The effects of Olea europaea leaf extract (OLE) phenolics, including oleuropein (OL), hydroxytyrosol (HT), tyrosol (TYR), and rutin against glioblastoma (GB), independently and in combination with temozolomide (TMZ), were investigated in T98G and A172 cells. Cell growth was assessed by WST-1, real-time cell analysis, colony formation, and cell cycle distribution assays. A dual acridine orange propidium iodide (AO/PI) staining and annexin V assay determined cell viability. A sphere-forming assay, an intracellular oxidative stress assay, and the RNA expression of CD133 and OCT4 investigated the GB stem-like cell (GSC) phenotype. A scratch wound-healing assay evaluated migration capacity. OL was as effective as OLE in terms of apoptosis promotion (p < 0.001) and GSC inhibition (p < 0.001). HT inhibited cell viability, GSC phenotype, and migration rate (p < 0.001), but its anti-GB effect was less than the total effect of OLE alone. Rutin decreased reactive oxygen species production and inhibited colony formation and cell migration (p < 0.001). TYR demonstrated the least effect. The additive effects of OL, HT, TYR and rutin with TMZ were significant (p < 0.001). Our data suggest that OL may represent a novel therapeutic approach against GB cells, while HT and rutin show promise in increasing the efficacy of TMZ therapy.

Objective: Topical cytidine-5′-diphosphocholine (CDP-choline) improves functional recovery and promotes nerve regeneration in sciatic nerve injury in rats. The aims of this study were to test whether systemic treatment with CDP-choline was effective in improving the recovery of injured sciatic nerve, and to determine whether the cytidine and/or choline moieties of CDP-choline contribute to its beneficial actions. Methods: Seventy Sprague–Dawley rats underwent a surgical procedure that involved transectioning and immediate surgical repairing of the right sciatic nerve. Rats were assigned to one of five groups and administered intraperitoneally 1 ml/kg of saline (control) or saline containing 600 μmol/kg of each of CDP-choline, cytidine, choline, or cytidine+choline. Results: Recovery in sciatic function index score was greater in rats treated with CDP-choline, choline, or cytidine+choline at 8 and 12 weeks after the interventions. Peripheral nerve regeneration evaluated by electromyography at 12 weeks was also greater in rats receiving CDP-choline (228% of control), choline (168% of control), or cytidine+choline (221% of control). Axon counts and axon density increased significantly following CDP-choline, choline, or cytidine+choline, respectively. Treatment with equivalent dose of cytidine failed to affect sciatic function index, electromyography, and axon counts. Treatment with CDP-choline, but not its metabolites improved nerve adherence and separability score. Conclusion: These data show that intraperitoneal CDP-choline, as well as the combination of its metabolites, cytidine+choline, improves functional recovery and promotes regeneration of injured sciatic nerves in rats. CDP-choline also improves nerve adherence and separability.