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Polyphenol‐rich fruit modulate endothelial cell function via PI3 Kinase/Akt Pathway in Vitro in Human Umbilical Vein Endothelial Cell (HUVEC)

Polyphenolic antioxidants modulate endothelial function via a redox‐sensitive mechanism. However, the exact mechanism is not known. We hypothesize that polyphenols in extracts of grape seed (GS), strawberry (SB) and blueberry (BB), induce the redox‐sensitive phosphoinositide 3‐kinase (PI3K)/protein kinase B (Akt) pathway and activate downstream signals resulting in optimal endothelial cell function. HUVEC were treated with different concentrations (0.02–2 mg/mL) of GS, SB or BB extracts. Culture containing 0.2 mg/mL extracts increased p‐Akt levels significantly (p<0.05, n=6); GS by 2.3 ± 0.2‐fold, BB by 1.3 ± 0.1‐fold, and SB by 1.2 ± 0.1‐fold compared to PBS control. However, solutions containing >1 mg/mL GS and BB extracts caused cell death after 6 h exposure. Cell migration studies showed significantly (p<0.05, n=6) enhanced migration when cells were treated with solutions containing 0.2 mg/mL extracts. Tube formation increased when cells were treated with 0.02 mg/mL GS extract and 0.2 mg/mL BB or SB extracts. Both tube formation and cell migration significantly decreased in the presence of wortmannin (PI3K inhibitor). These data suggest a PI3/Akt‐dependent mechanism for endothelial function induced by fruit extracts rich in phenolic antioxidants. This study also provides evidence for phenolic‐/redox mediated contributions to wound healing, angiogenesis, and cell death.