Studies On Protective Effects Of Catalpol In Models For Parkinson's Disease

The apoptotic model of Parkinson's disease in vitro was made by 1-methyl-4-phenylpyridinium ion (MPP+) in PC12 cells and the apoptotic mechanism was analyzed in mitochondria-dependent caspase cascade. At the early stage of MPP+ treatment, over-expression of Bax and the leakage of cytochrome c (cyt-c) from mitochondria to cytosol were confirmed. The cytosolic cyt-c released into extracellular space at the late stage by membrane leakage as determined by release of LDH. Addition of cyt-c accelerated to viability loss of apoptotic cell suggesting a pro-apoptotic role of cyt c released into the culture medium. Caspase-3 also was activated in the late stage of MPP+-application. It suggested that MPP+-induced apoptosis was involved in mitochondria-dependent caspase cascade.The three kinds of iridoids played different roles on hydrogen peroxide (H2O2)-and MPP+-induced viability loss. Gentiopircrin had not any protective effect while geniposide might enhance toxic role. Catalpol inhibited loss of cell viability in H2O2-and MPP+-induced PC12 cells. The above results indicated that substituent groups of iridoids might play role on cell loss.Catalpol could inhibit apoptosis by mitochondria-dependent caspase cascade in MPP+-induced PC12 cells. MPP+ suppressed appearance of morphological changes and apoptotic bodies. The mechanism was involved in that catalpol not only suppressed the up-regulation of Bax and the release of mitochondrial cytochrome c to cytosol, but also attenuated caspase-3 activation, and eventually protected against MPP+-induced apoptosis.In mice, the subacute application of neurotoxin 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP) could model Parkinson's disease with severe damage todopaminergic system. Pretreatment with catalpol (15 mg/kg) inhibited the reduction of tyrosine hydroxylase immunoreactivity (TH-ir) cells and of dopamine (DA) in midbrain, with improving of glutathione (GSH) level in midbrain and striatum. Pretreatment with catalpol (5 mg/kg) had no influence on DA and GSH content in midbrain and striatum of mice.