SEOUL, Korea—Korean researchers found cocoa polyphenol extract (CPE) reduced TNF-alpha-induced up-regulation of vascular endothelial growth factor—which is associated with tumorigenesis, cardiovascular disease (CVD), rheumatoid arthritis and psoriasis—by directly inhibiting PI3K and MEK1 activities, which may contribute to its chemopreventive potential (Br J Nutr. 2010 Oct;104(7):957-64)
Researchers tested whether cocoa polyphenol extract (CPE), known for its antioxidant and anti-inflammatory effects, inhibited TNF-alpha, a pro-inflammatory cytokine that has a vital role in the pathogenesis of inflammatory diseases such as cancer and psoriasis, -induced VEGF expression in promotion-sensitive JB6 mouse epidermal cells. CPE significantly inhibited TNF-alpha-induced up-regulation of VEGF via reducing TNF-alpha-induced activation of the nuclear trangascription factors activator protein-1 (AP-1) and NF-κB, which are key regulators of VEGF expression. CPE also inhibited TNF-alpha-induced phosphorylation of protein kinase B (Akt) and extracellular signal-regulated kinase. CPE blocked activation of their downstream kinases, p70 kDa ribosomal protein S6 kinase and p90 kDa ribosomal protein S6 kinase. CPE suppressed phosphoinositide 3-kinase (PI3K) activity via binding PI3K directly. CPE did not affect TNF-alpha-induced phosphorylation of mitogen-activated protein kinase kinase-1 (MEK1) but suppressed TNF-alpha-induced MEK1 activity.