Berberine reduces both MMP-9 and EMMPRIN expression through prevention of p38 pathway activation in PMA-induced macrophages

Background: Overproduction of MMPs (matrix metalloproteinases) and EMMPRIN (extracellular matrix metalloproteinase inducer) by monocytes/macrophages leads to atherosclerotic plaque rupture by degrading the extracellular matrix. Serum MMP-9 levels may therefore represent a novel marker of inflammation in patients with known coronary artery disease. The purpose of our study was to determine if berberine, a natural extract from Rhizoma coptidis, had any effect on the expression of MMP-9 and EMMPRIN in PMA-induced macrophages. Methods: Human monocytic THP-1 cells were pretreated with berberine for 1 h, and then induced by PMA for 48 h. Total RNA and protein were collected for Real-time PCR and Western blot analysis, respectively. Culture supernatants were collected to determine MMP-9 activity. Results: In the present study, we demonstrated that berberine inhibited the expression of MMP-9 and EMMPRIN at both the mRNA and protein levels in a dose-dependent manner in PMA-induced macrophages, and that it also reduced MMP-9 activity. Furthermore, berberine also suppressed p38 signaling pathway activation in PMA-induced macrophages. Conclusions: The data indicate that berberine reduces MMP-9 and EMMPRIN expression by suppressing the activation of p38 pathway in PMA-induced macrophages. This suggests a potential role for berberine as a therapeutic aid for stabilizing atherosclerotic plaque. (C) 2009 Elsevier Ireland Ltd. All rights reserved.