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

详细信息    查看全文

• 作者：Raquel Moreira  ; Britto^a ; André ; Luiz  ; Santos^a ; Jader Santos  ; Cruz^b ; Antonio Nei Santana  ; Gondim^b ;   ; ^c ; Sandra  ; Lauton-Santos^a ; Aline  ; Lara^d ; Silvia  ; Guatimosim^d ; Carla Maria Lins  ; Vasconcelos^a ; Charles dos Santos  ; Estevam^e ; Antonio Santos  ; Dias^e ; Evaleide Diniz  ; Oliveira^a ; Adriana Karla  ; Lima^a ; Rejane Cardoso  ; Souza^a ; Eduardo Antonio  ; Conde-Garcia^a ;   ; ^{egarcia@ufs.br}
• 关键词：Costus spiralis ; Cardiac arrhythmias ; Contractility ; Myocardium ; Calcium
• 刊名：Journal of Ethnopharmacology
• 出版年：2011
• 出版时间：18 November 2011
• 年：2011
• 卷：138
• 期：2
• 页码：382-389
• 全文大小：851 K

文摘

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 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¨Ceffect curve for CaCl₂, 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 (EC₅₀ = 305 ¡À 41 mg/l) (crude extract: EC₅₀ = 712 ¡À 41; ethyl acetate: EC₅₀ = 788 ¡À 121; chloroform: EC₅₀ = 8948 ¡À 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 AqF. However, this fraction decreased the force overshoot characteristic of the Bowditch's phenomenon, and shifted the concentration¨Cresponse curve for CaCl₂ (EC₅₀ from 1.12 ¡À 0.07 to 7.23 ¡À 0.47 mM) indicating that calcium currents participate on its mechanism of action. Results obtained with isoproterenol (1?000 pM) and BAY K8644 (5?000 nM) showed that AqF abolished the inotropic effect of these substances. On cardiomyocytes, 48 mg/l AqF reduced (?3 % ) the L-type calcium current density from ?.3 ¡À 0.3 to ?.9 ¡À 0.2 A/F (n = 5 cells, p < 0.05) and reduced the intracellular calcium transient (?0 % , 4.7 ¡À 1.2 a.u., n = 42 cells to 3.7 ¡À 1.00 a.u., n = 35 cells, p < 0.05). However, the decay time of the fluorescence was not changed (control: 860 ¡À 32 ms, n = 42 cells; AqF: 876 ¡À 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.