Oroxylin-A and its phosphonate derivative potentiate eNOS/NO-mediated relaxation and attenuate vasoconstrictor-induced contraction in the mouse aorta

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標題:	Oroxylin-A and its phosphonate derivative potentiate eNOS/NO-mediated relaxation and attenuate vasoconstrictor-induced contraction in the mouse aorta
作者:	Tseng, Tzu-Ling Ho, Wen-Yueh Huang, Po-Jui Liao, Jin-Zhi Lee, Kuan-Han
貢獻者:	Buddhist Tzu Chi General Hospital Hualien Tzu Chi Hospital Tzu Chi University of Science & Technology Chia Nan University of Pharmacy & Science Kaohsiung Medical University Department of Cosmetic Science, Chia Nan University of Pharmacy & Science Departments of Medicinal Chemistry, Chia Nan University of Pharmacy & Science Departmentof Pharmacy, Chia Nan University of Pharmacy & Science
關鍵字:	nitric-oxide memory impairment channels inhibition flavonoids
日期:	2022
上傳時間:	2023-12-11 14:01:55 (UTC+8)
出版者:	JAPANESE PHARMACOLOGICAL SOC
摘要:	Oroxylin-A (OroA), a flavonoid isolated from Scutellariae baicalensis, alleviates cardiovascular dysfunction. Several procedures for synthesizing OroA have been developed but show low production yield and regioselectivity. We synthesized OroA from baicalin using a one-pot reaction to increase its overall yield. We also determined the chemical properties and mechanism of action of the synthesized OroA and OroA phosphate diethyl ester (OroA-OET) in vascular function. The induction of vascular reactivity by OroA and OroA-OET was evaluated using blood vessel myography and biochemical analysis to assess nitric oxide synthase-mediated nitric oxide production in mouse aortic arteries. OroA and OroA-OET (0.1-30 mM) induced sustained vasorelaxation, which was partly mediated by the endothelium in isolated normal arteries pre-contracted with phenylephrine. OroA and OroA-OET significantly attenuated vasoconstrictors-induced contractile responses. Dilation effects were blocked by the non-selective nitric oxide synthase inhibitor N (omega)-nitro-L-arginine methyl ester but not by tetraethylammonium or 1H(1,2,4)oxadiazolo [4,3-a]quinoxalin-1-one. Notably, preincubation with OroA and OroA-OET potentiated acetylcholine-induced relaxation and endothelial nitric oxide production in the arteries with the endothelium. OroA and OroA-OET protected against cardiovascular dysfunction. The synthesis and lead compounds used not only improved the yield of OroA from natural sources but also potentially regulated vascular tone.(c) 2022 The Authors. Production and hosting by Elsevier B.V. on behalf of Japanese Pharmacological Society. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/ licenses/by-nc-nd/4.0/).
關聯:	JOURNAL OF PHARMACOLOGICAL SCIENCES, v.150, Issue 4, pp.223-232
顯示於類別:	[化妝品應用與管理系(所)] 期刊論文 [藥學系(所)] 期刊論文

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