目的 探究天麻提取物抗帕金森病（Parkinson’s disease，PD）的活性及作用机制。方法 基于1-甲基-4-苯基-1,2,3,6-四氢吡啶（1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine，MPTP）诱导的斑马鱼PD模型，以抗PD活性为筛选指标，对天麻提取物开展活性导向分离，借助网络药理学与qRT-PCR明确其最优活性部位及潜在机制。结果 天麻总水提物具有显著的抗PD活性，可改善PD样行为（P＜0.001），保护多巴胺能神经元与脑部血管（P＜0.05、0.01、0.001），并减少神经细胞凋亡（P＜0.05、0.01、0.001）。网络药理学发现其作用机制与磷脂酰肌醇3-激酶（phosphatidylinositol 3-kinase，PI3K）/蛋白激酶B（protein kinase B，Akt）信号通路密切相关。经大孔树脂分离纯化获得天麻总水提物不同洗脱部位，结合抗PD活性指标筛选，确定水部位、30%乙醇部位和95%乙醇部位为最优活性部位。超高效液相色谱-四极杆飞行时间质谱联用技术（ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry，UPLC-Q-TOF/MS）鉴定出最优活性部位中巴利森苷A、巴利森苷B、巴利森苷C、巴利森苷E、天麻素、蓖麻油酸、克罗酰胺7种关键活性单体，结合斑马鱼行为指标分析，推断天麻素和蓖麻油酸为抗PD活性最佳单体。结论 天麻提取物通过调节自噬、氧化应激和PD相关基因表达来发挥抗PD的作用。

Objective To explore the anti-Parkinson’s disease (PD) activity, optimal active parts, key components and molecular mechanism of Gastrodia elata extract. Methods Based on the zebrafish PD model induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), an induced zebrafish PD model was used, with anti-PD activity as the screening criterion, to perform activity-guided fractionation of G. elata extract. Network pharmacology and qRT-PCR were employed to identify its most active fraction and elucidate the underlying mechanisms. Results The total aqueous extract of G. elata had significant anti-PD activity, which could improve PD-like behaviors (P < 0.001), protect dopaminergic neurons and cerebral blood vessels (P < 0.05, 0.01, 0.001), and reduce neuronal apoptosis (P < 0.05, 0.01, 0.001). Network pharmacology revealed that its mechanism was closely related to the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway. Different elution fractions of the total aqueous extract of G. elata were obtained through macroporous resin separation and purification. Based on the screening of anti-PD activity indicators, the water fraction, 30% ethanol fraction and 95% ethanol fraction were determined as the optimal active fractions. Ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS) identified seven key active monomers, namely parishin A, parishin B, parishin C, parishin E, gastrodin, ricinoleic acid and crocinamide, in the optimal active fractions. Combined with the analysis of zebrafish behavioral indicators, it was inferred that gastrodin and ricinoleic acid were the best single monomer for anti-PD activity. Conclusion G. elata extract exerts its anti-PD effects by modulating the expressions of autophagy, oxidative stress and PD-related genes.

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国家重点研发计划项目（2026YFE0201900）；国家自然基金面上基金项目（82574783）；泰山学者青年专家项目（tsqn202312233）；山东第一医科大学（山东省医学科学院）临床-基础联合创新团队项目（202404）