Laboratório de Biofísica do Coração, Departamento de Fisiologia, Universidade Federal de Sergipe, Aracaju, SE, Brazil.
J Ethnopharmacol. 2011 Nov 18;138(2):382-9. doi: 10.1016/j.jep.2011.09.013. Epub 2011 Sep 22.
Brazilian folk medicine uses infusion of Costus spiralis leaf to help people to treat arterial hypertension and syndromes of cardiac hyperexcitability.
Evaluate the aqueous fraction (AqF) effect on atrial contractility and investigate its mechanism of action.
The AqF effect on the cardiac contractility was studied on isolated electrically driven guinea pig left atria. Atropine and tetraethylammonium (TEA) were employed to investigate whether potassium contributes for the inotropic mechanism of the AqF. The role of calcium in this effect was also studied. This was done by analysing the AqF effect on the Bowditch's phenomenon, as well as by studying whether it could interfere with the concentration-effect curve for CaCl(2), isoproterenol, and BAY K8644. Mice isolated cardiomyocytes were submitted to a whole-cell patch-clamp technique in order to evaluate whether the L-type calcium current participates on the AqF effect. Furthermore, the intracellular calcium transient was studied by confocal fluorescence microscopy.
AqF depressed the atrial contractile force. It was the most potent fraction from C. spiralis leaf (EC(50)=305 ± 41 mg/l) (crude extract: EC(50)=712 ± 41; ethyl acetate: EC(50)=788 ± 121; chloroform: EC(50)=8,948 ± 1,346 mg/l). Sodium and potassium content in the AqF was 0.15 mM and 1.91 mM, respectively. Phytochemical analysis revealed phenols, tannins, flavones, xanthones, flavonoids, flavonols, flavononols, flavonones, and saponins. Experiments with atropine and TEA showed that potassium does not participate of the inotropic mechanism of AqF. However, this fraction decreased the force overshoot characteristic of the Bowditch's phenomenon, and shifted the concentration-response curve for CaCl(2) (EC(50) from 1.12 ± 0.07 to 7.23 ± 0.47 mM) indicating that calcium currents participate on its mechanism of action. Results obtained with isoproterenol (1-1,000 pM) and BAY K8644 (5-2000nM) showed that AqF abolished the inotropic effect of these substances. On cardiomyocytes, 48mg/l AqF reduced (∼23%) the L-type calcium current density from -6.3 ± 0.3 to -4.9 ± 0.2 A/F (n=5 cells, p<0.05) and reduced the intracellular calcium transient (∼20%, 4.7 ± 1.2 a.u., n=42 cells to 3.7 ± 1.00 a.u., n=35 cells, p<0.05). However, the decay time of the fluorescence was not changed (control: 860 ± 32 ms, n=42 cells; AqF: 876 ± 26 ms, n=35 cells, p>0.05).
The AqF of C. spiralis leaf depresses myocardial contractility by reducing the L-type calcium current and by decreasing the intracellular calcium transient. Despite the lack of data on the therapeutic dose of AqF used in folk medicine, our results support, at least in part, the traditional use of this plant to treat cardiac disorders.
巴西民间医学使用螺旋角豆叶的浸剂来帮助人们治疗动脉高血压和心脏兴奋过度综合征。
评估水提物（AqF）对心房收缩力的影响，并研究其作用机制。
在离体电驱动的豚鼠左心房上研究 AqF 对心脏收缩力的影响。采用阿托品和四乙铵（TEA）来研究钾是否为 AqF 变力机制的贡献者。还研究了钙在这种作用中的作用。通过分析 Bowditch 现象的 AqF 效应，以及研究它是否可以干扰 CaCl(2)、异丙肾上腺素和 BAY K8644 的浓度-效应曲线来实现这一点。用全细胞膜片钳技术对分离的心肌细胞进行研究，以评估 L 型钙电流是否参与 AqF 效应。此外，通过共聚焦荧光显微镜研究细胞内钙瞬变。
AqF 抑制了心房收缩力。它是螺旋角豆叶中最有效的部分（EC(50)=305 ± 41 mg/l）（粗提物：EC(50)=712 ± 41；乙酸乙酯：EC(50)=788 ± 121；氯仿：EC(50)=8948 ± 1346 mg/l）。AqF 中的钠和钾含量分别为 0.15 mM 和 1.91 mM。植物化学分析显示出酚类、单宁、类黄酮、蒽酮、类黄酮、黄酮醇、黄酮醇、黄酮、和皂苷。阿托品和 TEA 的实验表明，钾不参与 AqF 的变力机制。然而，该部分降低了 Bowditch 现象特征性的力过冲，并改变了 CaCl(2)的浓度-反应曲线（EC(50)从 1.12 ± 0.07 变为 7.23 ± 0.47 mM），表明钙电流参与其作用机制。用异丙肾上腺素（1-1000 pM）和 BAY K8644（5-2000nM）进行的实验表明，AqF 消除了这些物质的变力作用。在心肌细胞上，48mg/l AqF 降低了（约 23%）从 -6.3 ± 0.3 到 -4.9 ± 0.2 A/F 的 L 型钙电流密度（n=5 个细胞，p<0.05）并降低了细胞内钙瞬变（约 20%，4.7 ± 1.2 a.u.，n=42 个细胞到 3.7 ± 1.00 a.u.，n=35 个细胞，p<0.05）。然而，荧光的衰减时间没有改变（对照：860 ± 32 ms，n=42 个细胞；AqF：876 ± 26 ms，n=35 个细胞，p>0.05）。
螺旋角豆叶的 AqF 通过降低 L 型钙电流和减少细胞内钙瞬变来抑制心肌收缩力。尽管民间医学中使用的 AqF 的治疗剂量缺乏数据，但我们的结果至少部分支持了该植物用于治疗心脏疾病的传统用途。
