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旋覆花甲醇提取物的降压和血管舒张作用:紫锥菊苷、绿原酸作为潜在降压物质的生物评价和 POM 分析

Antihypertensive and vasodilator effects of methanolic extract of Inula viscosa: Biological evaluation and POM analysis of cynarin, chlorogenic acid as potential hypertensive.

机构信息

Laboratoire de Physiologie et Ethnopharmacologie URAC40, Faculté des Sciences, Université Mohammed Premier, Oujda, Morocco.

Laboratoire de Pharmacognosie UPRES-A 8076 CNRS, BIOCIS, Faculté de Pharmacie Université Paris Sud XI Chatenay Malabry, France.

出版信息

Biomed Pharmacother. 2017 Sep;93:62-69. doi: 10.1016/j.biopha.2017.06.015. Epub 2017 Jun 15.

Abstract

BACKGROUND

Inula viscosa L. (Asteraceae) is a medicinal plant widely used as a folk medicine in oriental Morocco, to treat hypertension. The antihypertensive effect of the methanolic extract obtained from I. viscosa leaves was evaluated in hypertensive L-NAME rats. Systolic blood pressure (SBP) was measured using a non-invasive indirect tail-cuff plethysmographic method. Four groups of rats were used: a control group; a hypertensive group treated with L-NAME (32mg/kg/day); a positive control group treated with L-NAME plus enalapril (15mg/kg/day) as a reference antihypertensive agent; and a group treated with L-NAME plus MeOH-extract (40mg/kg/day).

METHODS

Treatment with L-NAME alone caused a progressive increase in SBP. After 4 weeks, the value of SBP reached 160±2mmHg which shows the installation of hypertension. Enalapril prevented the increase in SBP, which remained normal at 123±1mmHg after 4 weeks of treatment. The administration of MeOH-extract along with L-NAME prevented the increase in SBP as well, which remained constant at 115±1mmHg after 4 weeks of treatment. In ex-vivo models, MeOH-extract produced a relaxation of pre-contracted ring aorta (54 ± 2% of relaxation at 3g/L). But, when the rings were denuded, MeOH-extract failed to relax pre-contracted rings of aorta. Phytochemical study of I. viscosa MeOH-extract revealed the presence of phenolic compounds, such as cynarin and chlorogenic acid.

RESULTS

The present results suggest that I. viscosa MeOH-extract has an antihypertensive, predominantly mediated by an endothelium-dependent vasodilatory effect. Cynarin and chlorogenic acid, which have a strong vasorelaxant effect may be involved in the antihypertensive effect of the plant extract. The bioinformatic POM analysis confirms the therapeutic potential of cynarin and chlorogenic acids as inhibitors of various biotargets. Based on the results, the coordination of these phytochemicals with calcium and transition metals should be studied, for better scope at antihypertensive drug development.

摘要

背景

旋覆花(菊科)是一种药用植物,在摩洛哥东部被广泛用作民间药物,用于治疗高血压。本文评估了旋覆花叶甲醇提取物对高血压 L-NAME 大鼠的降压作用。采用非侵入性间接尾套容积描记法测量收缩压(SBP)。使用了四组大鼠:对照组;用 L-NAME(32mg/kg/天)治疗的高血压组;用依那普利(15mg/kg/天)作为参考降压药治疗的阳性对照组;以及用 L-NAME 加甲醇提取物(40mg/kg/天)治疗的组。

方法

单独使用 L-NAME 会导致 SBP 逐渐升高。4 周后,SBP 值达到 160±2mmHg,表明高血压的发生。依那普利可预防 SBP 的升高,在治疗 4 周后,SBP 仍保持正常,为 123±1mmHg。用 L-NAME 加甲醇提取物治疗也可预防 SBP 的升高,在治疗 4 周后,SBP 仍保持在 115±1mmHg。在离体模型中,甲醇提取物对预收缩的主动脉环产生松弛作用(在 3g/L 时产生 54 ± 2%的松弛)。但是,当环被剥除时,甲醇提取物未能使预收缩的主动脉环松弛。旋覆花甲醇提取物的植物化学研究表明,存在酚类化合物,如紫菀酮和绿原酸。

结果

本研究结果表明,旋覆花甲醇提取物具有降压作用,主要通过内皮依赖性血管舒张作用介导。紫菀酮和绿原酸具有很强的血管舒张作用,可能参与了植物提取物的降压作用。生物信息学 POM 分析证实了紫菀酮和绿原酸作为多种生物靶标抑制剂的治疗潜力。基于这些结果,应研究这些植物化学物质与钙和过渡金属的配位,以更好地开发抗高血压药物。

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