Extract of Cynomorium songaricum ameliorates mitochondrial ultrastructure impairments and dysfunction in two different in vitro models of Alzheimer\u2019s disease

Dan Cheng,Xu Wang,Xinjie Li,Yi Lu,Lei Su,Lingling Li,Mengyuan Hu

doi:10.1186/s12906-021-03375-2

Abstract

BackgroundAlzheimer’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.MethodsTo 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.ResultsThe 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).ConclusionOur study results suggest that ECS protects the mitochondrial ultrastructure, ameliorates mitochondrial dysfunction, and maintains mitochondrial dynamics in AD models.

Highlights

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
Mitochondrial dysfunction affects the production of reactive oxygen species (ROS) [14]; the molecular targets regulated by ROS, including mitochondrial DNA, calcium homeostasis, mitochondrial dynamics and function, and energy homeostasis, are affected by mitochondrial dysfunction [15,16,17]
Regulatory effects of extract of Cynomorium songaricum (ECS) on mitochondrial dynamicsrelated proteins The results showed that the expression of dynamin-related protein 1 (Drp1) in the ECS group was significantly lower than that in the control group

Summary

Introduction

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. NFTs are formed by the misfolding of highly phosphorylated Tau protein, while SPs are formed mainly from the deposition of amyloid-beta (Aβ) peptides [1]. These misfolded protein aggregates have high neurotoxicity and synaptotoxicity, leading to a cascade of neurodegeneration during the progression of the disease [2]. Some researchers have argued that the hypothesis suggesting that Aβ directly causes AD may not be correct [4] They have proposed that focusing on the early stage of AD and implementing effective interventions are promising new treatment strategies [5]. Excessive ROS production exacerbates mitochondrial dysfunction, disrupts intracellular calcium balance, opens mitochondrial permeability transition pores (MPTPs), and leads to a decrease in mitochondrial membrane potential (MMP), thereby contributing to a vicious cycle [17, 18]

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Discussion

Conclusion