de Carvalho Enaile Salviano, Tirloni Cleide Adriane Signor, Palozi Rhanany Alan Calloi, Schaedler Maysa Isernhagen, Guarnier Lucas Pires, Silva Aniely Oliveira, Mota Jonas da Silva, Cardoso Claudia Andréa Lima, de Barros Márcio Eduardo, Gasparotto Junior Arquimedes
Faculdade de Ciências da Saúde, Universidade Federal da Grande Dourados, Dourados, MS, Brazil.
Centro de Estudos em Recursos Naturais, Universidade Estadual de Mato Grosso do Sul, Dourados, MS, Brazil.
Evid Based Complement Alternat Med. 2019 Jan 2;2019:4109810. doi: 10.1155/2019/4109810. eCollection 2019.
This work provides the first demonstration that ethanolic extract (EEEG) obtained from leaves (EEEG) and its butanolic fraction (ButFr) has important vasodilatory effects on isolated mesenteric vascular beds (MVBs). First, the EEEG was obtained and a liquid-liquid fractionation was performed. EEEG and its resulting fractions were analyzed by high-performance liquid chromatography. Then, the vasodilatory effects of EEEG and their respective fractions were evaluated. Finally, the molecular mechanisms involved in the vasodilator responses of the EEEG and ButFr were also investigated. EEEG vasodilator response was estimated at ~11 and 18 mm Hg at doses of 0.1 and 0.3 mg, respectively. Moreover, it was found that ButFr was able to induce an expressive dose-dependent vasodilator response in MVBs. The PP reduction values for doses of 0.1 and 0.3 mg were ~10 and 28 mm Hg, respectively. Endothelium removal or inhibition of nitric oxide and prostaglandin synthase (by L-NAME plus indomethacin) inhibited the vasodilatory effects induced by ButFr or EEEG. The peak effect of ButFr and EEEG doses (0.1 and 0.3 mg) was decreased by ~100% (p < 0.001). The association of atropine plus HOE-140 fully inhibited EEEG and ButFr-induced vasodilation (p < 0.001). Moreover, perfusion with nutritive solution containing 40 mM KCl or previous treatment with tetraethylammonium completely blocked vasodilation induced by ButFr (p < 0.001). This study showed that EEEG and its ButFr have important vasodilatory effects by endothelial M3-muscarinic and B2-bradykininergic receptors inducing nitric oxide and prostacyclin release followed by K+ channels activation in the vascular smooth muscle.
这项研究首次证明，从树叶中提取的乙醇提取物（EEEG）及其丁醇馏分（ButFr）对离体肠系膜血管床（MVBs）具有重要的血管舒张作用。首先，获取EEEG并进行液-液分级分离。通过高效液相色谱法对EEEG及其所得馏分进行分析。然后，评估EEEG及其各个馏分的血管舒张作用。最后，还研究了EEEG和ButFr血管舒张反应所涉及的分子机制。EEEG在剂量分别为0.1和0.3 mg时，血管舒张反应估计分别为约11和18 mmHg。此外，发现ButFr能够在MVBs中诱导明显的剂量依赖性血管舒张反应。0.1和0.3 mg剂量下的血压降低值分别约为10和28 mmHg。去除内皮或抑制一氧化氮和前列腺素合酶（通过L-NAME加吲哚美辛）可抑制ButFr或EEEG诱导的血管舒张作用。ButFr和EEEG剂量（0.1和0.3 mg）的峰值效应降低了约100%（p < 0.001）。阿托品加HOE-140联合使用完全抑制了EEEG和ButFr诱导的血管舒张（p < 0.001）。此外，用含40 mM KCl的营养液灌注或先前用四乙铵处理可完全阻断ButFr诱导的血管舒张（p < 0.001）。这项研究表明，EEEG及其ButFr通过内皮M3-毒蕈碱和B2-缓激肽能受体诱导一氧化氮和前列环素释放，随后激活血管平滑肌中的钾通道，从而具有重要的血管舒张作用。
