SIRT1 Signaling Is Involved in the Vascular Improvement Induced by Moringa Oleifera Seeds during Aging

Vascular aging is linked to reduce NO bioavailability, endothelial dysfunction, oxidative stress, and inflammation. We previously showed that a 4-week treatment of middle-aged Wistar rats (MAWRs, 46 weeks old) with Moringa oleifera seed powder (MOI, 750 mg/kg/day) improved vascular function. Here, we investigated the involvement of SIRT1 in MOI-induced vascular improvement. MAWRs were treated with a standard or MOI-containing diet. Young rats (YWR, 16 weeks old) were the controls and received a standard diet. The hearts and aortas were harvested to evaluate SIRT1 and FOXO1 expression via Western blot and/or immunostaining, SIRT1 activity via a fluorometric assay, and oxidative stress using the DHE fluorescent probe. In the hearts and aortas, SIRT1 expression, reduced in MAWRs compared to YWRs, was enhanced in MOI MAWRs. In the hearts, SIRT1 activity did not differ between YWRs and MAWRs, whereas it was increased in MOI MAWRs compared with them. In the aortas, SIRT1 activity decreased in MAWRs, and it was similar in the MOI MAWRs and YWRs. FOXO1 expression increased in the nuclei of MAWR aortas compared to YWR and was reversed in MOI MAWRs. Interestingly, MOI treatment normalized oxidative stress enhanced in MAWRs, in both the heart and aorta. These results demonstrate the protective role of MOI against cardiovascular dysfunction due to aging via enhanced SIRT1 function and subsequently reduced oxidative stress

In-vitro and in-vivo antimalarial activity of caffeic acid and some of its derivatives.

OBJECTIVES: To explore the in-vitro and in-vivo antimalarial potential of caffeic acid and derivatives. METHODS: Two common phenolic acids (caffeic acid and chlorogenic acid) were evaluated for in-vitro and in-vivo antiplasmodial activity in comparison with some semi-synthetic derivatives that were synthesized. An in-vitro assay based on plasmodial lactate dehydrogenase activity, and the classical in-vivo 5-day suppressive test from Peters on an artemisinin-resistant Plasmodium berghei strain was used. Parasitic stage sensitivity to ethyl caffeate was determined in this work. KEY FINDINGS: Phenolic acid esters derivatives showed better antiplasmodial activity than corresponding phenolic acids. The derivative with the highest in-vitro activity being caffeic acid ethyl ester, exhibiting an IC50 = 21.9 +/- 9.4 mum. Ethyl caffeate and methyl caffeate were then evaluated for antimalarial activity in vivo and ethyl caffeate showed a growth inhibition of 55% at 100 mg/kg. Finally, it seems that ethyl caffeate blocks the growth of young parasitic forms. CONCLUSIONS: Our study provides evidence for an antimalarial potential of caffeic acid derivatives which are common in several medicinal plants traditionally used against malaria. It also demonstrates the possibility to use such derivatives in the treatment of malaria