Background:L-dopa(Levodopa)is well known for managing PD(Parkinson’s disease);however,its prolonged use caused dyskinesia(LID).Due to the varied presentation of LID,effective treatment options are scarce.Flavonoids r...Background:L-dopa(Levodopa)is well known for managing PD(Parkinson’s disease);however,its prolonged use caused dyskinesia(LID).Due to the varied presentation of LID,effective treatment options are scarce.Flavonoids reported their neuroprotective activity by ameliorating acetylcholinesterase,monoamine oxidase,and neuroinflammation.Kaempferol is anotherflavonoid bearing these potentials.Aim:To evaluate neuroprotective activity of kaempferol in dyskinetic rats.Methods:PD was developed in Sprague-Dawley rats by injecting combination of L-ascorbic acid(10µL)+6-OHDA(12µg)in medial forebrain bundle to induce neuronal damage in substantial nigra(SNr).LID was induced by administrating combination of L-dopa(20 mg/kg)+benserazide HCl(5 mg/kg)for 42 days.Rats were concomitantly treated with amantadine(40 mg/kg)or kaempferol(25,50,and 100 mg/kg,p.o.).Results:Kaempferol(50 and 100 mg/kg)markedly(p<0.05)inhibited LID-induced abnormal involuntary movements(AIMs)and alternation in motor function.Kaempferol administration considerably(p<0.05)inhibited reduced mitochondrial complex activities,serotonin and dopamine levels,Bcl-2,and Tyrosine hydroxylase protein expressions in SNr.Additionally,kaempferol considerably(p<0.05)attenuated increased cFOS,FosB,Parkin,and Pdyn mRNAs expressions,Bax,cleaved caspase-3,caspase-3,and pJNK proteins levels;DOPAC and 5-HIAA levels in SNr.A positive correlation was reported between cFOS,FosB,Parkin,Pdyn,apoptosis,and TH with AIMs.Conclusion:Kaempferol effectively attenuated L-dopa-induced AIMs and dyskinesia via amelioration of alterations in cFOS,FosB,Parkin,Pdyn,Tyrosine hydroxylase,and apoptosis in the brain SNr.展开更多
文摘Background:L-dopa(Levodopa)is well known for managing PD(Parkinson’s disease);however,its prolonged use caused dyskinesia(LID).Due to the varied presentation of LID,effective treatment options are scarce.Flavonoids reported their neuroprotective activity by ameliorating acetylcholinesterase,monoamine oxidase,and neuroinflammation.Kaempferol is anotherflavonoid bearing these potentials.Aim:To evaluate neuroprotective activity of kaempferol in dyskinetic rats.Methods:PD was developed in Sprague-Dawley rats by injecting combination of L-ascorbic acid(10µL)+6-OHDA(12µg)in medial forebrain bundle to induce neuronal damage in substantial nigra(SNr).LID was induced by administrating combination of L-dopa(20 mg/kg)+benserazide HCl(5 mg/kg)for 42 days.Rats were concomitantly treated with amantadine(40 mg/kg)or kaempferol(25,50,and 100 mg/kg,p.o.).Results:Kaempferol(50 and 100 mg/kg)markedly(p<0.05)inhibited LID-induced abnormal involuntary movements(AIMs)and alternation in motor function.Kaempferol administration considerably(p<0.05)inhibited reduced mitochondrial complex activities,serotonin and dopamine levels,Bcl-2,and Tyrosine hydroxylase protein expressions in SNr.Additionally,kaempferol considerably(p<0.05)attenuated increased cFOS,FosB,Parkin,and Pdyn mRNAs expressions,Bax,cleaved caspase-3,caspase-3,and pJNK proteins levels;DOPAC and 5-HIAA levels in SNr.A positive correlation was reported between cFOS,FosB,Parkin,Pdyn,apoptosis,and TH with AIMs.Conclusion:Kaempferol effectively attenuated L-dopa-induced AIMs and dyskinesia via amelioration of alterations in cFOS,FosB,Parkin,Pdyn,Tyrosine hydroxylase,and apoptosis in the brain SNr.
