Therapeupic Effects And Mechanisms Of Madecassoside On Parkinson's Diease By Chronic Rotenone Intoxication In Rats

Objective: To investigate the therapeupic effects of MC, the major active component of traditional Chinese herd'Centella asiatica', on the Parkinson's disease(PD) induced by the chronic rotenone intoxication in rats and further explore its possible protective mechanisms in the PD therapy of MC.Methods: The rats were divided into model group, Selegiline group, MC(10, 20 and 40 mg.kg-1.d-1) groups and normal control group randomly. PD models of rats were produced by rotenone(1mg.kg-1.d-1) injected subcutaneous in back for 30 days, and 10 days after rotenone exposure , MC or Selegiline were administrated by gavage for 40 days continuously in treated groups. Then, the effects of different MC dosage and Selegiline on the following parameters were evaluated by behavioral, biochemical, pathological and immunohistochemical methods, which were behavioral alterations related to motor function,biochemical alterations including levels of dopamine (DA) in striatum , levels of malonic dialdehyde(MDA) and activities of superoxide dismutase(SOD) and monoamine oxidase-B(MAO-B) in substentia nigra and striatum, pathological alterations and quantity of nerve cells(and nerve fibers) with the tyrosine hydroxylase(TH)-immunoreactivity in substentia nigra and striatum, protein expression of monoamine oxidase-B(MAO-B) in substentia nigra and striatum, as well as the expression of heme oxygenase-1(HO-1) protein and HO-1 mRNA in substentia nigra.Results: It was observed that rats in PD model group developed obvious motor dysfunction (including the decrease of the scores in the traction test and the angles in the inclined plane method,as well as the prolongation of the remove latency in the catalepsy test) (P<0.05),which was associated with an decrease in the levels of DA in striatum(P<0.05) and a loss of nerve cells and nerve fibers with the tyrosine hydroxylase-immunoreactivity in substentia nigra and striatum(P<0.05). Meanwhile,the levels of MDA increased and activities of SOD degraded in substentia nigra and striatum(P<0.05), simultaneously the expression of HO-1 mRNA and protein increased obviously in substentia nigra(P<0.05). However, the activity and protein expression of MAO-B were not influenced markedly, compared to the normal control group. Treatment with MC(20mg.kg-1) or Selegiline(0.7mg.kg-1) could remarkably increase the scores in the traction test and the angles in the inclined plane method(P<0.05), shorten the remove latency in the catalepsy test(P<0.05) ,and reduce the loss of nerve cells and nerve fibers with the tyrosine hydroxylase-immunoreactivity in substentia nigra and striatum induced by chronic rotenone exposure(P<0.05). The elevations of MDA levels and degression of SOD activity in substentia nigra and striatum were significantly reversed after treatment with MC or Selegiline(P<0.05). Moreover, the expression of HO-1 mRNA and protein in substentia nigra , induced by chronic rotenone exposure, was also attenuated by treatment with MC(20mg.kg-1) or Selegiline(P<0.05). Additionally, MC(40mg.kg-1) and Selegiline(0.7mg.kg-1) could notably inhibit the activities of MAO-B in substentia nigra and striatum, and increase the levels of DA in striatum(P<0.05).Conclusions: The results suggest that the MC could protect dopaminergic neurons in substentia nigra and ameliorate the motor dysfunction in Parkinson's disease induced by chronic rotenone exposure in rats,and its mechanisms might involve in enhancing anti-oxidant capacity , down regulating the expression of HO-1 mRNA and protein, and inhibiting the activities of MAO-B.