Myricetin and Berberine Combination Ameliorates Brain Damage Induces by Cerebral Ischemia/Reperfusion Injury in Rats

Abstract

Background: Cerebral  ischemic/reperfusion  (I/R)injurymayresultin  considerable tissuedamageviainductionofinflammatorymediatorsandoxidativestressinbrain tissue.Theaimofthepresentstudy wastoinvestigatevalueofusingcombinedmyricetin plus berberinetreatmentinprotection againstshort-term globalcerebralI/Rinjuryin rats. MaterialandMethods:Thirty sixWistar-albinoratswereenrolledinthestudy,divided intofourgroupsincluding Shamgroup,I/Rgroup,I/R+(control-vehicle DMSO)andI/R+ myricetin  50  mg/kgplus  berberine5  mg/kginjectedintraperitoneally1  hourbefore inductionof ischemia. Measurementof braintissueIL-1β,ICAM- 1, caspase-3, Notch 1 andJagged1wasdoneafteronehourofreperfusioninadditiontotheassessmentof brain infarcted areaand histopathologicaltissue analysis.

Results:MyricetinandberberinecombinationattenuatesthecerebralI/Rinjury induced increase  in  inflammatory   cytokine  (IL-1β),  adhesion  molecule  (ICAM-1)  and proapoptotic enzyme (caspase-3).Additionally,itreducesthe size of infarcted area and histopathologicaldamage.However,suchprotectiveeffectwasnotfoundtobe mediated by Notch1signalingpathwaybecausedrugstreatmentdidn’tshowanychangesinthe increased levels of Notch1 and Jagged 1 seen in brain withI/Rinjury.

Conclusions:Myricetinandberberine combinationhasa neurocytoprotectiveoutcome againstcerebralI/Rinjurywhichismanifestedasanti-inflammatory anti-apoptoticeffect thatpreservedcellstructure andviability,neverthelessthiseffectisnotmediatedthrough Notch 1 signalingpathway.