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.
Huang
Zhouqing
Z
Department of Cardiology, XinHua Hospital, Shanghai Jiaotong University Medical School, 1665 Kongjiang Road, Shanghai, 200092, PR China. susiehzq@yahoo.cn
Wang
Liansheng
L
Meng
Shu
S
Wang
Yue
Y
Chen
Ting
T
Wang
Changqian
C
D050197:Atherosclerosis / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D051926:Basigin / Q000235:genetics / Q000378:metabolism*; D001599:Berberine / Q000737:chemistry / Q000494:pharmacology*; D002273:Carcinogens / Q000494:pharmacology; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008264:Macrophages / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism*; D061965:Matrix Metalloproteinase Inhibitors; D009000:Monocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
C497886:BSG protein, human; D002273:Carcinogens; D061965:Matrix Metalloproteinase Inhibitors; D012333:RNA, Messenger; D001599:Berberine; D051926:Basigin; D048051:p38 Mitogen-Activated Protein Kinases; D020780:Matrix Metalloproteinase 9; D013755:Tetradecanoylphorbol Acetate