Anti-atherogenic and anti-angiogenic activities of polyphenols from propolis
Julio Beltrame Dalepranea,b, Vanessa da Silva Freitasb, Alejandro Pachecoc, Martina Rudnickib, Luciane Aparecida Faineb, Felipe Augusto Dörrb, Masaharu Ikegakid, Luis Antonio Salazarc, Thomas Prates Onga, Dulcinéia Saes Parra Abdallab,⁎
aDepartment of Food and Experimental Nutrition, Faculty of Pharmaceutical Sciences, University of Sao Paulo, Sao Paulo, Brazil b Department of Clinical and Toxicology Analysis, Faculty of Pharmaceutical Sciences, University of Sao Paulo, Sao Paulo, Brazil c Department of Basic Science, Faculty of Medicine, Universidad de La Frontera, Temuco, Chile d Department of Pharmacy, Federal University of Alfenas, Alfenas, MG, Brazil
Propolis is a polyphenol-rich resinous substance extensively used to improve health and prevent diseases. The effects of polyphenols from different sources of propolis on atherosclerotic lesions and inflammatory and angiogenic factors were investigated in LDL receptor gene (LDLr−/−) knockout mice. The animals received a cholesterol-enriched diet to induce the initial atherosclerotic lesions (IALs) or advanced atherosclerotic lesions (AALs). The IAL or AAL animals were divided into three groups, each receiving polyphenols from either the green, red or brown propolis (250 mg/kg per day) by gavage. After 4 weeks of polyphenol treatment, the animals were sacrificed and their blood was collected for lipid profile analysis. The atheromatous lesions at the aortic root were also analyzed for gene expression of inflammatory and angiogenic factors by quantitative real-time polymerase chain reaction and immunohistochemistry. All three polyphenol extracts improved the lipid profile and decreased the atherosclerotic lesion area in IAL animals. However, only polyphenols from the red propolis induced favorable changes in the lipid profiles and reduced the lesion areas in AAL mice. In IAL groups, VCAM, MCP-1, FGF, PDGF, VEGF, PECAM and MMP-9 gene expression was down-regulated, while the metalloproteinase inhibitor TIMP-1 gene was up-regulated by all polyphenol extracts. In contrast, for advanced lesions, only the polyphenols from red propolis induced the down-regulation of CD36 and the up-regulation of HO-1 and TIMP-1 when compared to polyphenols from the other two types of propolis. In conclusion, polyphenols from propolis, particularly red propolis, are able to reduce atherosclerotic lesions through mechanisms including the modulation of inflammatory and angiogenic factors.
© 2011 Elsevier Inc. All rights reserved.
* THESE STATEMENTS HAVE NOT BEEN EVALUATED BY THE FOOD AND DRUG ADMINISTRATION. THIS IS NOT INTENDED TO DIAGNOSE, TREAT CURE OR PREVENT ANY DISEASE.