Lei Tong, Fu Gaoshuang, Xue Xin, Yang Hongjun
Department of Disease and Syndromes Research, Institute of Basic Theory for Chinese Medicine, China Academy of Chinese Medical Sciences, Beijing, 100700, China.
Department of Disease and Syndromes Research, Institute of Basic Theory for Chinese Medicine, China Academy of Chinese Medical Sciences, Beijing, 100700, China.
Phytomedicine. 2025 May;140:156553. doi: 10.1016/j.phymed.2025.156553. Epub 2025 Feb 24.
Parkinson's disease (PD) is a complex and multifactorial disorder of the nervous system. Tianma Gouteng Decoction (TGD) is a clinical prescription of traditional Chinese medicine for PD, but its neuroprotective effects and mechanisms for PD are poorly understood.
The aim of this study was to explore the mechanism of TGD in the treatment of PD.
Serum pharmacochemistry, single cell sequencing, network pharmacology, and validation experiment were combined to study the effect of TGD in PD model.
TGD water extract and its distribution in serum of PD mice were analyzed by secondary metabolomics. The crossing blood-brain barrier components and targets were preliminarily identified. Target cells and pathways of TGD were analyzed by network pharmacology and single cell sequencing.
TGD treatment improved the movement disorders in MPTP-induced PD mice, restoring dopaminergic neurons in the substantia nigra region and suppressing the expression of α-synuclein. We identified 1272 components in TGD, among which 73 were distributed in the serum of PD mice after oral administration. Network pharmacological analysis demonstrated that these components were involved in the regulation of apoptosis, and 15 of them could across the blood-brain barrier and bind to PD pathological proteins. Single nucleus RNA sequencing analysis identified 18 cell subpopulations, and TGD treatment restored the neuron-oligodendrocyte crosstalk. Neurons were identified as the most widely responding target cells, while oligodendrocytes were the core response target cells to TGD therapy. After treatment, the apoptosis of oligodendrocytes was inhibited, and the secretion of trophic factor was enhanced, facilitating the improvement of neuronal synaptic plasticity and neuroinflammation.
This study systematically elucidates the molecular mechanism of TGD improving movement disorders, which is helpful to provide new ideas for drug development of PD.
帕金森病（PD）是一种复杂的多因素神经系统疾病。天麻钩藤饮（TGD）是治疗PD的一种临床中药方剂，但其对PD的神经保护作用及机制尚不清楚。
本研究旨在探讨TGD治疗PD的机制。
结合血清药物化学、单细胞测序、网络药理学及验证实验研究TGD在PD模型中的作用。
采用二次代谢组学分析TGD水提取物及其在PD小鼠血清中的分布。初步鉴定穿越血脑屏障的成分和靶点。通过网络药理学和单细胞测序分析TGD的靶细胞和途径。
TGD治疗改善了MPTP诱导的PD小鼠的运动障碍，恢复了黑质区域的多巴胺能神经元，并抑制了α-突触核蛋白的表达。我们在TGD中鉴定出1272种成分，其中73种在口服给药后分布于PD小鼠血清中。网络药理学分析表明，这些成分参与细胞凋亡的调控，其中15种可穿越血脑屏障并与PD病理蛋白结合。单核RNA测序分析鉴定出18个细胞亚群，TGD治疗恢复了神经元-少突胶质细胞的相互作用。神经元被确定为反应最广泛的靶细胞，而少突胶质细胞是TGD治疗的核心反应靶细胞。治疗后，少突胶质细胞的凋亡受到抑制，营养因子的分泌增加，促进了神经元突触可塑性和神经炎症的改善。
本研究系统阐明了TGD改善运动障碍的分子机制，有助于为PD的药物研发提供新思路。
