Anti-inflammatory Mechanism Of Oleoylethanolamide And The Neuroprotection Of Its Nano Dosage Form

Background:Ischemic stroke is a series of diseases which are triggered by some blocked cerebral vessels.It has become one of the three most awkward diseases since its high mortality,endlessly increasing morbidity,disability rate and lacking of therapeutic measures.Patients who are suffering ischemic stroke may acquire normal blood supplies through therapeutic or spontaneous reperfusion.However,the injuries brought by reperfusion exhibit more severe.Thus,to research and develop drugs aimed at this reperfusion is more urgent.Some researchers have demonstrated that oleoylethanolamide(OEA)decreased volumes of cerebral infarction,edema,destruction of blood-brain barrier and apoptosis triggered by reperfusion,which might be relative to the activation of peroxisome proliferators-activated receptors-a(PPARa).Some other researches have indicated that activated PPARa inhibited several crucial inflammatory signaling pathways such as NF-κB.In addition,large numbers of reports have manifested inflammation was one of the most considerable damage mechanisms during the acute period of reperfusion after ischemic stroke.Nanoparticles,as one of the most famous new dosage forms,possess numerous advantages that traditional ones do not owing to its mesoscopic effect produced by nanoscale,in which improved oral bioavailability is involved.By chance,there is one trouble,namely oral bioavailability,undoubtedly restricting the approaching to clinical application of OEA.Fortunately,in theory of chemical structure,OEA would probably tend to react with soybean lecithin(SPC),which is one kind of phospholipids that brings no side effect to the human body,to become nano-sized OEA-SPC phytosome,through which the awful oral bioavailability might be ameliorated.Aims:1.To explore if OEA could exhibit anti-inflammatory actions against reperfusion after ischemic stroke.2.To explore if the characteristics of OEA-SPC phytosome we need showed up and if the nanoparticle of OEA performed better on the treatment of reperfusion after ischemic stroke than traditional OEA.Methods:1.In the study of anti-inflammatory mechanism of OEA,all procedures was in parallel.We obstructed middle cerebral arteries(MCAO)for 1.5 hours on PPARa gene knocked out mice and normal ones then reperfusion was carried out.3 days after that,we detected the expressive quantities of inflammatory and anti-inflammatory cytokines,besides,the phenotypic transformation of microglia cells which are crucial to inflammation in cerebrum.2.In the innovative study of OEA-SPC phytosome,we used several classical methods to prepare some solid material that might be nano-sized OEA-SPC phytosome.After that,we detected if the characteristics of OEA-SPC phytosome we needed had shown up via several pharmaceutical methods about observing the qualities of nanoparticles,then made a compare between OEA-SPC phytosome and pure OEA on the neuroprotective efficacy of reperfusion after MCAO.Results:1.OEA inhibited the expression of inflammatory cytokines while promoted the secretion of anti-inflammatory cytokines that may perform functions relative to nerve regeneration via activating PPARa to protect cerebrum from acute injuries of reperfusion of MCAO.Last but not the least,The conclusion mentioned above was likely to be in much connection with the phenotypic transformation of M1 microglia cells to M2 microglia cells.2.1n OEA-SPC phytosome,hydrogen bonds existed between OEA and SPC.Meanwhile,particle sizes,zeta potential,sustained effect and stability is suitable,which also made the phytosome exhibited better treatment than traditional OEA.Conclusions:1.OEA activated PPARa to transform M1 to M2,so that an anti-inflammatory effect came out.2.There were characteristics on OEA-SPC phytosome we needed and OEA-SPC phytosome performed better on the treatment of reperfusion after ischemic stroke than traditional OEA.