in LTP induction 4 weeks after BCAO. On other hand, daily oral administration of F-Garlic extract caused the marked preservation of LTP induction. Moreover, parvalbumin was markedly reduced in the CA1, especially, in the stratum radiatum of BCAO+water. In contrast, BCAO+F-Garlic mitigate a significantly reduction of the parvalbumin. In summary, these results suggest that daily oral administration of F-Garlic extract can ameliorate cognitive memory deficit through the preservation of synaptic plasticity and interneurons integrity in the hippocampus in rodent model of chronic cerebral hypoperfusion.

Keywords

Acknowledgement

이 논문은 2021년도 완주군 지역자원특화사업단의 지원을 받아 수행된 향토산업육성사업임

References

  1. Tsuda Y, Yamada K, Hayakawa T, Ayada Y, Kawasaki S, Matsuo H. Cortical blood flow and cognition after extracranial-intracranial bypass in a patient with severe carotid occlusive lesions. A three-year follow-up study. Acta neurochirurgica. 1994;129(3-4):198-204. https://doi.org/10.1007/BF01406505
  2. Farkas E, Luiten PG, Bari F. Permanent, bilateral common carotid artery occlusion in the rat: a model for chronic cerebral hypoperfusion-related neurodegenerative diseases. Brain research reviews. 2007;54(1):162-80. https://doi.org/10.1016/j.brainresrev.2007.01.003
  3. Bryan NS. Nitric oxide enhancement strategies. Future science OA. 2015;1(1):Fso48. https://doi.org/10.4155/fso.15.48
  4. Amdahl MB, DeMartino AW. Inorganic nitrite bioactivation and role in physiological signaling and therapeutics. 2019;401(1):201-11. https://doi.org/10.1515/hsz-2019-0349
  5. Son O, Seo BI, Lee SH, Park SJ. The Study of DNA markers to identify of Allium sativum L. Kor J Herbology. 2014;29:7.
  6. Ginter E, Simko V. Garlic (Allium sativum L.) and cardiovascular diseases. Bratislavske lekarske listy. 2010;111(8):452-6.
  7. Chun HS. Manufacturing method of fermented garlic composition and the fermented garlic composition thereof. IPC A23L 1/212 C12P 1/04, AN 1020140048259, 2014. 4.22, Republic of Korea. 2014.
  8. Baluchnejadmojarad T, Kiasalari Z, Afshin-Majd S, Ghasemi Z, Roghani M. S-allyl cysteine ameliorates cognitive deficits in streptozotocin-diabetic rats via suppression of oxidative stress, inflammation, and acetylcholinesterase. European journal of pharmacology. 2017;794:69-76. https://doi.org/10.1016/j.ejphar.2016.11.033
  9. Park BM, Cha SA, Kim HY, Kang DK, Yua K, Chun H, et al. Fermented garlic extract decreases blood pressure through nitrite and sGC-cGMP-PKG pathway in spontaneously hypertensive rats. Journal of Functional Foods. 2016;22:10.
  10. Yu H, Rong ZX, Koo H, Chun HS, Yoo SJ, Kim MS. Changes in Cerebral Blood flow Following Fermented Garlic Extract Solution with High Content of Nitrite. The Physiological Society of Korean Medicine and The Society of Pathology in Korean Medicine 2020:8.
  11. Mun CH, Lee WT, Park KA, Lee JE. Regulation of endothelial nitric oxide synthase by agmatine after transient global cerebral ischemia in rat brain. Anatomy & cell biology. 2010;43(3):230-40. https://doi.org/10.5115/acb.2010.43.3.230
  12. Bryan NS, Fernandez BO, Bauer SM, Garcia-Saura MF, Milsom AB, Rassaf T, et al. Nitrite is a signaling molecule and regulator of gene expression in mammalian tissues. Nature chemical biology. 2005;1(5):290-7. https://doi.org/10.1038/nchembio734
  13. Wightman EL, Haskell-Ramsay CF, Thompson KG, Blackwell JR, Winyard PG, Forster J, et al. Dietary nitrate modulates cerebral blood flow parameters and cognitive performance in humans: A double-blind, placebo-controlled, crossover investigation. Physiology & Behavior. 2015;149:149-58. https://doi.org/10.1016/j.physbeh.2015.05.035
  14. Cimadevilla JM, Mendez-Lopez M, Mendez M, Arias JL. Interhippocampal transfer in passive avoidance task modifies metabolic activity in limbic structures. Hippocampus. 2011;21(1):48-55. https://doi.org/10.1002/hipo.20720
  15. Xiong Z, Liu C, Wang F, Li C, Wang W, Wang J, et al. Protective effects of breviscapine on ischemic vascular dementia in rats. Biological & pharmaceutical bulletin. 2006;29(9):1880-5. https://doi.org/10.1248/bpb.29.1880
  16. Whitlock JR, Heynen AJ, Shuler MG, Bear MF. Learning induces long-term potentiation in the hippocampus. Science (New York, NY). 2006;313(5790):1093-7. https://doi.org/10.1126/science.1128134
  17. Kim DH, Kim JM, Park SJ, Lee S, Shin CY, Cheong JH, et al. Hippocampal extracellular signal-regulated kinase signaling has a role in passive avoidance memory retrieval induced by GABAA Receptor modulation in mice. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology. 2012;37(5):1234-44. https://doi.org/10.1038/npp.2011.311
  18. Luo P, Lu Y, Li C, Zhou M, Chen C, Lu Q, et al. Long-lasting spatial learning and memory impairments caused by chronic cerebral hypoperfusion associate with a dynamic change of HCN1/HCN2 expression in hippocampal CA1 region. Neurobiology of learning and memory. 2015;123:72-83. https://doi.org/10.1016/j.nlm.2015.05.005
  19. Zhuo M, Hu Y, Schultz C, Kandel ER, Hawkins RD. Role of guanylyl cyclase and cGMP-dependent protein kinase in long-term potentiation. Nature. 1994;368(6472):635-9. https://doi.org/10.1038/368635a0
  20. Nelissen E, Possemis N, Van Goethem NP, Schepers M, Mulder-Jongen DAJ, Dietz L, et al. The sGC stimulator BAY-747 and activator runcaciguat can enhance memory in vivo via differential hippocampal plasticity mechanisms. Scientific reports. 2022;12(1):3589. https://doi.org/10.1038/s41598-022-07391-1
  21. Correia SS, Iyengar RR, Germano P, Tang K, Bernier SG, Schwartzkopf CD, et al. The CNS-Penetrant Soluble Guanylate Cyclase Stimulator CY6463 Reveals its Therapeutic Potential in Neurodegenerative Diseases. Frontiers in pharmacology. 2021;12:656561. https://doi.org/10.3389/fphar.2021.656561
  22. Zhang H, Sun XR, Wang J, Zhang ZZ, Zhao HT, Li HH, et al. Reactive Oxygen Species-mediated Loss of Phenotype of Parvalbumin Interneurons Contributes to Long-term Cognitive Impairments After Repeated Neonatal Ketamine Exposures. Neurotoxicity research. 2016;30(4):593-605. https://doi.org/10.1007/s12640-016-9653-1
  23. Lee YJ, Lee D, Shin SM, Lee JS, Chun HS, Quan FS, et al. Potential protective effects of fermented garlic extract on myocardial ischemia-reperfusion injury utilizing in vitro and ex vivo models. Journal of Functional Foods. 2017;33:8.
  24. Carlstrom M, Montenegro MF. Therapeutic value of stimulating the nitrate-nitrite-nitric oxide pathway to attenuate oxidative stress and restore nitric oxide bioavailability in cardiorenal disease. 2019;285(1):2-18. https://doi.org/10.1111/joim.12818
  25. Dezfulian C, Kenny E, Lamade A, Misse A, Krehel N, St Croix C, et al. Mechanistic characterization of nitrite-mediated neuroprotection after experimental cardiac arrest. J Neurochem. 2016;139(3):419-31. https://doi.org/10.1111/jnc.13764