Aqueous fraction from Costus spiralis (Jacq.) Roscoe leaf reduces contractility by impairing the calcium inward current in the mammalian myocardium

作者：Britto Raquel Moreira; Santos Andre Luiz; Cruz Jader Santos; Santana Gondim Antonio Nei; Lauton Santos Sandra; Lara Aline; Guatimosim Silvia; Lins Vasconcelos Carla Maria; Estevame Charles dos Santos; Dias Antonio Santos; Oliveira Evaleide Diniz; Lima Adriana Karla; Souza Rejane Cardoso; Conde Garcia Eduardo Antonio^*

来源：Journal of Ethnopharmacology, 2011, 138(2): 382-389.

DOI：10.1016/j.jep.2011.09.013

• Costus spiralis
• Cardiac arrhythmias
• Contractility
• Myocardium
• Calcium

Ethnopharmacological relevance: Brazilian folk medicine uses infusion of Costus spiralis leaf to help people to treat arterial hypertension and syndromes of cardiac hyperexcitability.
Aim of the study: Evaluate the aqueous fraction (AqF) effect on atrial contractility and investigate its mechanism of action.
Materials and methods: 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 AgF. The role of calcium in this effect was ago 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.
Results: 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)= 8948 +/- 1346 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 AgF. However, this fraction decreased the force overshoot characteristic of the Bowditch's phenomenon, and shifted the concentration-response curve for CaCl2 (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 (1-1000 pM) and BAY K8644 (5-2000 nM) showed that AqF abolished the inotropic effect of these substances. On cardiomyocytes, 48 mg/l AqF reduced (similar to 23%) the L-type calcium current density from -6.3 +/- 03 to 4.9 +/- 0.2 A/F (n = 5 cells, p < 0.05) and reduced the intracellular calcium transient (similar to 20%, 4.7 +/- 1.2 au., n = 42 cells to 3.7 +/- 1.00 au., 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).
Conclusions: 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.

• 出版日期2011-11-18