TNFα-induced endothelial activation is counteracted by polyphenol extract from UV-stressed cyanobacterium Arthrospira platensis

The cyanobacterium Arthrospira platensis has been considered as a potential source of several therapeutic compounds including antioxidant molecules such as phenolics. Several studies have demonstrated that the exposure to a particular stress factor, such as UV-light, is able to modify the quality and the quantity of polyphenols produced by A. platensis. In this study, we compare the effects of polyphenol extracts from A. platensis (PEAP) and from UV-stressed A. platensis (PEAP(UV)) on endothelial cells exposed to TNF alpha by evaluating the expression of endothelial Nitric Oxide Synthase (eNOS), of inducible Nitric Oxide Synthase (iNOS), of Vascular Cell Adhesion Molecule 1 (VCAM-1) and of Matrix Metalloproteinase-9 (MMP-9), and key markers of endothelial dysfunction. MMP-9 activity was measured by gel zymography. Western Blot analysis was performed to analyze eNOS, iNOS and VCAM-1 expression and signal transduction. The major evidence of this study is that PEAP(UV) is more efficient than PEAP in counteracting the TNF alpha-induced endothelial activation. Treatment with PEAP(UV) (0.10 mg(GAE)/ml) restored to basal levels the TNF alpha-induced expression of eNOS, iNOS, VCAM-1 and MMP-9 and the TNF alpha- triggered activation of Akt. The use of an Akt inhibitor mimicked the inhibitory effects of PEAP(UV) on eNOS and MMP-9 expression, suggesting that eNOS and MMP-9 induction by TNF alpha depends on Akt activation and that PEAP(UV) exerts its vaso-protective effect through Akt signalling inhibition. HPLC analysis confirmed a different composition both in polyphenols' quality and in quantity of the two extracts. In conclusion, this study shows that a stress factor such as UV-light exposure leads to the production by A. platensis of molecules to potentially be used against the onset and progression of vascular diseases associated with endothelial dysfunction.