Immunomodulatory effect of Hawthorn extract in an experimental stroke model

Background: recently,we reported a neuroprotective effect for hawthorn (crataegus oxyacantha) ethanolic extract in middle cerebral artery occlusion-(mcao) induced stroke in rats. the present study sheds more light on the extract's mechanism of neuroprotection,especially its immunomodulatory effect.methods: after 15 days of treatment with hawthorn extract [100 mg/kg,pretreatment (oral)],male sprague dawley rats underwent transient mcao for 75 mins followed by reperfusion (either 3 or 24 hrs). we measured pro-inflammatory cytokines (il-1β,tnf-α,il-6),icam-1,il-10 and pstat-3 expression in the brain by appropriate methods. we also looked at the cytotoxic t cell sub-population among leukocytes (facs) and inflammatory cell activation and recruitment in brain (using a myeloperoxidase activity assay) after ischemia and reperfusion (i/r). apoptosis (tunel),and bcl-xl- and foxp3- (tregmarker) positive cells in the ipsilateral hemisphere of the brain were analyzed separately using immunofluorescence.results: our results indicate that occlusion followed by 3 hrs of reperfusion increased pro-inflammatory cytokine and icam-1 gene expressions in the ipsilateral hemisphere,and that hawthorn pre-treatment significantly (p ≤ 0.01) lowered these levels. furthermore,such pre-treatment was able to increase il-10 levels and foxp3-positive cells in brain after 24 hrs of reperfusion. the increase in cytotoxic t cell population in vehicle rats after 24 hrs of reperfusion was decreased by at least 40% with hawthorn pretreatment. in addition,there was a decrease in inflammatory cell activation and infiltration in pretreated brain. hawthorn pretreatment elevated pstat-3 levels in brain after i/r. we also observed an increase in bcl-xl-positive cells,which in turn may have influenced the reduction in tunel-positive cells compared to vehicle-treated brain.conclusions: in summary,hawthorn extract helped alleviate pro-inflammatory immune responses associated with i/r-induced injury,boosted il-10 levels,and increased foxp3-positive tregsin the brain,which may have aided in suppression of activated inflammatory cells. such treatment also minimizes apoptotic cell death by influencing stat-3 phosphorylation and bcl-xl expression in the brain. taken together,the immunomodulatory effect of hawthorn extract may play a critical role in the neuroprotection observed in this mcao-induced stroke model. © 2010 elango and devaraj; licensee biomed central ltd.