동의생리병리학회지 (Journal of Physiology & Pathology in Korean Medicine)

  • 제34권6호
  • /
  • Pages.326-333
  • /
  • 2020
  • /
  • 1738-7698(pISSN)
  • /
  • 2288-2529(eISSN)
대한동의생리학회·한의병리학회 ( The Physiological Society of Korean Medicine and The Society of Pathology in Korean Medicine)
권호 표지
DOI QR코드

DOI QR Code

흰쥐에서 고용량 아질산이온 함유 마늘 발효농축액에 의한 뇌혈류 변화

Changes in Cerebral Blood flow Following Fermented Garlic Extract Solution with High Content of Nitrite

  • 유혁 (원광대학교 의과대학 응급의학교실) ;
  • ;
  • 구호 (원광대학교 산화질소 대사체 연구소 & 의과대학 생리학교실) ;
  • 천현수 ((유)휴먼에노스) ;
  • 유수진 (원광대학교 의과대학 응급의학교실) ;
  • 김민선 (원광대학교 산화질소 대사체 연구소 & 의과대학 생리학교실)
  • Yu, Hyeok (Department of Emergency Medicine, Wonkwang University School of Medicine) ;
  • Rong, Zhang Xiao (Center for Nitric Oxide Metabolite at Wonkwang University & Department of Physiology, Wonkwang University) ;
  • Koo, Ho (Center for Nitric Oxide Metabolite at Wonkwang University & Department of Physiology, Wonkwang University) ;
  • Chun, Hyun Soo (Humanenos Co. LTD) ;
  • Yoo, Su Jin (Department of Emergency Medicine, Wonkwang University School of Medicine) ;
  • Kim, Min Sun (Center for Nitric Oxide Metabolite at Wonkwang University & Department of Physiology, Wonkwang University)
  • 투고 : 2020.09.22
  • 심사 : 2020.10.30
  • 발행 : 2020.12.25
PDF 다운로드
⟨ 이전 논문 다음 논문 ⟩

초록

Nitrate-nitrite-nitric oxide (NO) pathway is a major alternative source of NO and is essential for NO - dependent physiological functions in body. Food supplements having nitrate/nitrite can improve metabolic syndromes including hypertension through antioxidant activity or vasodilation. The purpose of this study was to observe the effects of fermented garlic (F. garlic) having high concentration of NO2- on changes in blood flow and nitric oxide synthesis in the cerebral cortex of rodents. The generation of nitric oxide detected by a chemi-luminescence detector was higher in F. Garlic compared with NaNO2 solution under artificial gastric juice with pH 2.0. Ether F. garlic or NaNO2 diluted with artificial cerebrospinal fluid was directly applied into around the needle probe of laser Doppler flow meter that was located on epidural surface of the cortex. Direct application of F. garlic resulted in increase of cerebral blood flow detected by a laser Doppler flow meter with a dose-dependent manner. Compared with NaNO2 solution, F. garlic produced changes in cerebral blood flow at lower concentration of NO2-. Pretreatment of methylene blue, a guanylyl cyclase inhibitor prevented upregulation of cerebral blood flow by the treatment of F. garlic. In addition, the application of F. garlic with 250, 500ppm of NO2- caused significantly the production of NO in the cortical tissue but NaNO2 solution with 500ppm of NO2- did not. In summary, these results suggested that F. garlic with high content of NO2- induce increase in cerebral blood flow through nitric oxide-dependent signal pathway.

키워드

참고문헌

  1. Bryan NS. Nitric oxide enhancement strategies. Future Sci OA. 2015;1:Fso48. https://doi.org/10.4155/fso.15.48
  2. Bryan NSLefer DJ. Update on Gaseous Signaling Molecules Nitric Oxide and Hydrogen Sulfide: Strategies to Capture their Functional Activity for Human Therapeutics. Mol Pharmacol. 2019;96:109-14. https://doi.org/10.1124/mol.118.113910
  3. Lundberg JO, Gladwin MT, Ahluwalia A, Benjamin N, Bryan NS, et al. Nitrate and nitrite in biology, nutrition and therapeutics. Nat Chem Biol. 2009;5:865-9. https://doi.org/10.1038/nchembio.260
  4. Bryan NS, Fernandez BO, Bauer SM, Garcia-Saura MF, Milsom AB, et al. Nitrite is a signaling molecule and regulator of gene expression in mammalian tissues. Nat Chem Biol. 2005;1:290-7. https://doi.org/10.1038/nchembio734
  5. Blood AB. The Medicinal Chemistry of Nitrite as a Source of Nitric Oxide Signaling. Curr Top Med Chem. 2017;17:1758-68. https://doi.org/10.2174/1568026617666161116145046
  6. Amdahl MBDeMartino AW. Inorganic nitrite bioactivation and role in physiological signaling and therapeutics. 2019;401:201-11. https://doi.org/10.1515/hsz-2019-0349
  7. Carlstrom M, Liu M, Yang T, Zollbrecht C, Huang L, et al. Cross-talk Between Nitrate-Nitrite-NO and NO Synthase Pathways in Control of Vascular NO Homeostasis. Antioxid Redox Signal. 2015;23:295-306. https://doi.org/10.1089/ars.2013.5481
  8. Kina-Tanada M, Sakanashi M, Tanimoto A, Kaname T, Matsuzaki T, et al. Long-term dietary nitrite and nitrate deficiency causes the metabolic syndrome, endothelial dysfunction and cardiovascular death in mice. Diabetologia. 2017;60:1138-51. https://doi.org/10.1007/s00125-017-4259-6
  9. Chun HS. Manufacturing methods of natural fermented products containing nitric oxide metabolites and composites of their products . 2016: Korea. p. 10.
  10. Chun HS. Manufacturing method of fixation and stabilization of nitric oxide metabolites through fermentation of natural products having nitrogen. 2019: Korea. p. 18.
  11. Ginter ESimko V. Garlic (Allium sativum L.) and cardiovascular diseases. Bratisl Lek Listy. 2010;111:452-6.
  12. Rana SV, Pal R, Vaiphei K, Sharma SKOla RP. Garlic in health and disease. Nutr Res Rev. 2011;24:60-71. https://doi.org/10.1017/S0954422410000338
  13. Imai J, Ide N, Nagae S, Moriguchi T, Matsuura H, et al. Antioxidant and radical scavenging effects of aged garlic extract and its constituents. Planta Med. 1994;60:417-20. https://doi.org/10.1055/s-2006-959522
  14. Park BM, Chun H, Chae SWKim SH. Fermented garlic extract ameliorates monocrotaline-induced pulmonary hypertension in rats. Journal of Functional Foods. 2017;30:7.
  15. Lee YJ, Lee D, Shin SM, Lee JS, Chun HS, 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.
  16. Park BM, Cha SA, Kim HY, Kang DK, Yua K, 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.
  17. Shin JH. Metzger SKSchoenfisch MH. Synthesis of nitric oxide-releasing silica nanoparticles. J Am Chem Soc. 2007;129:4612-9. https://doi.org/10.1021/ja0674338
  18. Park BM, Kim MS, Yee GH, Moon MJ, Kim HJ, et al. Changes in Vestibular Nerve Activity Following Acute Hypotension in Rats. Korean J Physiol Pharmacol. 2003;7:5.
  19. Soares de Moura RS, Leão MC, Castro Resende AC, Moreira CF, Sena KM, et al. Actions of L-NAME and methylene blue on the hypotensive effects of clonidine and rilmenidine in the anesthetized rat. J Cardiovasc Pharmacol. 2000;35:791-5. https://doi.org/10.1097/00005344-200005000-00017
  20. Münzel TDaiber A. Inorganic nitrite and nitrate in cardiovascular therapy: A better alternative to organic nitrates as nitric oxide donors? Vascul Pharmacol. 2018;102:1-10. https://doi.org/10.1016/j.vph.2017.11.003
  21. Gori T. Exogenous NO Therapy for the Treatment and Prevention of Atherosclerosis. Int J Mol Sci. 2020;21.
  22. Pluta RM, Oldfield EH, Bakhtian KD, Fathi AR, Smith RK, et al. Safety and feasibility of long-term intravenous sodium nitrite infusion in healthy volunteers. PLoS One. 2011;6:e14504. https://doi.org/10.1371/journal.pone.0014504
  23. Dejam A, Hunter CJ, Tremonti C, Pluta RM, Hon YY, et al. Nitrite infusion in humans and nonhuman primates: endocrine effects, pharmacokinetics, and tolerance formation. Circulation. 2007;116:1821-31. https://doi.org/10.1161/CIRCULATIONAHA.107.712133
  24. Maia LBMoura JJ. Nitrite reduction by molybdoenzymes: a new class of nitric oxide-forming nitrite reductases. J Biol Inorg Chem. 2015;20:403-33. https://doi.org/10.1007/s00775-014-1234-2
  25. Bryan NS, Alexander DD, Coughlin JR, Milkowski ALBoffetta P. Ingested nitrate and nitrite and stomach cancer risk: an updated review. Food Chem Toxicol. 2012;50:3646-65. https://doi.org/10.1016/j.fct.2012.07.062
  26. Uray T, Empey PE, Drabek T, Stezoski JP, Janesko-Feldman K, et al. Nitrite pharmacokinetics, safety and efficacy after experimental ventricular fibrillation cardiac arrest. Nitric Oxide. 2019;93:71-7. https://doi.org/10.1016/j.niox.2019.09.003
  27. Dezfulian C, Kenny E, Lamade A, Misse A, Krehel N, et al. Mechanistic characterization of nitrite-mediated neuroprotection after experimental cardiac arrest. Journal of neurochemistry. 2016;139:419-31. https://doi.org/10.1111/jnc.13764
  28. d'Ischia M, Napolitano A, Manini PPanzella L. Secondary targets of nitrite-derived reactive nitrogen species: nitrosation/nitration pathways, antioxidant defense mechanisms and toxicological implications. Chem Res Toxicol. 2011;24:2071-92. https://doi.org/10.1021/tx2003118
  29. Ried K, Fakler P. Potential of garlic (Allium sativum) in lowering high blood pressure: mechanisms of action and clinical relevance. Integr Blood Press Control. 2014;7:71-82. https://doi.org/10.2147/IBPC.S51434
  30. Fahim MAEl-Sabban FF. Garlic prevents ultrastructural alterations caused by dehydration in mouse cerebral microvessels. Anat Rec. 2001;263:85-90. https://doi.org/10.1002/ar.1080
  31. Sueishi Y, Hori M, Kita MKotake Y. Nitric oxide (NO) scavenging capacity of natural antioxidants. Food Chem. 2011;129:866-70. https://doi.org/10.1016/j.foodchem.2011.05.036
  32. Takahama UHirota S. Possible Reactions of Dietary Phenolic Compounds with Salivary Nitrite and Thiocyanate in the Stomach. Antioxidants (Basel). 2017;6.
  33. Suzuki A, Yamamoto M, Jokura H, Fujii A, Tokimitsu I, et al. Ferulic acid restores endothelium-dependent vasodilation in aortas of spontaneously hypertensive rats. Am J Hypertens. 2007;20:508-13. https://doi.org/10.1016/j.amjhyper.2006.11.008