The Association of Palmitoylethanolamide with Luteolin Decreases Autophagy in Spinal Cord Injury

Spinal cord injury (SCI) is a devastating condition of the central nervous system (CNS) often resulting in severe functional impairment and for which there are not yet restorative therapies. In the present study, we performed a widely used model of SCI to determine the neuroprotective propriety of palmitoylethanolamide (PEA) and the antioxidant effect of a flavonoid luteolin (Lut), given as a co-ultramicronized compound co-ultraPEALut. In particular, by western blot analysis and immunofluorescence staining, we investigated whether this compound (at the dose of 1 mg/kg) was able to modulate autophagy. Our results showed that treatment with co-ultraPEALut after SCI reduced the expression of proteins promoter of autophagy such as Beclin-1 and microtubule-associated protein 1A/1B-light chain 3 (MAP-LC3). In contrast, this compound decreased the levels of mammalian target of rapamycin (mTOR), p-Akt, and p-70S6K which are proteins that inhibit autophagy. These data confirmed that the protective role of co-ultraPEALut is associated with inhibition of excessive autophagy and regulation of protein degradation. Therefore, treatment with co-ultraPEALut could be considered as a possible therapeutic approach in an acute traumatic lesion like SCI.