title: Anti-atherogenic and anti-angiogenic activities of polyphenols from propolis.
abstract: 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.
authors.affiliation: Department of Food and Experimental Nutrition, Faculty of Pharmaceutical Sciences, University of Sao Paulo, Sao Paulo, Brazil.
authors.forename: Julio Beltrame
authors.initials: JB
authors.lastname: Daleprane
authors.forename: Vanessa da Silva
authors.initials: Vda S
authors.lastname: Freitas
authors.forename: Alejandro
authors.initials: A
authors.lastname: Pacheco
authors.forename: Martina
authors.initials: M
authors.lastname: Rudnicki
authors.forename: Luciane Aparecida
authors.initials: LA
authors.lastname: Faine
authors.forename: Felipe Augusto
authors.initials: FA
authors.lastname: Dörr
authors.forename: Masaharu
authors.initials: M
authors.lastname: Ikegaki
authors.forename: Luis Antonio
authors.initials: LA
authors.lastname: Salazar
authors.forename: Thomas Prates
authors.initials: TP
authors.lastname: Ong
authors.forename: Dulcinéia Saes Parra
authors.initials: DS
authors.lastname: Abdalla
mesh_terms: D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000378:metabolism; D050197:Atherosclerosis / Q000188:drug therapy* / Q000473:pathology / Q000517:prevention & control; D018932:Chemokine CCL2 / Q000235:genetics / Q000378:metabolism; D002784:Cholesterol / Q000097:blood; D015536:Down-Regulation; D005346:Fibroblast Growth Factors / Q000235:genetics / Q000378:metabolism; D007249:Inflammation / Q000188:drug therapy / Q000473:pathology / Q000517:prevention & control; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010936:Plant Extracts / Q000494:pharmacology*; D010982:Platelet-Derived Growth Factor / Q000235:genetics / Q000378:metabolism; D059808:Polyphenols / Q000494:pharmacology*; D011429:Propolis / Q000737:chemistry*; D060888:Real-Time Polymerase Chain Reaction; D011973:Receptors, LDL / Q000235:genetics / Q000378:metabolism; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation; D019010:Vascular Cell Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism; D042442:Vascular Endothelial Growth Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D020533:Angiogenesis Inhibitors; C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D010936:Plant Extracts; D010982:Platelet-Derived Growth Factor; D059808:Polyphenols; D011973:Receptors, LDL; C560825:Timp1 protein, mouse; D019715:Tissue Inhibitor of Metalloproteinase-1; D019010:Vascular Cell Adhesion Molecule-1; D042442:Vascular Endothelial Growth Factors; D005346:Fibroblast Growth Factors; D011429:Propolis; D002784:Cholesterol; D020780:Matrix Metalloproteinase 9; C501830:Mmp9 protein, mouse