Polyphenols from Chilean Propolis and Pinocembrin Reduce MMP-9 Gene Expression and Activity in Activated Macrophages.
Polyphenols from diverse sources have shown anti-inflammatory activity. In the context of atherosclerosis, macrophages play important roles including matrix metalloproteinases synthesis involved in degradation of matrix extracellular components affecting the atherosclerotic plaque stability. We prepared a propolis extract and pinocembrin in ethanol solution. Propolis extract was chemically characterized using LC-MS. The effect of treatments on gene expression and proteolytic activity was measured in vitro using murine macrophages activated with LPS. Cellular toxicity associated with both treatments and the vehicle was determined using MTT and apoptosis/necrosis detection assays. MMP-9 gene expression and proteolytic activity were measured using qPCR and zymography, respectively. Thirty-two compounds were identified in the propolis extract, including pinocembrin among its major components. Treatment with either ethanolic extract of propolis or pinocembrin inhibits MMP-9 gene expression in a dose-dependent manner. Similarly, an inhibitory effect was observed in proteolytic activity. However, the effect showed by ethanolic extract of propolis was higher than the effect of pinocembrin, suggesting that MMP-9 inhibition results from a joint contribution between the components of the extract. These data suggest a potential role of polyphenols from Chilean propolis in the control of extracellular matrix degradation in atherosclerotic plaques.
Center of Molecular Biology and Pharmacogenetics, Department of Basic Sciences, Scientific and Technological Bioresource Nucleus, Universidad de La Frontera, Avenida Francisco Salazar 01145, 4811230 Temuco, Chile.
Nicolás
N
Saavedra
Center of Molecular Biology and Pharmacogenetics, Department of Basic Sciences, Scientific and Technological Bioresource Nucleus, Universidad de La Frontera, Avenida Francisco Salazar 01145, 4811230 Temuco, Chile.
Alejandro
A
Cuevas
Department of Clinical and Toxicological Analyses, Faculty of Pharmaceutical Sciences, Universidade de São Paulo, Avenida Professor Lineu Prestes 580, 05508-000 São Paulo, SP, Brazil.
Marcela F
MF
Cavalcante
Department of Clinical and Toxicological Analyses, Faculty of Pharmaceutical Sciences, Universidade de São Paulo, Avenida Professor Lineu Prestes 580, 05508-000 São Paulo, SP, Brazil.
Felipe A
FA
Dörr
Center of Molecular Biology and Pharmacogenetics, Department of Basic Sciences, Scientific and Technological Bioresource Nucleus, Universidad de La Frontera, Avenida Francisco Salazar 01145, 4811230 Temuco, Chile.
Kathleen
K
Saavedra
Center of Molecular Biology and Pharmacogenetics, Department of Basic Sciences, Scientific and Technological Bioresource Nucleus, Universidad de La Frontera, Avenida Francisco Salazar 01145, 4811230 Temuco, Chile.
Tomás
T
Zambrano
Department of Clinical and Toxicological Analyses, Faculty of Pharmaceutical Sciences, Universidade de São Paulo, Avenida Professor Lineu Prestes 580, 05508-000 São Paulo, SP, Brazil.
Dulcineia S P
DS
Abdalla
Center of Molecular Biology and Pharmacogenetics, Department of Basic Sciences, Scientific and Technological Bioresource Nucleus, Universidad de La Frontera, Avenida Francisco Salazar 01145, 4811230 Temuco, Chile.
Luis A
LA
Salazar
D000818:Animals; D017209:Apoptosis; D050197:Atherosclerosis / Q000378:metabolism; D002470:Cell Survival; D002853:Chromatography, Liquid; D044950:Flavanones / Q000737:chemistry*; D020869:Gene Expression Profiling; D008070:Lipopolysaccharides; D008262:Macrophage Activation; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism*; D013058:Mass Spectrometry; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D051379:Mice; D009336:Necrosis; D058226:Plaque, Atherosclerotic / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D059808:Polyphenols / Q000737:chemistry*; D011429:Propolis / Q000737:chemistry; D000067996:RAW 264.7 Cells
D044950:Flavanones; D008070:Lipopolysaccharides; D059808:Polyphenols; C016063:pinocembrin; D011429:Propolis; D020780:Matrix Metalloproteinase 9; C501830:Mmp9 protein, mouse