Abstract 19976: A New Combination of Nutraceutics Activates eNOS Through Plc/pkc-alpha/akt Signalling

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Introduction: Nutraceutics are medicinal foods that in certain components may exert a beneficial effect on cardiovascular system and represent a new opportunity for the maintenance of cardiovascular homeostasis. To date, despite its beneficial effects, the mechanisms involved are not completely clarified.

Hypothesis: Here, we aimed to characterize the vascular action of AkP05 (IzzeK®, Akademy Pharma), a new nutraceutic that combines Bacopa monniera, Ginkgo biloba, phosphatidylserine and extract of Green tea leaves in a certain concentration and purification, patent based.

Methods: We performed vascular reactivity studies on mice resistance vessels placed on pressure myograph evaluating the effects of increasing doses of AkP05 on phenylephrine-preconstricted vessels. In addition, to characterize the molecular mechanism we performed immunohistochemistry and Western Blot analyses.

Results: We demonstrate that AkP05 was able to induce dose-dependent vasodilatation of the mice mesenteric arteries, which was significantly reduced by pretreatment with L-NAME, an inhibitor of Nitric oxide synthase. This effect was associated with the phosphorylation on serine 1177 of eNOS. The use of wormannin, a PI3K inhibitor, did not modify the vasodilating action of Akp05, thus excluding its involvement in AkP05 signaling. The inhibition of phospholipase C (PLC), PKCα, or Akt significantly reduced the vasorelaxation evoked by Akp05, indicating that its effect was mediated by the PLC/PKCα /Akt/eNOS. In agreement, western blot analysis revealed that vascular treatment with AkP05 evoked phosphorylations of PKCα, Akt and eNOS. These phosphorylations were inhibited by PLC-inhibitor, thus demonstrating that PLC is the first signal activated by AkP05 converging on PKCα, AKT and eNOS. Over the direct action on NO production, AkP05 exerted an antioxidant effect modulating the activity of NADPH oxidase through the inhibition of Rac-1. Finally, the in vivo administration of AkP05 was able to evoke a reduction in blood pressure levels and this effect was absent in eNOS-deficient mice.

Conclusions: These data suggest that AkP05 could be used as a new dietary supplement to combat vascular disease related to eNOS dysfunction.

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