Aqueous Fraction from Cucumis sativus Aerial Parts Attenuates Angiotensin II-Induced Endothelial Dysfunction In Vivo by Activating Akt

Abstract

Background: Endothelial dysfunction (ED) is a marker of vascular damage and a precursor of cardiovascular diseases such as hypertension, which involve inflammation and organ damage. Nitric oxide (NO), produced by eNOS, which is induced by pAKT, plays a crucial role in the function of a healthy endothelium. Methods: A combination of subfractions SF1 and SF3 (C4) of the aqueous fraction from Cucumis sativus (Cs-Aq) was evaluated to control endothelial dysfunction in vivo and on HMEC-1 cells to assess the involvement of pAkt in vitro. C57BL/6J mice were injected daily with angiotensin II (Ang-II) for 10 weeks. Once hypertension was established, either Cs-AqC4 or losartan was orally administered along with Ang-II for a further 10 weeks. Blood pressure (BP) was measured at weeks 0, 5, 10, 15, and 20. In addition, serum creatinine, inflammatory status (in the kidney), tissue damage, and vascular remodeling (in the liver and aorta) were evaluated. Cs-AqC4 was also tested in vitro on HMEC-1 cells stimulated by Ang-II to assess the involvement of Akt phosphorylation. Results: Cs-AqC4 decreased systolic and diastolic BP, reversed vascular remodeling, decreased IL-1β and TGF-β, increased IL-10, and decreased kidney and liver damage. In HMEC-1 cells, AKT phosphorylation and NO production were increased. Conclusions: Cs-AqC4 controlled inflammation and vascular remodeling, alleviating hypertension; it also improved tissue damage associated with ED, probably via Akt activation.