Gynostemma pentaphyllum extract ameliorates motor dysfunc-tion in mouse Parkinson's disease model through inhibiting neuronal apoptosis.

Objectives: To investigate the protective effects and underlying mechanisms of Gynostemma pentaphyllum extract on motor dysfunction in mouse model of Parkinson's disease (PD).

Methods: Eighty C57BL/6 male mice were randomly divided into five groups: control group, PD model group, levodopa treatment group (positive control group), low-dose GP treatment group (LD-GP group), and high-dose GP treatment group (HD-GP group), with 16 mice per group. The PD model was induced by injection of 6-hydroxydopamine into the substantia nigra pars reticulata in mice of last 5 groups. Two weeks after 6-hydroxydopamine modeling, mice in positive control group received introperitoneal injection of levodopa 10 mg·kg^－1·d^－1, mice in LD-GP and HD-GP groups received oral 100 mg·kg^－1·d^－1 or 200 mg·kg^－1·d^－1 for 3 weeks, respectively. After 3-week-treatment, the effects of GP on motor dysfunction in 6-OHDA-induced PD mice were assessed using open field and CatWalk gait tests, while the effects on muscle strength were evaluated by forelimb grip strength. Immunofluorescence staining was used to detect the number of tyrosine hydroxylase (TH) positive neurons. The levels of dopamine and serotonin in midbrain were determined by enzyme-linked immunosorbent assay. In addition, Western blotting was performed to detect the expression of mitogen-activated protein kinase (MAPK) family proteins such as p- extracellular signal-regulated kinase (ERK)1/2, p-p38 and p-c-Jun N-terminal kinase (JNK)1/2 , and mitochondrial apoptosis pathway proteins such as B-cell lymphoma (Bcl)-2, Bcl-2 associated X protein (Bax), and cleaved- cysteine aspartic acid specific protease (caspase)-3.

Results: Behavioral experiments showed that GP significantly improved the spontaneous activity and motor coordination of PD mice (P<0.05). And the forelimb grip strength was also increased by GP treatment (P<0.05), compared with PD model group. In addition, compared with model group, the number of TH-positive neurons in substantia nigra pars reticulata region, the levels of dopamine and serotonin in midbrain and the expression of p-ERK1/2 were significantly increased by GP treatment (all P<0.05), whereas the expression of p-p38 and p-JNK1/2, the ratio of Bax/Bcl-2 and cleaved-caspase 3/caspase 3 were significantly decreased (all P<0.05).

Conclusions: The results indicate that GP might increase dopamine and serotonin levels in midbrain and promoted the survival of dopaminergic neurons in substantia nigra pars reticulata by regulating the expression of phosphorylation of MAPK family proteins and the expression of mitochondrial apoptosis-related proteins, and then ameliorate motor deficits in PD mice.