Berberine ameliorates inflammation in patients with acute coronary syndrome following percutaneous coronary intervention.

1. Inflammation is central to the pathogenesis of acute coronary syndrome (ACS) and is associated with adverse clinical outcomes after percutaneous coronary intervention (PCI). Recent in vitro work has demonstrated the anti-inflammatory effect of berberine, a primary component of the traditional Chinese medicine 'umbellatine'. In the present study, we further tested whether berberine had any beneficial effects on ACS patients following PCI. 2.In all, 130 ACS patients undergoing PCI were recruited to the present study. Sixty-one patients were treated with berberine (300 mg, t.i.d., for 30 days) in addition to standard therapy, whereas the remaining patients received standard therapy alone. Circulating inflammatory markers were measured by ELISA, whereas serum lipid profiles were measured by routine chemical assays. 3.In the berberine-treated group, matrix metalloproteinase (MMP)-9, intercellular adhesion molecule (ICAM)-1, vascular cell adhesion molecule (VCAM)-1, C-reactive protein, interleukin-6 and monocyte chemoattractant protein-1 were significantly reduced relative to baseline values. Furthermore, the changes in MMP-9, ICAM-1 and VCAM-1 from baseline to after 1 month of treatment differed significantly between the two patient groups. There was a tendency for berberine to induce a slightly greater reduction in low-density lipoprotein cholesterol and triglycerides than standard therapy alone, without affecting high-density lipoprotein cholesterol, but the differences failed to reach statistical significance. No severe adverse effects of berberine were observed. 4.The results of the present study provide the first clinical evidence of the anti-inflammatory action of berberine in ACS patients following PCI. Berberine may become adjunct therapy to further improve clinical outcomes via its anti-inflammatory effect in ACS patients.

Artemisinin inhibits extracellular matrix metalloproteinase inducer (EMMPRIN) and matrix metalloproteinase-9 expression via a protein kinase Cδ/p38/extracellular signal-regulated kinase pathway in phorbol myristate acetate-induced THP-1 macrophages.

1. Overexpression of extracellular matrix metalloproteinase inducer (EMMPRIN) and matrix metalloproteinases (MMPs) by monocytes/macrophages has been proposed to play a significant role in atherosclerotic plaque progression and rupture. The aim of the present study was to explore whether artemisinin, a natural extract from Artemisia annua, could decrease EMMPRIN and MMP-9 expression in phorbol myristate acetate (PMA)-induced macrophages by regulating the protein kinase (PK) Cδ/c-Jun N-terminal kinase (JNK)/p38/extracellular signal-regulated kinase (ERK) pathway. 2. Human monocytic THP-1 cells were pretreated with 20-80 µg/mL artemisinin for 4 h or 1-10 µmol/L rottlerin for 1 h prior to stimulation with PMA (100 nmol/L) for another 48 h. Cells were collected to analyse the induction of EMMPRIN and MMP-9. Upstream pathway analysis using the PKCδ inhibitor rottlerin detected activation of the PKCδ/JNK/p38/ERK pathway. 3. Artemisinin (20-80 µg/mL) significantly inhibited the induction of EMMPRIN and MMP-9 at both the transcriptional and translational levels in a dose-dependent manner in PMA-induced macrophages. In addition, artemisinin (20-80 µg/mL) strongly blocked PKCδ/JNK/p38/ERK MAPK phosphorylation. The PKCδ inhibitor rottlerin (1-10 µmol/L) also significantly inhibited JNK/p38/ERK phosphorylation and decreased EMMPRIN and MMP-9 mRNA and protein expression. 4. The results of the present study suggest that artemisinin inhibits EMMPRIN and MMP-9 expression and activity by suppressing the PKCδ/ERK/p38 cascade in PMA-induced macrophages.