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燕尾苏铁(Dicksonia sellowiana Presl. HooK,苏铁科)水醇提取物对毒蕈碱受体的激活可诱导大鼠血管舒张和低血压。

Activation of muscarinic receptors by a hydroalcoholic extract of Dicksonia sellowiana Presl. HooK (Dicksoniaceae) induces vascular relaxation and hypotension in rats.

作者信息

Rattmann Yanna D, Crestani Sandra, Lapa Fernanda R, Miguel Obdúlio G, Marques Maria C A, da Silva-Santos J Eduardo, Santos Adair R S

机构信息

Department of Pharmacology, Centro Politécnico, Universidade Federal do Paraná, Curitiba, PR, Brazil.

出版信息

Vascul Pharmacol. 2009 Jan-Feb;50(1-2):27-33. doi: 10.1016/j.vph.2008.08.005. Epub 2008 Sep 6.

Abstract

Dicksonia sellowiana (Presl.) Hook is a native plant from the Central and South Americas that contain high levels of polyphenols, antioxidant compounds involved in protection against inflammation, cancer and cardiovascular risk. A phytomedicinal preparation obtained from aerial parts of D. sellowiana is currently under clinical evaluation in Brazil against asthma, and has been associated with several other beneficial effects. This study demonstrates that a hydroalcoholic extract obtained from D. sellowiana leaves (HEDS) fully relax, in a concentration-dependent manner, rat aortic rings precontracted with phenylephrine. Moreover, administration of HEDS (10, 20 and 40 mg/kg, i.v.) in anaesthetized rats resulted in a strong but reversible hypotension. Aortic relaxation induced by HEDS was abolished by endothelium removal, by incubation of the nitric oxide synthase inhibitor L-NAME, or the soluble guanylate cyclase inhibitor ODQ. In addition, this effect was partially inhibited by indomethacin (a cyclooxygenase inhibitor) and KT 5730 (a PKA inhibitor). The potassium channels blockade by either tetraethylammonium or charybdotoxin also resulted in a potent inhibition of HEDS-induced aortic relaxation, whereas apamine only slightly reduced it. In addition HEDS-induced relaxation was unchanged by 4-amynopiridine and glibenclamide. The selective muscarinic receptor antagonist atropine counteracted both aortic relaxation and blood pressure reduction generated by HEDS. Experiments using HPLC revealed the presence of high amounts of phenolic compounds in this extract. Taken together, our results reveal that the D. sellowiana possess substances with both in vivo and in vitro activities and that the vascular effect of HEDS involves activation of muscarinic receptors, stimulation of the nitric oxide pathway and opening of calcium-activated potassium channels.

摘要

南美苏铁(Dicksonia sellowiana (Presl.) Hook)是一种原产于中南美洲的植物,含有高水平的多酚,这些抗氧化化合物有助于预防炎症、癌症和心血管疾病风险。一种从南美苏铁地上部分获得的植物药制剂目前正在巴西进行抗哮喘的临床评估,并且已显示出其他一些有益效果。本研究表明,从南美苏铁叶中获得的水醇提取物(HEDS)能以浓度依赖的方式使预先用去氧肾上腺素收缩的大鼠主动脉环完全舒张。此外,在麻醉大鼠中静脉注射HEDS(10、20和40mg/kg)会导致强烈但可逆的低血压。去除内皮、用一氧化氮合酶抑制剂L-NAME或可溶性鸟苷酸环化酶抑制剂ODQ孵育后,HEDS诱导的主动脉舒张被消除。此外,这种作用被吲哚美辛(一种环氧化酶抑制剂)和KT 5730(一种蛋白激酶A抑制剂)部分抑制。用四乙铵或蝎毒素阻断钾通道也会有效抑制HEDS诱导的主动脉舒张,而阿帕明只会轻微降低这种舒张作用。此外,4-氨基吡啶和格列本脲对HEDS诱导的舒张作用没有影响。选择性毒蕈碱受体拮抗剂阿托品可抵消HEDS引起的主动脉舒张和血压降低。使用高效液相色谱法的实验表明该提取物中存在大量酚类化合物。综上所述,我们的结果表明南美苏铁含有具有体内和体外活性的物质,并且HEDS的血管效应涉及毒蕈碱受体的激活、一氧化氮途径的刺激以及钙激活钾通道的开放。

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