Abstract
This study evaluated the effects of a Zuccagnia punctata standardized hydroalcoholic extract (ZpE) and three of its major flavonoids [2′,4′-dihydroxychalcone (DHC), 7-hydroxyflavanone (HF) and 3,7-dihydroxyflavone (DHF)] on the vascular reactivity of aortic rings with endothelial dysfunction induced by feeding rabbits on a high cholesterol diet. Rabbits were fed with either normal chow or a diet containing 1% cholesterol for 5–6 weeks. Isometric contractions were measured. Concentration response curves to ZpE (range from 4 × 10−2 to 4 × 10 µg gallic acid equivalent/ml), DHC, DHF or HF (range from 10−9 to 10−4 M) showed concentration-dependent relaxation of arteries pre-contracted with phenylephrine. ZpE (4 × 10−2, 4 × 10−1 and 4 µg gallic acid equivalent/ml), HF (10−9, 10−7, 10−5 M), DHC (10−9 M) and DHF (10−9 M) added to the bath improved acetylcholine affinity. Pre-treatment of arteries with ZpE (4 × 10−2 µg gallic acid equivalent/ml) and DHC (10−9 M) reduced phenylephrine-induced contraction. Incubation with the higher dose of ZpE (4 µg gallic acid equivalent/ml) reduced the angiotensin II-maximal contraction (C max) acting as a non-competitive antagonist, while DHC and DHF (10−5 M) caused a non-parallel rightward of the angiotensin II-concentration response curves and reduced the C max acting as mixed antagonists. ZpE (4 × 10−2 µg gallic acid equivalent/ml), DHC and DHF (10−9 M) caused a rightward displacement of angiotensin II-concentration response curves acting as competitive antagonists. In conclusion, the present study demonstrated that a ZpE and its major flavonoids had beneficial effects in arteries with vascular dysfunction induced by hypercholesterolemia. Therefore its use as herbal medicine to prevent cardiovascular risks factors may be promising.
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Acknowledgements
This work was supported by grants from the Consejo de Investigaciones de la Universidad Nacional de Tucumán (PIUNT I521/1), Consejo de Investigaciones Científicas y Técnicas de la República Argentina (CONICET PIP 11-232), and Institutional funds from INSIBIO (Instituto Superior de Investigaciones Biológicas). We thank veterinary Rosa Alejandra Molina for bioterio management and Ms Erika Georgieff for her help in data collection.
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Roco, J., Alarcón, G., Sierra, L. et al. Beneficial effects of hydroalcoholic extract and flavonoids from Zuccagnia punctata in a rabbit model of vascular dysfunction induced by high cholesterol diet. Med Chem Res 26, 2336–2344 (2017). https://doi.org/10.1007/s00044-017-1934-6
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DOI: https://doi.org/10.1007/s00044-017-1934-6