Aqueous Bark Extract of Ceiba speciosa (A. St.-Hill) Ravenna Protects against Glucose Toxicity in Caenorhabditis elegans.

Plants are widely used in folk medicine because of their pharmacological properties. Ceiba speciosa, popularly known as paineira-rosa or tree-of-wool, is a species found in the Northwest of Rio Grande do Sul, being native of the upper Uruguay River, Brazil. The tea obtained from the stem bark is employed in folk medicine to reduce cholesterol, triacylglycerides, and glucose levels. However, there are no studies in the literature proving its efficacy or the safety of its use. For this study, we used Caenorhabditis elegans as an animal model considering its advantages for risk assessment and pharmacological screenings. For the toxicological tests, C. elegans N2 (wild type) was treated with the aqueous extract of the stem bark of C. speciosa (ECE) at the first larval stage (L1) at concentrations of 5, 25, 50, and 250 µg/mL. To evaluate biological activities, we challenged the extract for oxidative stress resistance in the presence of paraquat (0.5 mM), H2O2 (1 mM), and against glucose-induced toxicity. Our results demonstrated that ECE did not alter survival rate, pharyngeal pumping, and reproduction of the nematodes. The extract was not able to protect the nematodes against the toxicity induced by prooxidants. Notably, ECE protected against glucotoxicity by increasing worms' life span and by reducing glucose levels. On the other hand, ECE treatment did not reduce lipid accumulation induced by exogenous glucose feeding, as observed in worms which lipid droplets were tagged with GFP. Based on our results, we believe that the extract is indeed promising for further studies focusing on carbohydrates metabolism; however, it needs to be carefully evaluated since the extract does not seem to modulate lipid accumulation.

Organoselenotriazoles attenuate oxidative damage induced by mitochondrial dysfunction in mev-1 Caenorhabditis elegans mutants.

Organic selenium compounds have several pharmacological activities already described, as anti-inflammatory and antitumor activities, which have been attributed to their antioxidant effects. Because they are promising in pharmacology, the synthesis of these compounds has increased significantly. As many new molecules are synthesized the use of a simple model like Caenorhabditis elegans is highly advantageous for initial evaluation of the toxicity and therapeutic potential of these molecules. The objective of this study was to evaluate the toxicity and antioxidant capacity of a series of selenotriazoles compounds in C. elegans. The animals were exposed to the compounds in liquid medium for only 30 min at the first larval stage (L1). The compounds had no toxic effects at the concentrations tested. Treatment with selenotriazoles (10 µM) partially reversed the stress induced by the pesticide paraquat (1 mM). Se-Tz Ia compound partially increased the survival of worms treated with H2O2 (0.5 mM). The compounds also increased the longevity of mev-1 mutants, which have a reduced life span by the production of excessive reactive oxygen species (ROS) in the mitochondria caused by a mutation in complex II of the electron transport chain. In addition, the compounds reduced the levels of ROS determined by the fluorescent probe DCF-DA as well as also reduced catalase enzyme activity in these animals. Based on the results found, it is possible to conclude that the compounds have antioxidant activity mainly in oxidative stress condition generated by a mitochondrial dysfunction in C. 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.

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

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 200 nm, 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.