Abstract

Patagonian calafate (Berberis microphylla) is a native dark purple berry reported with the highest antioxidant profile from a collection of endemic southern chilean fruits; the pharmacology of this fruit has been scarcely investigated. Chemically, the berry has a high acorbic acid and polyphenolic content which includes anthocianins, flavonols and phenolic acid derivatives. Since red berries cultured in southern Chile have a beneficial effect in chronic vascular diseases, we proposed that extracts of calafate berries might have be vasoactive and present a favorable cellular antioxidant profile. To this aim, ethanol or acetone calafate extracts (1-300 µg/ml), were evaluated as mesenteric bed vasodilators previosly contracted with 50 µM noradrenaline and assessed whether the effect involves endotelial nitric oxide (NO) production and release. Cellular antioxidant activity was evaluated in isolated endothelial cells. Calafate extracts elicited a concentration-dependent antioxidante activity comparable to that of quercetin standards. Extracts elicited a concentration-dependent vasodilator response with an EC50 of 3.5 µg/ml; the maximal response was reached with 10-30 µg/mL (which caused a 75-80% vasodilatation in noradrenaline precontracted preparations). The vasodilatation was significantly reduced by either endothelium removal (after a 90 sec 0.1% saponin perfusion) or eNOS inhibition with 150 µM N-nitro-L-arginine. Moreover, relaxation significantly correlated with the concentration-dependent extract NO production (R2 =0.8, p<0.05). The chemical polyphenol extract profile (derived from HPLC-ESI-MS/MS analysis), identified delphindin, petunidin and malvidin as 3-glucosides as the main extract polyphenols. We are in the process of assessing whether these molecules could partially explain the extracts induced-vascular responses. In conclusion, the calafate berry extracts elicited a potent endothelium-dependent vascular relaxation coupled NO production, a vascular response likely linked to its cellular antioxidant properties.