Background:Local inflammation induced by microglial activation plays a significant role in the pathological process of cerebral ischemia.Angelica keiskei(Miq.)Koidz.,a traditional botanical drug,can be used as a diure...Background:Local inflammation induced by microglial activation plays a significant role in the pathological process of cerebral ischemia.Angelica keiskei(Miq.)Koidz.,a traditional botanical drug,can be used as a diuretic,laxative or galactagogue.Xanthoangelol(XA),an active chalcone compound from the aerial part of Angelica keiskei,has anti-inflammatory effects in the peripheral tissues.However,its effect against neuroinflammation is yet unclear.Objective:The present study aims to investigate whether XA could mitigate ischemic stroke damage through attenuating neuroinflammation due to microglia activation.Methods:Middle cerebral artery occlusion/reperfusion(MCAO/R)induced cerebral ischemia and oxygen-glucose deprivation/reperfusion(OGD/R)or lipopolysaccharide(LPS)-stimulated BV2 microglia cells were utilized to evaluate XA’s protection against ischemic injury and neuroinflammation.The severity of brain injury was assessed using 2,3,5-triphenyltetrazolium chloride(TTC)staining and neurological assessment.The expressions of inflam-matory cytokines were quantified by enzyme-linked immunosorbent assay(ELISA)and reverse transcription-polymerase chain reaction(RT-PCR).Reactive oxygen species(ROS)were assessed using dichlorodihydrofluores-cein diacetate(DCF-DA)staining.NF-κB p65 nuclear translocation was confirmed by immunofluorescence(IF)staining.The expressions of proteins were quantified by Western blotting.Results:XA was efficacious in reducing infarct size and improving neurological function in MCAO/R mice.In ischemic brain tissue,XA reduced microglial activation and proinflammatory cytokine expression.In lipopolysac-charide(LPS)and OGD/R-induced cell models,XA suppressed the production of ROS and decreased the secretion of inflammatory cytokines.Additionally,XA suppressed the nuclear translocation and phosphorylation of NF-κB p65 and blocked the activation of NLR family pyrin domain containing 3(NLRP3)inflammasome.The protec-tion of XA against MCAO/R-induced damages was not attenuated in TLR4^(−/−)and MD2^(−/−)mice.Mito-TEMPO treatment reversed XA’s anti-inflammatory properties in OGD/R-induced BV2 cells.Conclusion:XA attenuates ischemic stroke injury by suppressing microglial inflammatory responses.This efficacy is tied to its antioxidant activity and is independent of Toll-like receptor 4(TLR4)or myeloid differentiation protein 2(MD2).展开更多
文摘Background:Local inflammation induced by microglial activation plays a significant role in the pathological process of cerebral ischemia.Angelica keiskei(Miq.)Koidz.,a traditional botanical drug,can be used as a diuretic,laxative or galactagogue.Xanthoangelol(XA),an active chalcone compound from the aerial part of Angelica keiskei,has anti-inflammatory effects in the peripheral tissues.However,its effect against neuroinflammation is yet unclear.Objective:The present study aims to investigate whether XA could mitigate ischemic stroke damage through attenuating neuroinflammation due to microglia activation.Methods:Middle cerebral artery occlusion/reperfusion(MCAO/R)induced cerebral ischemia and oxygen-glucose deprivation/reperfusion(OGD/R)or lipopolysaccharide(LPS)-stimulated BV2 microglia cells were utilized to evaluate XA’s protection against ischemic injury and neuroinflammation.The severity of brain injury was assessed using 2,3,5-triphenyltetrazolium chloride(TTC)staining and neurological assessment.The expressions of inflam-matory cytokines were quantified by enzyme-linked immunosorbent assay(ELISA)and reverse transcription-polymerase chain reaction(RT-PCR).Reactive oxygen species(ROS)were assessed using dichlorodihydrofluores-cein diacetate(DCF-DA)staining.NF-κB p65 nuclear translocation was confirmed by immunofluorescence(IF)staining.The expressions of proteins were quantified by Western blotting.Results:XA was efficacious in reducing infarct size and improving neurological function in MCAO/R mice.In ischemic brain tissue,XA reduced microglial activation and proinflammatory cytokine expression.In lipopolysac-charide(LPS)and OGD/R-induced cell models,XA suppressed the production of ROS and decreased the secretion of inflammatory cytokines.Additionally,XA suppressed the nuclear translocation and phosphorylation of NF-κB p65 and blocked the activation of NLR family pyrin domain containing 3(NLRP3)inflammasome.The protec-tion of XA against MCAO/R-induced damages was not attenuated in TLR4^(−/−)and MD2^(−/−)mice.Mito-TEMPO treatment reversed XA’s anti-inflammatory properties in OGD/R-induced BV2 cells.Conclusion:XA attenuates ischemic stroke injury by suppressing microglial inflammatory responses.This efficacy is tied to its antioxidant activity and is independent of Toll-like receptor 4(TLR4)or myeloid differentiation protein 2(MD2).
