Inotropic effect of Citrus sinensis (L.) Osbeck leaf extracts on the guinea pig atrium

Abstract

The objective of the present investigation was to determine the contractile effect of crude and acetone leaf extracts of Citrus sinensis (L.) Osb. on mammalian myocardium. Crude leaf extracts have been used in folk medicine to treat neurological disorders. Some flavonoids isolated from this plant presented a positive inotropic effect on myocardium. This motivated us to test the extracts on the atria of guinea pigs of both sexes (300-500 g) and surprisingly we observed inotropic depression instead of an increase in force. The maximum effect of the crude extract was 79.4 ± 8.1% of the control force amplitude (N = 5 hearts, 10 trials, 27 ± 0.1ºC, stimulus: 2 Hz, 400 V, 0.5 ms). The EC 50 for crude, ethanol, acetic, aqueous, and acetone extracts was 300, 300, 600, 1000, and 140 µg/ml, respectively, with a Hill constant of 1.8, 2.0, 2.5, 2.0, and 1.4, respectively. Blockade of cholinergic, beta-adrenergic, or opioid membrane receptors with 1.5 µM atropine sulfate, 1 µM propranolol, and 10 µM naloxone, respectively, did not change the effect of the crude extract. The acetone extract abolished the Bowditch positive staircase phenomenon (N = 5 hearts, 10 trials, 27 ± 0.1ºC), suggesting a possible reduction of the calcium inward current, and also promoted the so-called Woodworth phenomenon. The effect was concentration-dependent and indicated the existence of another inhibitory contractile mechanism such as the simultaneous activation of some of the membrane potassium channels reducing the myocardial action potential duration and further decreasing the cellular calcium entry.

Chemistry and Pharmacology of Citrus sinensis

“…The water-ethanol and acetone leaf extracts of C. sinensis showed inotropic depression on the atria of guinea pigs of both sexes (300–500 g) having values of EC 50 of 300 µg/mL and 140 µg/mL, respectively. Drugs control naloxone (10 μM), propranolol (1.5 μM atropine sulfate), atropine sulfate (1 μM propranolol), did not change the effect of the crude extract [92]. In fact, cardiovascular medications are indicated for and/or used to treat many different disorders, conditions and diseases affecting the cardiovascular system, but in some cases could produce intensified effects, toxic levels, side effects and/or adverse effects.…”

Comparative Pharmacognostic Evaluation of Leaves of Citrus sinensis Var. Jaffa and Citrus paradisi var. Redblush

“…7,8,9,10 Leaf extracts have shown antioxidant, antifungal, anti-Helicobacter pylori and larvicidal activity against the dengue vector and negative ionotropic activities in experimental studies. 11,12,13,14,15 The leaf oil has insecticidal activity against larvae of Culex pipiens molestus mosquito. 16 Citrus paradisi (Macf.)…”