Beneficial effects of hydroalcoholic extract and flavonoids from Zuccagnia punctata in a rabbit model of vascular dysfunction induced by high cholesterol diet
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.
KeywordsZuccagnia punctata Hypercholesterolemia Rabbit aorta Angiotensin II Vascular dysfunction Flavonoids
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.
Compliance with ethical standards
Conflict of interest
The authors declare that they have no competing interests.
- Agüero MB, González M, Lima B, Svetaz L, Sánchez M, Zacchino S, Egly Feresin G, Schmeda-Hirschmann G, Palermo J, Wunderlin D, Tapia A (2010) Argentinean propolis from Zuccagnia punctata Cav. (Caesalpinieae) exudates: phytochemical characterization and antifungal activity. J Agric Food Chem 58:194–201CrossRefPubMedGoogle Scholar
- Balasuriya NBW, Vasantha Rupasinghe HP (2011) Plant flavonoids as angiotensin converting enzyme inhibitors in regulation of hypertension. Funct Foods Health Dis 5:172–188Google Scholar
- Butassi E, Svetaz LA, Ivancovich JJ, Feresin GE, Tapia A, Zacchino SA (2015) Synergistic mutual potentiation of antifungal activity of Zuccagnia punctata Cav. and Larrea nitida Cav. extracts in clinical isolates of Candida albicans and Candida glabrata. Phytomedicine 22:666–678CrossRefPubMedGoogle Scholar
- Jespersen B., Tykocki NR, Watts SW, Cobbett PJ (2015). Measurement of smooth muscle function in the isolated tissue bath-applications to pharmacology research. J Vis Exp. (95), e52324, doi: 10.3791/52324
- Moreno A, Nuño G, Cuello S, Sayago JE, Alberto MR, Zampini C, Isla MI (2015a) Anti-inflammatory, antioxidant and antimicrobial activity characterization and toxicity studies of flowers of “jarilla”, a medicinal shrub from Argentina. Nat Prod Commun 6:991–994Google Scholar
- Ulibarri EA (2005) Zuccagnia punctata (Leguminosae) ¿Nuevo o viejo endemismo argentino? Darwiniana 43:212–215Google Scholar
- Vessal M, Hemmati M, Vasei M (2003) Antidiabetic effects of quercetin in streptozocin-induced diabetic rats. Comp Biochem Physiol C 135C:357–364Google Scholar
- Zampini IC, Villena J, Salva S, Herrera M, Isla MI, Alvarez S (2012) Potentiality of standardized extract and isolated flavonoids from Zuccagnia punctata for the treatment of respiratory infections by Streptococcus pneumoniae: in vitro and in vivo studies. J Ethnopharmacol 140:287–292CrossRefPubMedGoogle Scholar