Elmorsy Ekramy M, Al-Ghafari Ayat B, Al Doghaither Huda A, Elghareeb Mona M, Alsaqati Mouhamed
Center of Health Research, Northern Border University, 91431, Arar, Saudi Arabia.
Department of Biochemistry, Faculty of Science, King Abdulaziz University, 21589, Jeddah, Saudi Arabia.
J Mol Neurosci. 2025 Apr 8;75(2):46. doi: 10.1007/s12031-025-02342-7.
This study investigates the neuroprotective effects of fucoxanthinol (FXL) against the toxic activities of two compounds known to induce neurotoxic effects in humans and animals. MPTP (1-methyl- 4-phenyl- 1,2,3,6-tetrahydropyridine) induces Parkinson's disease (PD)-like phenotypes by inhibiting mitochondrial complex I in dopaminergic neurons. Chlorpyrifos (CPF), another neurotoxic agent, is associated with acute and long-term neurotoxicity primarily through acetylcholinesterase (AChE) inhibition. FXL demonstrated the ability to reverse the neurotoxic effects of CPF and MPTP in SH-SY5Y dopaminergic neuronal cell models. Treatment with FXL enhances mitochondrial function in SH-SY5Y cells exposed to CPF and MPTP, as demonstrated by increased levels of Adenosine triphosphate (ATP), mitochondrial membrane potential (MMP), mitochondrial complexes activities, and oxygen consumption rates, pyruvate dehydrogenase (PDH) activities, and mitophagy pathways. This improvement highlights FXL's ability to counteract the mitochondrial dysfunction induced by these neurotoxic agents. Additionally, FXL reduces oxidative damage and enhances cell viability. At the molecular level, the neuroprotective effects were also associated with the modulation of apoptotic cell markers, including Bcl- 2 and the oxidative damage markers. Molecular docking data further support the outcomes of our in vitro studies. Multivariable analysis highlights the neuroprotective effects of FXL. These findings indicate the potential of FXL to mitigate CPF- and MPTP-induced neurotoxicity, suggesting its promise as a therapeutic agent for managing neuronal damage observe in PD.
本研究调查了岩藻黄质醇（FXL）对两种已知可在人类和动物中诱导神经毒性作用的化合物的神经保护作用。1-甲基-4-苯基-1,2,3,6-四氢吡啶（MPTP）通过抑制多巴胺能神经元中的线粒体复合体I来诱导帕金森病（PD）样表型。另一种神经毒性剂毒死蜱（CPF）主要通过抑制乙酰胆碱酯酶（AChE）与急性和长期神经毒性相关。在SH-SY5Y多巴胺能神经元细胞模型中，FXL显示出逆转CPF和MPTP神经毒性作用的能力。用FXL处理可增强暴露于CPF和MPTP的SH-SY5Y细胞中的线粒体功能，这表现为三磷酸腺苷（ATP）水平升高、线粒体膜电位（MMP）、线粒体复合体活性、氧消耗率、丙酮酸脱氢酶（PDH）活性以及线粒体自噬途径增强。这种改善突出了FXL抵消这些神经毒性剂诱导的线粒体功能障碍的能力。此外，FXL可减少氧化损伤并提高细胞活力。在分子水平上，神经保护作用还与凋亡细胞标志物（包括Bcl-2）和氧化损伤标志物的调节有关。分子对接数据进一步支持了我们体外研究的结果。多变量分析突出了FXL的神经保护作用。这些发现表明FXL减轻CPF和MPTP诱导的神经毒性的潜力，表明其有望作为治疗帕金森病中观察到的神经元损伤的治疗剂。
