Innovation Research Institute of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China.
Innovation Research Institute of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China.
Redox Biol. 2024 Oct;76:103324. doi: 10.1016/j.redox.2024.103324. Epub 2024 Aug 20.
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.
小胶质细胞的极化表型在帕金森病（PD）的进展中至关重要。能够将小胶质细胞极化为 M2 表型的分子代表了一类有前途的抗 PD 药物化合物。Z-当归内酯（ZLG）是一种具有多种药理特性的天然存在的烯醇酯，尤其是在神经保护方面。我们首次研究了 ZLG 对抗 PD 的作用，并阐明了其潜在机制。结果主要表明，ZLG 可减轻小鼠的运动功能障碍，并防止黑质中多巴胺能神经元的丢失。在机制上，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。总之，我们的研究表明，ZLG 通过改变小胶质细胞极化和通过 Nrf2-TrxR 轴恢复氧化还原平衡，是一种有前景的 PD 治疗候选药物。
