## 3 Pharmacological Properties of GP
### Neuroprotective Effect
#### 3.4.3 Anti-Parkinson's Disease
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 MPTP+-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 MPTP-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 \hline \end{tabular}
\end{table} 
Table 3: Anti-Parkinson’s disease effect of GP. had reported that GP could ameliorate L-DOPA-induced adverse effects and might be developed as a useful agent for adjuvant therapeutics of PD receiving long-term treatment with L-DOPA. GPS (25 and 50 mg/kg) and GPE (50 mg/kg) could effectively attenuate the development of L-DOPA-induced-dyskinesia without compromising the anti-Parkinson effects of L-DOPA by reducing \(\Delta\)FosB expression and ERK1/2 phosphorylation in the 6-hydroxyopamine (6-OHDA)-lesioned rat model of PD [92]. Studies showed that MPTP-lesioned mice exhibited deficits associated with habit learning and spatial memory, which were further aggravated by treatment with L-DOPA (25 mg/kg). However, treatment with GPS (50 mg/kg) ameliorated memory deficits via increasing the activation of the dopaminergic neuronal system and modulating the phosphorylation of the N-methyl-D-aspartate (NMDA) receptor-mediated signaling system [93]. In addition, GPS (50 mg/kg) and GPE (50 mg/kg) improved the symptoms of anxiety disorders in the MPTP-lesioned rat model of PD with or without L-DOPA treatment [94].