Ana Helena De Castro Dal Forno

Co-nanoencapsulation of antimalarial drugs increases their in vitro efficacy against Plasmodium falciparum and decreases their toxicity to Caenorhabditis elegans

&NA; Drugs used for the treatment and prevention of malaria have resistance‐related problems, making them ineffective for monotherapy. If properly associated, many of these antimalarial drugs may find their way back to the treatment regimen. Among the therapeutic arsenal, quinine (QN) is a second‐line treatment for uncomplicated malaria but has side effects that limit its use. Curcumin (CR) is a natural compound with anti‐plasmodial activities and low bioavailability. In this context, the aim of this work was to develop and characterize co‐encapsulated QN+CR‐loaded polysorbate‐coated polymeric nanocapsules (NC‐QC) to evaluate their activity on Plasmodium falciparum and the safety of the nanoformulations for Caenorhabditis elegans. NC‐QC displayed a diameter of approximately 200nm, a negative zeta potential and a slightly basic pH. The drugs are homogeneously distributed in the NCs in the amorphous form. Co‐encapsulated NCs exhibited a significant reduction in P. falciparum parasitemia, better than QN/CR. The worms exposed to NC‐QC showed higher survival and longevity and no decrease in their reproductive capacity compared to free and associated drugs. It was possible to prove that the NCs were absorbed orally by the worms using fluorescence microscopy. Co‐encapsulation of QN and CR was effective against P. falciparum, minimizing the toxic effects caused by chronic exposure of the free drugs in C. elegans. Graphical abstract: Symbol. No Caption available. Highlights:Quinine and curcumin loaded P80‐coated PCL nanocapsules was developed as a strategy against monotherapy‐resistant malaria.Polymeric walls protect quinine and curcumin from ultraviolet‐induced degradation.The co‐encapsulation of quinine and curcumin depicted antimalarial effects on the W2 and 3D7 Plasmodium falciparum strains.Quinine + curcumin‐loaded nanocapsules minimized the toxic effects of free drugs in Caenorhabditis elegans.

Purple pitanga fruit (Eugenia uniflora L.) protects against oxidative stress and increase the lifespan in Caenorhabditis elegans via the DAF-16/FOXO pathway

Pitanga, a fruit of the pitangueira tree (Eugenia uniflora L.), is native to Brazil and has a high antioxidant capacity due to the elevated amount of anthocyanins. The present study aimed to investigate the chemical composition of the purple pitanga fruit and to evaluate its antioxidant effect in the nematode Caenorhabditis elegans. We observed that the ethanolic extract of purple pitanga did not cause any toxic effects but notably increased worm lifespan. The extract improved the survival, reproduction and lifespan of the worms in pre- and post-exposure to stressors H2O2 and juglone, as well as improved the lifespan of the oxidative stress hypersensitive strain mev-1. Notably, PPE extract decreased reactive oxygen species by DCF-DA probe and protein carbonyl content from worms stressed with H2O2. The extract also affected the expression of superoxide dismutase SOD-3 and heat shock protein HSP-16.2 levels, daf 16 target genes that modulate lifespan and antioxidant metabolism. In addition, we demonstrate that these effects are dependent on DAF-16, as PPE extract did not provide protection in daf-16 mutants. Therefore, these results suggest that PPE significantly protected against oxidative stress modulating daf-16 target genes.