## 3 Pharmacological Properties of GP
### Neuroprotective Effect
#### 3.4.3 Anti-Parkinson's Disease  
Parkinson's disease (PD) is a chronic neurodegenerative disease, which mainly occurs in middle-aged and elderly patients. The main clinical manifestation included bradykinesia, static tremor, autonomic nerve dysfunction, and myotonia. To date, large amounts of studies had demonstrated the anti-Parkinson's property of GP, as shown in Table 3.  
Studies on the pathogenesis of PD had demonstrated that the loss of dopaminergic neurons in the brain of PD patients was closely related to oxidative stress [96]. The 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced decreases of glutathione content and SOD activity in the substantia nigra, which resulted in oxidative stress, loss of nigral dopaminergic neurons, and motor dysfunction, were all attenuated by treatment with GPS [90]. In vitro, GPS protected primary cultured dopaminergic neurons against 1-methyl-4-phenylpyridinium ion (MPP+)-induced oxidative injury as well. It was found that GPS pretreatment had stronger protective effect than GPS co-treatment or post-treatment [91]. L-3, 4-Dihydroxyphenylalanine (L-DOPA) was the natural precursor of dopamine and was the most effective therapy for PD. However, chronic L-DOPA administration resulted in a loss of drug efficacy and irreversible adverse effects including motor and non-motor dysfunctions in both patients with PD and animal models of PD [92; 93]. Several studies  
\begin{table}
\begin{tabular}{p{113.8 pt} p{113.8 pt} p{113.8 pt} p{113.8 pt}} \hline \hline
**Models** & **Medical Composition** & **Dosage** & **Activity/Mechanism** & **Ref. ** \\ \hline MPTP-induced rat model of PD & GPS & 100, 200, and 400 mg/kg, i.p. & Attenuated the motor deficits and striatal dopamine loss in a dose-dependent manner, increased the number of tyrosine hydrolase (TH)-immunopositive neurons, increased glutathione content, and enhanced SOD activity in the substantia nigra. & \\ \hline MPP+-induced oxidative injury of dopaminergic neurons & GPS & 50, 100, 200, 400 mg/mL in primary & Increased glutathione content, enhanced activity of GSH-Px and SOD, attenuated MMPP+-induced oxidative damage, reduction of dopamine uptake, loss of TH-immunopositive neurons and degeneration of TH-immunopositive neurites, and 200 mg/mL of GPS had the maximum protective effect. & \\ \hline
6-OHDA-induced rat model of PD & GPS and GP-EX for 22 days, p.o. & Attenuated the development of L-DOPA-induced dyskinesia without compromising the anti-parkinson effects of L-DOPA by modulating the biomarker activities of \(\Delta\)FosB expression and ERK1/2 phosphorylation. & \\ \hline MPTP-induced rat model of PD & GPS & 50 mg/kg for 21 days, p.o. & Improved the levels of TH-immunopositive cells and dopamine in the substantia nigra and striatum, suppressed NMDA receptor expression, and increased the phosphorylation of ERK1/2 and CREB in the 1 hippocampus, ameliorated deficits in habit learning and spatial memory by increasing the activation of the dopaminergic neuronal system and modulating NMDA receptor-mediated signaling systems. & \\ \hline MPTP-induced rat model of PD & GPS and GP-EX & GPS (50 mg/kg), GP-EX (50 mg/kg) for 21 days, p.o. & Improved the symptom of anxiety disorders by modulating the brain levels of dopamine and serotonin, increased the number of TH-immunopositive neuronal cells, and increased the density of dopamine neurons in the substantia nigra. & \\ \hline
6-OHDA-induced rat model of PD & GPS-EX & 10 mg/kg and 30 mg/kg for 28 days, p.o. & Therapy-induced decreases of glutathione content and SOD activity in the substantia nigra, which resulted in oxidative stress, loss of nigral dopaminergic neurons, and motor dysfunction, were all attenuated by treatment with GPS [90]. In vitro, GPS protected primary cultured dopaminergic neurons against 1-methyl-4-phenylpyridinium ion (MPP+)-induced oxidative injury as well. It was found that GPS pretreatment had stronger protective effect than GPS co-treatment or post-treatment [91].