대한약침학회지 (Journal of Pharmacopuncture)

  • 제19권4호
  • /
  • Pages.329-335
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  • 2016
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  • 2093-6966(pISSN)
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  • 2234-6856(eISSN)
대한약침학회 (KOREAN PHARMACOPUNCTURE INSTITUTE)
권호 표지
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The Relaxant Activity of Safranal in Isolated Rat Aortas is Mediated Predominantly via an Endothelium-Independent Mechanism - Vasodilatory mechanism of safranal -

  • Razavi, Bibi Marjan (Targeted Drug Delivery Research Center, Department of Pharmacodynamics and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences) ;
  • Amanloo, Mojtaba Alipoor (School of Pharmacy, Mashhad University of Medical Sciences) ;
  • Imenshahidi, Mohsen (Pharmaceutical Research Center, Department of Pharmacodynamy and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences) ;
  • Hosseinzadeh, Hossein (Pharmaceutical Research Center, Department of Pharmacodynamy and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences)
  • 투고 : 2016.08.03
  • 심사 : 2016.08.30
  • 발행 : 2016.12.31
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초록

Objectives: Safranal is a pharmacologically active component of saffron and is responsible for the unique aroma of saffron. The hypotensive effect of safranal has been shown in previous studies. This study evaluates the mechanism for the vasodilatory effects induced by safranal on isolated rat aortas. Methods: To study the vasodilatory effects of safranal (0.2, 0.4 and 0.8 mM), we contracted isolated rat thoracic aorta rings by using $10^{-6}-M$ phenylephrine (PE) or 80-mM KCl. Dimethyl sulfoxide (DMSO) was used as a control. The vasodilatory effect of safranal was also evaluated both on intact and denuded endothelium aortic rings. Furthermore, to study the role of nitric oxide and prostacyclin in the relaxation induced by safranal, we incubated the aortic rings by using L-NAME ($10^{-6}M$) or indomethacin ($10^{-5}M$), each for 20 minutes. Results: Safranal induced relaxation in endothelium-intact aortic rings precontracted by using PE or KCl in a concentration-dependent manner, with a maximum relaxation of more than 100%. The relaxant activity of safranal was not eliminated by incubating the aortic rings with L-NAME ($EC_{50}=0.29$ vs. $EC_{50}=0.43$) or with indomethacin ($EC_{50}=0.29$ vs. $EC_{50}=0.35$), where $EC_{50}$ is the half maximal effective concentration. Also, the vasodilatory activity of safranal was not modified by endothelial removal. Conclusion: This study indicated that relaxant activity of safranal is mediated predominantly through an endothelium-independent mechanism.

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참고문헌

  1. Sandoo A, Veldhuijzen van Zanten JCS, Metsios GS, Carroll D, Kitas GD. The endothelium and its role in regulating vascular tone. Open Cardiovasc Med J. 2010;4:302-12. https://doi.org/10.2174/1874192401004010302
  2. Dharmashankar K, Widlansky ME. Vascular endothelial function and hypertension: insights and directions. Curr Hypertens Rep. 2010;12(6):448-55. https://doi.org/10.1007/s11906-010-0150-2
  3. MA, Alhamdan AA, Pugalendi KV. Antihypertensive effect of Melothria maderaspatana leaf fractions on DOCA-salt-induced hypertensive rats and identification of compounds by GC-MS analysis. J Nat Med. 2012;66(2):302-10. https://doi.org/10.1007/s11418-011-0590-2
  4. Krum H, Pellizzer AM. New and emerging drug treatments for hypertension. Aust Fam Physician. 1998;27(4):235-7.
  5. Talha J, Priyanka M, Akanksha A. Hypertension and herbal plants. Int Res J Pharm. 2011;2(8):26-30.
  6. Hosseinzadeh H, Nassiri-Asl M. Avicenna's (Ibn Sina) the canon of medicine and saffron (Crocus sativus): a review. Phytother Res. 2013;27(4):475-83. https://doi.org/10.1002/ptr.4784
  7. Hosseinzadeh H, Khosravan V. Anticonvulsant effects of aqueous and ethanolic extracts of Crocus sativus L. stigmas in mice. Arch Iran Med. 2002;5:44-7.
  8. Hosseinzadeh H, Karimi G, Niapoor M. Antidepressant effect of Crocus sativus L. Stigma extracts and their constituents, crocin and safranal, in Mice. J Med Plants. 2004;3:48-58.
  9. Vahdati Hassani F, Naseri V, Razavi BM, Mehri S, Ab-nous K, Hosseinzadeh H. Antidepressant effects of crocin and its effects on transcript and protein levels of CREB, BDNF, and VGF in rat hippocampus. DARU. 2014;22(1):DOI: 10.1186/2008-2231-22-16.
  10. Ghasemi T, Abnous K, Vahdati F, Mehri S, Razavi BM, Hosseinzadeh H. Antidepressant effect of Crocus sati-vus aqueous extract and its effect on CREB, BDNF, and VGF transcript and protein levels in rat hippocampus. Drug Res. 2015;65(7):337-43. https://doi.org/10.1055/s-0034-1371876
  11. Hosseinzadeh H,Younesi HM. Antinociceptive and an-ti-inflammatory effects of Crocus sativus L. stigma and petal extracts in mice. BMC Pharmacol. 2002;2:DOI: 10.1186/1471-2210-2-7.
  12. Hosseinzadeh H, Shamsaie F, Mehri S. Antioxidant activity of aqueous and ethanolic extracts of Crocus sati-vus L. stigma and its bioactive constituents crocin and safranal. Pharmacogn Mag. 2010;5(20):419-24.
  13. Abdullaev FI. Biological effects of saffron. Biofactors. 1993;4(2):83-6.
  14. Hosseinzadeh H, Behravan J, Ramezani M, Ajgan KH. Anti-tumor and cytotoxic evaluation of Crocus sativus L. stigma and petal extracts using brine shrimp and potato disc assays. J Med Plants. 2005;4(15):59-65.
  15. Imenshahidi M, Hosseinzadeh H, Javadpour Y. Hypo-tensive effect of aqueous saffron extract (Crocus sa-tivus L.) and its constituents, safranal and crocin, in normotensive and hypertensive rats. Phytother Res. 2010;24(7):990-4. https://doi.org/10.1002/ptr.3044
  16. Imenshahidi M, Razavi BM, Faal A, Gholampoor A, Mousavi SM, Hosseinzadeh H. Effects of chronic crocin treatment on desoxycorticosterone acetate (doca)-salt hypertensive rats. Iran J Basic Med Sci. 2014;17(1):9-13.
  17. Razavi BM, Hosseinzadeh H. Saffron as an antidote or a protective agent against natural or chemical toxicities. DARU. 2015;23:DOI: 10.1186/s40199-015-0112-y.
  18. Bathaie SZ, Mousavi SZ. New applications and mechanisms of action of saffron and its important ingredients. Crit Rev Food Sci Nutr. 2010;50(8):761-86. https://doi.org/10.1080/10408390902773003
  19. Alavizadeh SH, Hosseinzadeh H. Bioactivity assessment and toxicity of crocin: a comprehensive review. Food Chem Toxicol. 2014;64:65-80. https://doi.org/10.1016/j.fct.2013.11.016
  20. Rezaee R, Hosseinzadeh H. Safranal: from an aromatic natural product to a rewarding pharmacological agent. Iran J Basic Med Sci. 2013;16(1):12-26.
  21. Assimopoulou AN, Sinakos Z, Papageorgiou VP. Radical scavenging activity of Crocus sativus L. extract and its bioactive constituents. Phytother Res. 2005;19(11):997-1000. https://doi.org/10.1002/ptr.1749
  22. Hosseinzadeh H, Talebzadeh F. Anticonvulsant evaluation of safranal and crocin from Crocus sativus in mice. Fitoterapia.2005;76(7-8):722-4. https://doi.org/10.1016/j.fitote.2005.07.008
  23. Nemati H, Boskabady MH, Ahmadzadeh Vostakolaei H. Stimulatory effect of Crocus sativus (saffron) on ${\beta}2$-adrenoreceptors of guinea pig tracheal chains. Phy-tomedicine. 2008;15(12):1038-45.
  24. Amin B, Hosseinzadeh H. Evaluation of aqueous and ethanolic extracts of saffron, Crocus sativus L. and its constituents, safranal and crocin in allodynia and hyperalgesia induced by chronic constriction in-jury model of neuropathic pain in rats. Fitoterapia. 2012;83(5):888-95. https://doi.org/10.1016/j.fitote.2012.03.022
  25. Hosseinzadeh H, Sadeghnia H. Safranal, a constituent of Crocus sativus (saffron), attenuated cerebral is-chemia induced oxidative damage in rat hippocampus. J Pharm Pharm Sci. 2005;8(3):394-9.
  26. Hosseinzadeh H, Ziaei T. Effects of Crocus sativus stigma extract and its constituents, crocin and safranal, on intact memory and scopolamine-induced learning deficits in rats performing the Morris water maze task. J Med Plants. 2006;5:40-50.
  27. Boskabady MH, Shafei MN, Shakiba A, Sefidi HS. Ef-fect of aqueous-ethanol extract from Crocus sativus (saffron) on guinea-pig isolated heart. Phytother Res. 2008;22(3):330-4. https://doi.org/10.1002/ptr.2317
  28. Mehdizadeh R, Parizadeh MR, Khooei AR, Mehri S, Hosseinzadeh H. Cardioprotective effect of saffron extract and safranal in isoproterenol-induced myocardial infarction in wistar rats. Iran J Basic Med Sci. 2013;16(1):56-63.
  29. Imenshahidi M, Razavi BM, Faal A, Gholampoor A, Mousavi SM, Hosseinzadeh H. The effect of chronic administration of safranal on systolic blood pressure in rats. Iran J Pharm Res. 2015;14(2):585-90.
  30. Parsaee H, Imenshahidi M, Fatehi Z. Lovastatin incubation improves acetylcholine-induced relaxation in isolated aortic rings of diabetic rat. Iran J Pharm Res. 2006;5(3):191-8.
  31. Boskabady MH, Aslani MR. Relaxant effect of Crocus sativus (saffron) on guinea pig tracheal chains and its possible mechanisms. J Pharm Pharmacol. 2006;58(10):1385-90. https://doi.org/10.1211/jpp.58.10.0012
  32. Mombouli JV, Vanhoutte PM. Endothelial dysfunction: from physiology to therapy. J Mol Cell Cardiol. 1999;31(1):61-74. https://doi.org/10.1006/jmcc.1998.0844
  33. Dehpour AR, Ghafourifar P, Samenian J, Sadeghipour HR, Sadr SS. The effect of lithium on endothelial-de-pendent relaxation in rat isolated aorta. Gen Pharma-col. 1995;26(5):1003-7. https://doi.org/10.1016/0306-3623(94)00286-V
  34. Sausbier M, Schubert R, Voigt V, Hirneiss C, Pfeifer A, Korth M, et al. Mechanisms of NO/cGMP-dependent vasorelaxation. Circ Res. 2000;87(9):825-30. https://doi.org/10.1161/01.RES.87.9.825
  35. Mashhoodi T, Zahedi-Asl S, Sarkaki A. Inhibitory effect of aluminium on KCl and phenylephrine induced contraction in isolated rat aorta. Acta Medica Iranica. 2004;42(5):379-82.
  36. Nugent M, Artru A, Michenfclder JD. Cerebral metabolic vascular and protective effects of midazolam maleate: comparison to diazepam. Anesthesiology. 1982;56(3):172-6. https://doi.org/10.1097/00000542-198203000-00003
  37. Hosseinzadeh H, Sadeghi Shakib S, Khadem Sameni A, Taghiabadi E. Acute and subacute toxicity of safranal, a constituent of saffron, in mice and rats. Iran J Pharm Res. 2013;12(1):93-9.