| Parkinson's disease(PD) is an adult-onset progressive neurodegenerative disorder. Neuropathological hallmarks of the disease include the degeneration and loss of dopaminergic neurons in the substantia nigra(SN) and the subsequent dopamine(DA) depletion in the striatum.Although the causes of PD are not known,amounting evidence demonstrate that oxidative stress plays a key role in the pathogenesis of PD. In PD patients,individual dopaminergic neuron showed increased iron levels compared to the control.Rosmarinic acid(RA) is a naturally occurring polyphenolic compound firstly exacted from Rosmarinius officinalis in 1958,which has a variety of biological functions including but not limited to anti-oxidative,free radical scavenging and metal ions chelating activities.However,whether RA could have neuroprotective effects on dopaminergic cells is still unknown.Using flow cytometry and spectrophotometry,in the present study we investigated the role of RA on 6-OHDA-induced oxidative stress in MES23.5 cells.The mechanisms underlying the role of RA were also investigated.The results were as follows:1.100μmol/L 6-OHDA treatment resulted in a significant decrease of cell viability (P＜0.01).10-4,10-5 mol/L RA pretreatment for 24 h could abolish the effects (P＜0.05).There was no difference in different concentrations of RA pretreated group.2.Compared with DMEM/F12 alone,a significant increase of 6-OHDA auto-oxidation rate was observed not only in DMEM/F12 containing 6-OHDA(100μmol/L) but also in DMEM/F12 containing both 6-OHDA(100μmol/L) and RA (10-4,10-5 mol/L)(P＜0.01).There is no difference between DMEM/F12 containing 6-OHDA(100μmol/L) and DMEM/F12 containing both 6-OHDA(100μmol/L) and RA(10-4,10-5 mol/L)(P＞0.05).3.100μmol/L 6-OHDA treatment resulted in a reduction of the mitochondrial transmembrane potential(Δψm) and an increase in reactive oxide species(ROS) generation(P＜0.01).10-4,10-5 mol/L RA pretreatment for 24 h could abolish the effects(P＜0.05).There was no difference in different concentrations of RA pretreated group.4.Compared with the control,a significant decrease of OD 510 nm was observed in RA(10-4～10-2mol/L),which showed RA could chelate iron in a concentration-dependent manner(P＜0.01).5.Iron treatment resulted in a reduction of theΔψm and an increase in ROS generation in MES23.5 cells(P＜0.01).While pretreated with 10-4,10-5 mol/L RA could partly abolish the effects(P＜0.05),There was no difference in different concentrations of RA pretreated group.The above results suggest that RA pretreatment could partially reverse intracellular ROS generation and theΔψm decrease induced by 6-OHDA or iron.These results put powerful evidence to the protective effects of RA on dopaminergic neurons injury in PD and further show some light on the development of potential clinical approaches. |
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