Beneficial effects of hydroalcoholic extract and flavonoids from Zuccagnia punctata in a rabbit model of vascular dysfunction induced by high cholesterol diet

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.