Protection of dauricine and daurisoline on PC12 cells damaged by glutamate or Aβ25-35

IF 2.7 4区医学 Q3 NEUROSCIENCES

Brain Research Pub Date : 2025-04-02 DOI:10.1016/j.brainres.2025.149609

Xiao-Han Ma , Hui Dai , Song-Yao Liu , Xiao-Na Liu , Jing Zhang , Xue-Lian Meng

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引用次数: 0

Abstract

Glutamate (Glu) excitotoxicity and amyloid-β (Aβ) deposition are significant factors in the occurrence and development of Alzheimer’s disease (AD). Dauricine and daurisoline are two alkaloid components of Menispermum dauricum DC. that have a protective effect on the nervous system. The protection of dauricine and daurisoline on Glu-injured PC12 cells and the protection dauricine on Aβ_25-35-injured PC12 cells were investigated in this study. The results of the study demonstrated that on PC12 cells damaged by Glu (20 mM), dauricine and daurisoline (3 and 10 μM) increased the cell viability, reduced cell apoptosis, and enhanced mitochondrial membrane potential (MMP) levels. Dauricine and daurisoline can also reduce the levels of intracellular ROS and free Ca²⁺, and suppression the expression of CaM, p-CaMKII, and p-Tau in Glu-damaged PC12 cells. In addition, on PC12 cells damaged by Aβ_25-35 (30 μM), dauricine (3 and 10 μM) can also significantly increase the cell viability and MMP levels, inhibit cell apoptosis, reduce intracellular ROS and free Ca²⁺ levels, and down-regulate protein expression of CaM, p-CaMKII, and p-Tau. This study demonstrates for the first time that dauricine and daurisoline may inhibit the excessive phosphorylation of Tau protein and subsequent cell apoptosis by suppressing the Ca²⁺-CaM/CaMKII pathway, thereby protecting PC12 cells damaged Glu or Aβ_25-35 in vitro. Dauricine and daurisoline have the potential to treat AD effectively and have further research value.

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谷氨酸（Glu）兴奋毒性和淀粉样蛋白-β（Aβ）沉积是阿尔茨海默病（AD）发生和发展的重要因素。金丝桃碱和金丝桃碱是金丝桃（Menispermum dauricum DC.）的两种生物碱成分，对神经系统具有保护作用。本研究探讨了金丝桃碱和金丝桃碱对 Glu 损伤的 PC12 细胞的保护作用，以及金丝桃碱对 Aβ25-35 损伤的 PC12 细胞的保护作用。研究结果表明，在受到 Glu（20 mM）损伤的 PC12 细胞中，金丝桃碱和金丝桃碱（3 μM 和 10 μM）能提高细胞活力，减少细胞凋亡，提高线粒体膜电位（MMP）水平。去甲乌头碱和去甲乌头碱还能降低细胞内 ROS 和游离 Ca2+ 的水平，抑制 Glu 损伤的 PC12 细胞中 CaM、p-CaMKII 和 p-Tau 的表达。此外，在受到Aβ25-35（30 μM）损伤的PC12细胞中，金丝桃碱（3 μM和10 μM）也能显著提高细胞活力和MMP水平，抑制细胞凋亡，降低细胞内ROS和游离Ca2+水平，下调CaM、p-CaMKII和p-Tau的蛋白表达。本研究首次证明，去甲乌头碱和去甲乌头碱可通过抑制 Ca2+-CaM/CaMKII 通路，抑制 Tau 蛋白的过度磷酸化和随后的细胞凋亡，从而保护体外受损的 Glu 或 Aβ25-35 PC12 细胞。Dauricine和daurisoline具有有效治疗AD的潜力，具有进一步的研究价值。

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来源期刊

Brain Research 医学-神经科学

CiteScore

5.90

自引率

3.40%

发文量

268

审稿时长

47 days

期刊介绍： An international multidisciplinary journal devoted to fundamental research in the brain sciences. Brain Research publishes papers reporting interdisciplinary investigations of nervous system structure and function that are of general interest to the international community of neuroscientists. As is evident from the journals name, its scope is broad, ranging from cellular and molecular studies through systems neuroscience, cognition and disease. Invited reviews are also published; suggestions for and inquiries about potential reviews are welcomed. With the appearance of the final issue of the 2011 subscription, Vol. 67/1-2 (24 June 2011), Brain Research Reviews has ceased publication as a distinct journal separate from Brain Research. Review articles accepted for Brain Research are now published in that journal.