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Berberine reduces both MMP-9 and EMMPRIN expression through prevention of p38 pathway activation in PMA-induced
Zhouqing Huang1, Liansheng Wang, Shu Meng
1Department of Cardiology, XinHua Hospital, Shanghai Jiaotong University Medical School, 1665 Kongjiang Road, Shanghai, 200092, PR China. susiehzq@yahoo.cn
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.
Insights
Berberine, a natural compound, effectively reduces matrix metalloproteinase-9 (MMP-9) and EMMPRIN expression in macrophages. This finding suggests berberine
Area of Science:
- Biochemistry
- Cell Biology
- Pharmacology
Background:
- Monocyte/macrophage overproduction of MMPs and EMMPRIN degrades extracellular matrix, contributing to atherosclerotic plaque rupture.
- Elevated serum MMP-9 levels may indicate inflammation in coronary artery disease patients.
Purpose of the Study:
- To investigate the effect of berberine, a natural extract, on MMP-9 and EMMPRIN expression in PMA-induced macrophages.
Main Methods:
- Human monocytic THP-1 cells were pretreated with berberine and induced with PMA.
- Real-time PCR, Western blot, and activity assays were used to analyze MMP-9 and EMMPRIN expression and activity.
- p38 signaling pathway activation was assessed.
Main Results:
- Berberine dose-dependently inhibited MMP-9 and EMMPRIN expression at mRNA and protein levels.
- Berberine reduced MMP-9 activity in PMA-induced macrophages.
- Berberine suppressed p38 signaling pathway activation.
Conclusions:
- Berberine reduces MMP-9 and EMMPRIN expression by inhibiting p38 pathway activation in macrophages.
- Berberine shows potential as a therapeutic agent for stabilizing atherosclerotic plaque.