Protection of dauricine and daurisoline on PC12 cells damaged by glutamate or Aβ_25-35

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_25-35in vitro. Dauricine and daurisoline have the potential to treat AD effectively and have further research value.