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一氧化氮在日本水杨梅提取物及纯化单宁的血管舒张和降压作用中的作用

Role of nitric oxide in the vasorelaxant and hypotensive effects of extracts and purified tannins from Geum japonicum.

作者信息

Xie Yi-Wu, Xu Hong-Xi, Dong Hui, Fiscus Ronald R, But Paul P H

机构信息

Department of Biology, The Chinese University of Hong Kong, Shatin, Hong Kong, China.

出版信息

J Ethnopharmacol. 2007 Jan 3;109(1):128-33. doi: 10.1016/j.jep.2006.07.015. Epub 2006 Jul 21.

Abstract

Crude extracts and three purified tannins from Geum japonicum Thunberg (Rosaceae) were examined for relaxant effects in isolated rat thoracic aorta and for hypotensive effects in anesthetized normotensive and hypertensive rats. The acetone extract and the butyl alcohol extract of Geum japonicum at a cumulative concentration of 30mug/ml potently relaxed phenylephrine-precontracted aortic rings by 73+/-5% and 80+/-7%, respectively, without affecting the resting tension of these vessels. Removal of the vascular endothelium, inhibition of nitric oxide (NO) synthase with N(omega)-nitro-l-arginine (l-NA) or inhibition of cGMP biosynthesis with methylene blue all abolished the vasorelaxant effects of the Geum japonicum extracts. Addition of l-arginine, the substrate for NO biosynthesis, reversed the inhibitory effects of l-NA. Similar vasorelaxant effects of 82+/-10%, 61+/-8% and 82+/-14%, were observed with the purified tannins, penta-O-galloyl-beta-glucoside, casuariin and 5-desgalloylstachyurin, respectively, at a cumulative concentration of 10muM. Intravenous injection of the butyl alcohol extract of Geum japonicum at a cumulative dose of 2.5mg/kg into both hypertensive and normotensive rats resulted in a marked reduction in the mean arterial blood pressure by 46+/-6% and 34+/-7%, respectively, which was abolished by prior injection of l-NA. Therefore, these results suggest that tannins may be responsible for the vasorelaxant and hypotensive effects of Geum japonicum, mediated via endogenous NO and subsequent cGMP formation. The data suggest that extracts of Geum japonicum may have potential use as new anti-hypertensive agents for lowering arterial blood pressure in hypertensive patients.

摘要

研究了水杨梅(蔷薇科)的粗提物和三种纯化单宁对离体大鼠胸主动脉的舒张作用以及对麻醉的正常血压和高血压大鼠的降压作用。水杨梅的丙酮提取物和正丁醇提取物在累积浓度为30μg/ml时,能有效舒张苯肾上腺素预收缩的主动脉环,分别达到73±5%和80±7%,且不影响这些血管的静息张力。去除血管内皮、用N(ω)-硝基-L-精氨酸(L-NA)抑制一氧化氮(NO)合酶或用亚甲蓝抑制cGMP生物合成均能消除水杨梅提取物的血管舒张作用。添加L-精氨酸(NO生物合成的底物)可逆转L-NA的抑制作用。在累积浓度为10μM时,纯化单宁五-O-没食子酰-β-葡萄糖苷、木麻黄鞣质和5-去没食子酰原花青素分别产生了类似的血管舒张作用,分别为82±10%、61±8%和82±14%。向高血压和正常血压大鼠静脉注射累积剂量为2.5mg/kg的水杨梅正丁醇提取物,平均动脉血压分别显著降低46±6%和34±7%,预先注射L-NA可消除该作用。因此,这些结果表明,单宁可能是水杨梅血管舒张和降压作用的原因,其作用是通过内源性NO和随后的cGMP形成介导的。数据表明,水杨梅提取物可能有潜力作为新型抗高血压药物用于降低高血压患者的动脉血压。

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