Yindan Xinnaotong Soft Capsule Ameliorates Parkinson’s Disease and is Associated with Modulation of the AKT/MDM2/p53 Pathway: Network Pharmacology, Molecular Docking, and Experimental Validation
Yulei Xia, Yifeng Zhang, Xiaolu Wang, Hang Yang, Shuai Hou, Hua Yang, yanqiang wangObjective:
Parkinson’s Disease (PD) is a progressive neurodegenerative disorder characterized by nigrostriatal dopaminergic neuronal loss, neuroinflammation, oxidative stress, and motor dysfunction. Current therapies mainly provide symptomatic relief, whereas effective disease-modifying strategies remain limited. Yindan Xinnaotong soft capsule (YDXNT), a multi-component Chinese patent medicine, has shown neuroprotective potential, but its pharmacological effects in PD remain insufficiently understood. This study aimed to investigate the neuroprotective effects of YDXNT and identify signaling pathways potentially involved in its actions against experimental PD-related pathology.
Methods:
Network pharmacology was used to identify candidate bioactive compounds, therapeutic targets, and enriched pathways of YDXNT in PD. Molecular docking was performed to predict interactions between representative compounds and core targets. The predicted mechanisms were further evaluated in vivo using MPTP-induced parkinsonian mice and in vitro using MPP+-treated BV-2 microglial cells. Behavioral testing, TH and Iba-1 staining, ELISA, RT-qPCR, and Western blotting were used to assess motor function, dopaminergic injury, microglial activation, neurotrophic factors, and pathway-related molecular changes.
Results:
Seven representative compounds—β-sitosterol, cryptotanshinone, isogoycyrol, isorhamnetin, kaempferol, luteolin, and quercetin—were prioritized as candidate bioactive constituents. PI3K, AKT, MDM2, and p53 were identified as core pathway-related targets, and molecular docking predicted favorable compound–target interactions, with binding energies below −6 kcal/mol. YDXNT improved motor performance, preserved TH-positive neurons and striatal fibers, and reduced Iba-1-positive microglial activation in MPTP-treated mice. High-dose YDXNT also increased BDNF, GDNF, and CDNF levels. In animal tissues and BV-2 cells, YDXNT increased PI3K and AKT phosphorylation and MDM2 expression while reducing p53 expression.
Discussion:
These findings suggest that YDXNT may exert neuroprotective effects through coordinated regulation of dopaminergic neuronal integrity, microglial activation, neurotrophic support, and cell-survival signaling. The convergence of network pharmacology, molecular docking, and experimental findings supports the possible involvement of the PI3K/AKT/MDM2/p53 signaling axis; however, the current evidence demonstrates association rather than pathway causality, and direct target engagement requires further validation.
Conclusion:
YDXNT ameliorates experimental PD-related pathology through multi-component and multi-target actions associated with the regulation of the PI3K/AKT/MDM2/p53 signaling axis, supporting its further investigation as a potential neuroprotective strategy for PD.