Lifespan extension in caenorhabditis elegans by oxyresveratrol supplementation in hyper-branched cyclodextrin-based nanosponges.

Matencio, Adrián; Alejandra Guerrero-Rubio, M; Caldera, Fabrizio; Cecone, Claudio; Trotta, Francesco; García-Carmona, Francisco; Manuel López-Nicolás, José

In this work, the increase of the Caenorhabditis elegans (C.elegans) lifespan extension using hyper-branched cyclodextrin-based nanosponges (CD-NS) complexing oxyresveratrol (OXY), and the possible inhibition of C.elegans phosphodiesterase type 4 (PDE4) were evaluated. The titration displacement of fluorescein was used to calculate the apparent complexation constant (KF) between CD-NS and OXY. Moreover, PDE4 was expressed in E.coli, purified and refolded in presence of cyclodextrins (CDs) to study its possible inhibition as pharmacological target of OXY. The apparent activity was characterized and the inhibitory effect of OXY on PDE4 displayed a competitive in vitro inhibition corroborated in silico. A maximum increase of the in vivo life expectancy of about 9.6% of using OXY/CD-NS complexes in comparison with the control was obtained, in contrast to the 6.5 % obtained with free OXY. No effect on lifespan or toxicity with CD-NS alone was found. These results as a whole represent new opportunities to use OXY and CD-NS in lifespan products.