铁凋亡是一种铁依赖性细胞死亡形式,其特征是活性氧(ROS)过度生成和脂质过氧化。杨梅素,一种存在于许多植物中的类黄酮,表现出强大的抗氧化能力。鉴于铁积累和ROS引起的多巴胺能神经元死亡是帕金森病(PD)的两个主要病理标志,我们的目的是研究杨梅素是否通过抑制铁性凋亡来减少神经元死亡。通过向大鼠腹腔注射1-甲基-4-苯基-1,2,3,6-四氢吡啶(MPTP)和用1-甲基-4-苯基吡啶(MPP)处理SH-SY5Y细胞建立PD模型,分别。通过评估Fe2+的水平来鉴定铁凋亡,ROS,丙二醛(MDA),和谷胱甘肽(GSH)。结果表明,杨梅素治疗可有效缓解MPTP引发的运动障碍,多巴胺神经元死亡,PD模型中α-突触核蛋白(α-Syn)的积累。杨梅素还能缓解MPTP诱导的铁凋亡,正如Fe2+水平降低所证明的那样,ROS,PD模型中黑质(SN)和血清中MDA和GSH水平升高。所有这些变化都被erastin逆转了,铁性凋亡激活剂.体外,杨梅素处理可恢复SH-SY5Y细胞活力,减轻MPP+-诱导的SH-SY5Y细胞铁凋亡。机械上,杨梅素在MPP+处理的SH-SY5Y细胞中加速核因子E2相关因子2(Nrf2)和随后的谷胱甘肽过氧化物酶4(Gpx4)表达的核转位,铁性凋亡的两种关键抑制剂。总的来说,这些数据表明,杨梅素可能是通过抑制PD中铁凋亡而降低多巴胺能神经元死亡的潜在药物。
Ferroptosis is an iron-dependent cell death form characterized by reactive oxygen species (ROS) overgeneration and lipid peroxidation.
Myricetin, a flavonoid that exists in numerous plants, exhibits potent antioxidant capacity. Given that iron accumulation and ROS-provoked dopaminergic neuron death are the two main pathological hallmarks of Parkinson\'s disease (PD), we aimed to investigate whether myricetin decreases neuronal death through suppressing ferroptosis. The PD models were established by intraperitoneally injecting 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) into rats and by treating SH-SY5Y cells with 1-methyl-4-phenylpyridinium (MPP+), respectively. Ferroptosis was identified by assessing the levels of Fe2+, ROS, malondialdehyde (MDA), and glutathione (GSH). The results demonstrated that
myricetin treatment effectively mitigated MPTP-triggered motor impairment, dopamine neuronal death, and α-synuclein (α-Syn) accumulation in PD models.
Myricetin also alleviated MPTP-induced ferroptosis, as evidenced by decreased levels of Fe2+, ROS, and MDA and increased levels of GSH in the substantia nigra (SN) and serum in PD models. All these changes were reversed by erastin, a ferroptosis activator. In vitro,
myricetin treatment restored SH-SY5Y cell viability and alleviated MPP+-induced SH-SY5Y cell ferroptosis. Mechanistically,
myricetin accelerated nuclear translocation of nuclear factor E2-related factor 2 (Nrf2) and subsequent glutathione peroxidase 4 (Gpx4) expression in MPP+-treated SH-SY5Y cells, two critical inhibitors of ferroptosis. Collectively, these data demonstrate that myricetin may be a potential agent for decreasing dopaminergic neuron death by inhibiting ferroptosis in PD.