CGA ameliorates cognitive decline by regulating the PI3K/AKT signaling pathway and neurotransmitter systems in rats with multi-infarct dementia

Abstract

Multi infarct dementia (MID) is a form of dementia that is preventable and treatable. However, at present, the drugs used in MID treatment were developed for Alzheimer's disease. While only a limited range of drugs is available, the incidence of MID is increasing year on year. The present study aimed to investigate the effect and underlying mechanisms of a combination of ginsenosides and astragalosides (CGA) on cognitive decline in rats with MID. A rat model of MID was established using micro-thromboembolism, and the behavioral changes in the rats were evaluated using the Morris water maze and open field tests at 60 days post-CGA intervention. The pathological morphology of the hippocampal CA1 area was observed using hematoxylin and eosin staining. The contents of ATP, ADP and AMP were determined using high-performance liquid chromatography. Mitochondrial swelling and changes in the membrane potential in the hippocampus were detected using flow cytometry, and the changes in insulin, glutamate and γ-aminobutyric acid (GABA) content were detected using ELISA. Additionally, the expression of PI3K and AKT proteins was detected using western blot analysis. In a rat model of MID, CGA shortened the escape latency, increased the frequency of platform crossing, improved the disordered vertebral cell arrangement and reduced the cell number in the hippocampal CA1 area. CGA also reduced the degree of mitochondrial swelling, increased the mitochondrial membrane potential, and elevated the energy load and ATP content in the brain of rats with MID. Furthermore, CGA increased the insulin content and upregulated the expression of PI3K and AKT in the brain of rats with MID. In addition, in the rat model of MID, CGA also enhanced the movement time and the frequency of standing, and decreased the concentration of glutamate and GABA in the brain tissue. Amelioration of the cognitive decline in rats with MID by CGA was associated with its regulatory effect on the PI3K/AKT signaling pathway and neurotransmitter systems.

Characterization and Duodenal Transcriptome Analysis of Chinese Beef Cattle With Divergent Feed Efficiency Using RNA-Seq

“…Studies have demonstrated that the MAPK signaling pathway is associated with lipid (Wang et al, 2018;Zhang et al, 2018) and energy metabolism (Zheng et al, 2016;Kim et al, 2018) that regulates glucose metabolism (Long et al, 2015). Moreover, studies have also shown that PI3K-Akt signaling is involved in glucose (Ruzzi et al, 2020), lipid (Fu et al, 2020), and energy metabolism [79,80]. Based on the present results of the enrichment analysis, it appears that the identified DEGs may regulate feed efficiency through signaling pathways related to energy metabolism and substance metabolism.…”

Breviscapine restores sevoflurane-induced cognitive dysfunction by activating the PI3K/Akt pathway and inhibiting NF-κB

“…In addition to the effects of breviscapine on apoptosis, inflammation, and oxidative stress, we observed its influence on PI3K/Akt and NF-κB pathways. A combination of ginsenosides and astragalosides was verified to improve cognitive impairment in rats with multi-infarct dementia through regulation of PI3K/Akt pathway (Fu et al, 2020).…”

Roles of traditional chinese medicine regulating neuroendocrinology on AD treatment

“…TCM also reduces neuronal apoptosis and loss of neurons caused by excessive autophagy ( 34 , 35 ). Beyond that, TCM can improve the pathways related to memory storage, and relieve the symptoms of memory loss by protecting the normal energy metabolism of the brain, restoring the structure and function of synapses and restoring neurotransmitter related neurotransmission ( 36 , 37 ).…”