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

Summary

This pre-clinical study demonstrates that ZXFD and Levodopa safely and effectively improve motor skills and cognitive function in animal models of Parkinson's disease. Clinical research is necessary to confirm these findings and explore the potential of this therapy to alleviate symptoms and enhance life quality.

Abstract

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.

Introduction

Parkinson's disease (PD) represents a complex and multifactorial neurodegenerative disorder that impacts millions of individuals globally, exhibiting a prevalence of approximately 1% among those over the age of 60^1,2. This disorder is characterized by the progressive loss of dopamine-producing neurons in the substantia nigra, a region of the brain that plays a critical role in motor control³. The degeneration of these neurons results in a deficiency of dopamine, a neurotransmitter that regulates movement, motivation, and reward processing⁴. The motor symptoms of ....

Protocol

​All animal procedures were conducted in accordance with institutional guidelines and approved by the Animal Care and Use Committee of the Institutional Animal Care and Use Committee (2024-154) of Xi'an Hospital of Traditional Chinese Medicine Encephalopathy. The study adhered to established ethical principles for animal research.

1. Mice model

1. Acquire male C57BL/6 mice aged 8-10 weeks from a certified laboratory animal vendor. House the mice in a temperature-controlled environment set at 22 ± 2 °C. Maintain a 12 h light-dark cycle and ensure they have ad libitum access to food and water.

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Results

This study investigates the therapeutic efficacy of ZXFD in combination with Levodopa (WM) in a murine model of PD. A total of 240 mice exhibiting MPTP-induced PD-like symptoms were enrolled and randomly assigned to either the intervention group (IG, n = 120), which received ZXFD + Levodopa, or the control group (CG, n = 120), which received WM alone, as illustrated in Figure 1. Through Immunohistochemical Staining for Tyrosine Hydroxylase, it was found that .......

Discussion

Zhengan Xifeng Decoction serves as a TCM formula utilized in the treatment of PD and various neurodegenerative disorders. The formula comprises a combination of herbs, including ginseng, ginkgo biloba, and astragalus membranaceus, which are believed to work synergistically to alleviate PD symptoms^45,46. The ZXFD+ Levodopa combination therapy effectively reduces PD symptoms through several mechanisms. These actions encompass halting cell death and promoting neurog.......

Materials

List of materials used in this article

Name	Company	Catalog Number	Comments
Evaporator	Shanghai Linbel Instrument Co., Ltd	LB-EL-01
High-performance liquid chromatography (HPLC)	Shimadzu, Kyoto, Japan	LC-20AT
Levodopa	Xi'an Tian Guangyuan Biotech Co., Ltd (China)	TY-001
MPTP, or 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine	Sigma-Aldrich, Inc.,United States	M-102
Shimadzu LC Solution software	Shimadzu, Kyoto, Japan	https://www.sigmaaldrich.com/IN/en/product/sigma/m0896
Zhengan Xifeng Decoction (ZXFD)	Kamwo / Meridian Pro Formulas	SKU / MPF: MPF20131