Synergistic Neuroprotective Effects of Traditional Chinese Medicine and Levodopa in Parkinson's Disease: A Behavioral and Pharmacokinetic Study

Parkinson's disease (PD) is a complex neurological disorder that causes debilitating motor symptoms such as tremors, rigidity, and bradykinesia. TCM formulations, such as Zhengan Xifeng Decoction (ZXFD) in combination with Western medicine (Levodopa), are being examined for Parkinson's disease treatment. However, the absence of reliable and interpretable experimental models has hampered mechanism elucidation. This study evaluated the neuroprotective effects of ZXFD in a rat model of PD, assessing its efficacy and safety when combined with Western medicine (WM). 240 mice with MPTP-induced PD-like symptoms were separated into two groups: the intervention group (IG, n = 120) got ZXFD + levodopa, and the control group (CG, n = 120) received only levodopa. Rotarod, open field, raised maze, Morris water maze, and tail suspension tests assessed motor function and cognitive performance after 12 weeks of therapy. Secondary outcome variables included ZXFD-Levodopa pharmacokinetic interactions and adverse event characteristics. Both treatment methods increase mouse motor function and cognitive functioning, as seen by improved scores on all behavioral tests. However, the ZXFD+ Levodopa group improved more significantly. Rotarod, Open Field, Morris water maze, and tail suspension scores improved significantly. We found significant ZXFD-Levodopa pharmacokinetic interactions in both groups. In the CG, Cmax was 150.9 ± 35.6 ng/mL, Tmax was 1.8 ± 0.5 h, AUC0-∞ was 654.2 ± 153.9 ng.h/mL, clearance was 23.4 ± 5.6 L/h, and half-life was 4.2 ± 1.0 h. In contrast, the IG showed a Cmax of 421.9 ± 93.5 ng/mL, Tmax of 3.2 ± 1.1 h, AUC0-∞ of 2431.9 ± 561.2 ng.h/mL, and clearance of 10.3 L/h, with reduced adverse events and mortality. According to this study, ZXFD + Levodopa could be a safe and effective treatment for Parkinson's disease-like symptoms. These findings indicate that this combined therapy strategy requires more clinical investigation to prove its efficacy and safety.