Extract of Cynomorium songaricum ameliorates mitochondrial ultrastructure impairments and dysfunction in two different in vitro models of Alzheimer’s disease

Abstract

Abstract Background Alzheimer’s disease (AD) is one of the most common neurodegenerative disorders, but there is still no effective way to stop or slow its progression. Our previous studies demonstrated that extract of Cynomorium songaricum (ECS), a Chinese herbal medicine, had neuroprotective effects in AD models in vivo. However, the pharmacological mechanism of ECS in AD is still unclear. Methods To study the mechanisms of action of the effects of ECS on AD, we used Aβ25–35- and H2O2-exposed HT22 cells to mimic specific stages of AD in vitro. The mitochondrial membrane potential (MMP), intracellular ATP, intracellular reactive oxygen species (ROS), and expression levels of mitochondrial dynamics-related proteins in each group were examined. Furthermore, we explored the mechanisms by which ECS reduces the phosphorylation of Drp1 at Ser637 and the changes in the concentrations of intracellular calcium ions in the two models after FK506 intervention. Results The results showed that ECS significantly enhanced the MMP (P < 0.05), increased intracellular ATP levels (P < 0.05) and decreased intracellular ROS levels in the Aβ- and H2O2-induced cell models (P < 0.05). Additionally, ECS regulated the expression levels of mitochondrial dynamics-related proteins by reducing the phosphorylation of Drp1 at Ser637 (P < 0.05) and decreasing the expression of Fis1 in the H2O2-induced models (P < 0.05). Further study indicated that ECS reduced the overload of intracellular calcium (P < 0.05). Conclusion Our study results suggest that ECS protects the mitochondrial ultrastructure, ameliorates mitochondrial dysfunction, and maintains mitochondrial dynamics in AD models.