Morroniside and Salidroside attenuate ferroptosis through the Nrf2/GPX4 pathway in In Vivo and In Vitro models of Parkinson’s disease
學生姓名:
陳宇寧
指導教授:
林家媛
學期:
114下
摘 要:
Parkinson’s disease (PD) is closely associated with oxidative stress, mitochondrial dysfunction, and ferroptosis. Recent studies have indicated that the nuclear factor erythroid 2-related factor 2/glutathione peroxidase 4 (Nrf2/GPX4) pathway plays a critical role in oxidative stress regulation. This study integrates two articles to investigate the neuroprotective mechanisms of salidroside (SAL) and morroniside (MOR) against oxidative stress, mitochondrial dysregulation, and ferroptosis. In C57BL/6 mice, treatment with the neurotoxin 1-methyl-4-phenyl17 1,2,3,6-tetrahydropyridine (MPTP) induced PD-like pathological changes, including decreased Nrf2 expression, dysregulation of ferroptosis-related proteins, lipid peroxide accumulation, increased iron deposition in the substantia nigra, reduced tyrosine hydroxylase (TH) expression, dopaminergic neuronal damage, and motor dysfunction. MOR treatment alleviated MPTP-induced neuronal injury, upregulated Nrf2 expression, and restored ferroptosis-related protein expression, suggesting that MOR may exert neuroprotective effects by regulating Nrf2 signaling and inhibiting ferroptosis. In SH-SY5Y neuronal cells, erastin-induced ferroptosis caused iron and α-synuclein accumulation, decreased TH and ferroptosis-related protein expression, elevated oxidative stress markers, and decreased cell viability. SAL treatment increased the protein expression of Nrf2, GPX4, and SLC7A11, whereas the Nrf2 inhibitor ML385 attenuated these protective effects, indicating that SAL may improve erastin-induced cellular injury by regulating Nrf2 expression. Overall, SAL and MOR may protect dopaminergic neurons by modulating Nrf2-related signaling, thereby reducing neurotoxin-induced oxidative stress and ferroptosis. Therefore, salidroside and morroniside may serve as potential adjunctive therapeutic strategies for slowing the progression of PD
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