The polarization phenotype of microglia is critical in the progression of Parkinson's disease (PD). Molecules that can polarize microglia toward the M2 phenotype represent a promising class of compounds for anti-PD medications. Z-ligustilide (ZLG) is a naturally occurring enol ester with diverse pharmacological properties, especially in neuroprotection. For the first time, we investigated the effect of ZLG on anti-PD and elucidated its underlying mechanism. The results primarily showed that ZLG attenuated motor deficits in mice and prevented the loss of dopaminergic neurons in the substantia nigra. Mechanistically, ZLG alleviates oxidative stress-induced apoptosis of microglia by triggering the endogenous antioxidant system. Besides, ZLG modulated phenotypic polarization of the microglia through the activation of the Nrf2-TrxR axis, leading to microglia polarization towards the M2 phenotype. Taken together, our research showed that ZLG is a prospective therapy candidate for PD by altering microglia polarization and restoring redox equilibrium through the Nrf2-TrxR axis.

中文翻译：

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Z-藁本内酯通过激活帕金森病小鼠模型中的 Nrf2-TrxR 轴来调节小胶质细胞的表型极化，从而提供神经保护作用


小胶质细胞的极化表型在帕金森病（PD）的进展中至关重要。能够使小胶质细胞极化为 M2 表型的分子代表了一类有前景的抗 PD 药物化合物。 Z-藁本内酯 (ZLG) 是一种天然存在的烯醇酯，具有多种药理特性，尤其是在神经保护方面。我们首次研究了 ZLG 的抗 PD 作用并阐明了其潜在机制。结果主要表明，ZLG 减轻了小鼠的运动缺陷，并防止黑质中多巴胺能神经元的损失。从机制上讲，ZLG 通过触发内源性抗氧化系统来减轻氧化应激诱导的小胶质细胞凋亡。此外，ZLG通过激活Nrf2-TrxR轴来调节小胶质细胞的表型极化，导致小胶质细胞向M2表型极化。总而言之，我们的研究表明，ZLG 通过改变小胶质细胞极化并通过 Nrf2-TrxR 轴恢复氧化还原平衡，成为 PD 的潜在治疗候选者。