Chinese Journal of Tissue Engineering Research ›› 2025, Vol. 29 ›› Issue (30): 6466-6473.doi: 10.12307/2025.917

Previous Articles     Next Articles

Protective effects and mechanisms of 3-N-butylphthalide in Parkinson’s disease cell models

Zhang Xin1, Guo Baojuan2, Xu Huixin1, Shen Yuzhen1, Yang Xiaofan3, Yang Xufang1, Chen Pei1   

  1. 1Department of Pathophysiology, School of Basic Medicine, Mudanjiang Medical University, Mudanjiang 157011, Heilongjiang Province, China; 2Department of Pathology, Baotou Mongolian Medicine and Traditional Chinese Medicine Hospital, Baotou 014000, Inner Mongolia Autonomous Region, China; 3Department of Rehabilitation Medicine, Hongqi Hospital Affiliated to Mudanjiang Medical University, Mudanjiang 157011, Heilongjiang Province, China
  • Received:2024-09-10 Accepted:2024-11-26 Online:2025-10-28 Published:2025-03-28
  • Contact: Chen Pei, Associate professor, Master’s supervisor, Department of Pathophysiology, School of Basic Medicine, Mudanjiang Medical University, Mudanjiang 157011, Heilongjiang Province, China
  • About author:Zhang Xin, MS, Department of Pathophysiology, School of Basic Medicine, Mudanjiang Medical University, Mudanjiang 157011, Heilongjiang Province, China Guo Baojuan, MS, Department of Pathology, Baotou Mongolian Medicine and Traditional Chinese Medicine Hospital, Baotou 014000, Inner Mongolia Autonomous Region, China Zhang Xin and Guo Baojuan contributed equally to this article.
  • Supported by:
    Basic Scientific Research Business Expense Project of Provincial Colleges and Universities in Heilongjiang, No. 2023-KYYWF-0936 (to CP)

Abstract: BACKGROUND: D1-3-n-butylphthalide has antioxidant and anti-inflammatory effects and has been explored to have protective role in Parkinson’s disease, but the underlying mechanisms are unknown.
OBJECTIVE: To investigate the protective effect of D1-3-n-butylphthalide by the approach of network pharmacology, molecular docking, and cellular experimental validation.
METHODS: (1) Network pharmacology and molecular docking: The database was used to screen the targets of D1-3-n-butylphthalide and Parkinson’s disease. The intersection was taken from the construction of the target protein interaction network, and then screen the core targets. The GO and KEGG pathway enrichment was used to further analyze the core targets. The interaction between the target proteins and D1-3-n-butylphthalide was verified by molecular docking. (2) Cell validation: The passage 6 PC12 cells were divided into six groups for culture. The control group was cultured with conventional culture medium. The model group was cultured with N-methyl-4-phenylpyridinium iodide to induce Parkinson’s disease model. The ML385 inhibitor group was added with nuclear factor E2-related factor 2 inhibitor ML385 on the basis of inducing Parkinson’s disease model. The D1-3-n-butylphthalide treatment group was added with butylphthalide on the basis of inducing Parkinson’s disease model. The D1-3-n-butylphthalide combined with ML385 treatment group was added with D1-3-n-butylphthalide and ML385 on the basis of inducing Parkinson’s disease model. The D1-3-n-butylphthalide group was cultured with conventional culture medium containing butylphthalide alone. Cell proliferation, intracellular reduced glutathione and malondialdehyde levels, and protein expression of protein kinase B/glycogen synthase kinase 3β/nuclear factor E2-related factor 2 (AKT/GSK-3β/Nrf2) signaling pathway were detected.
RESULTS AND CONCLUSION: (1) A total of 52 targets were screened for the intersection of drugs and disease targets, and the core targets including the matrix metalloproteinase 9 and GSK-3β were involved the phosphatidylinositol 3-kinase (PI3K)/AKT and oxidative stress-related signaling pathways. The molecular docking binding energy of D1-3-n-butylphthalide and GSK-3β was -18.27 kJ/mol, which indicated that D1-3-n-butylphthalide had a good binding ability with GSK-3β. (2) Compared with the model group, the PC12 cell activity and reduced glutathione level in the D1-3-n-butylphthalide treatment group were increased (P < 0.05), the malondialdehyde level was decreased (P < 0.05), and the expression of p-AKT, p-GSK-3β, Nu-Nrf2, and T-Nrf2 proteins was increased (P < 0.05). Compared with the D1-3-n-butylphthalide group, the PC12 cell activity and reduced glutathione level in the D1-3-n-butylphthalide combined with ML385 treatment group were decreased (P < 0.05), the malondialdehyde level was increased (P < 0.05), and the expression of Nu-Nrf2 and T-Nrf2 proteins was decreased (P < 0.05). (3) These results demonstrate that D1-3-n-butylphthalide can inhibit oxidative stress and improve cell activity through the AKT/GSK-3β/Nrf2 signaling pathway, and has a protective effect on the Parkinson’s cell model induced by N-methyl-4-phenylpyridinium iodide.

Key words: network pharmacology, molecular docking, Parkinson’s disease, D1-3-n-butylphthalide, oxidative stress, signaling pathway, engineered tissue construction

CLC Number: