GAPT regulates cholinergic dysfunction and oxidative stress in the brains of learning and memory impairment mice induced by scopolamine

Abstract

Background Cholinergic dysfunction and oxidative stress are the crucial mechanisms of Alzheimer's disease (AD). GAPT, also called GEPT (a combination of several active components extracted from the Chinese herbs ginseng, epimedium, polygala and tuber curcumae) or Jinsiwei, is a patented Chinese herbal compound, has been clinically widely used to improve learning and memory impairment, but whether it can play a neuroprotective role by protecting cholinergic neurons and reducing oxidative stress injury remains unclear. Methods Male ICR mice were intraperitoneally injected with scopolamine (3 mg/kg) to establish a learning and memory disordered model. An LC‐MS method was established to study the chemical compounds and in vivo metabolites of GAPT. After scopolamine injection, a step‐down passive‐avoidance test (SDPA) and a Y maze test were used to estimate learning ability and cognitive function. In addition, ELISA detected the enzymatic activities of acetylcholinesterase (AChE), acetylcholine (ACh), choline acetyltransferase (ChAT), malondialdehyde (MDA), glutathione peroxidase (GPX), and total superoxide dismutase (T‐SOD). The protein expressions of AChE, ChAT, SOD1, and GPX1 were observed by western blot, and the distribution of ChAT, SOD1, and GPX1 was observed by immunohistochemical staining. Results After one‐half or 1 month of intragastric administration, GAPT can ameliorate scopolamine‐induced behavioral changes in learning and memory impaired mice. It can also decrease the activity of MDA and protein expression level of AChE, increase the activity of Ach, and increase activity and protein expression level of ChAT, SOD, and GPX in scopolamine‐treated mice. After one and a half month of intragastric administration of GAPT, echinacoside, salvianolic acid A, ginsenoside Rb1, ginsenoside Rg2, pachymic acid, and beta asarone could be absorbed into mice blood and pass through BBB. Conclusions GAPT can improve the learning and memory ability of scopolamine‐induced mice, and its mechanism may be related to protecting cholinergic neurons and reducing oxidative stress injury.

Effect of ivabradine on cognitive functions of rats with scopolamine-induced dementia

“…Inflammation and oxidative stress occur before the cardinal neuropathological signs of Alzheimer's disease 25 . In the present study, we got similar results to those of Liu and his colleagues who reported that Sco treated mice showed increase content of MDA level and a significant decrease in the content of SOD in memory impaired mice 26 . We also recorded a significant decrease in TAC level in the hippocampus of the ES group.…”

Sea Cucumber-Derived Peptide Attenuates Scopolamine-Induced Cognitive Impairment by Preventing Hippocampal Cholinergic Dysfunction and Neuronal Cell Death

“…51,52 At medium and higher doses, FYDWPK showed an increased level of SOD and a decreased level of MDA in mouse serum and a reduced level of MDA in mouse hippocampal homogenates. Liu et al 17 reported that Jinsiwei alleviated the reduction in SOD activity compared to that in the model group and up-regulated SOD protein expression in the hippocampus of scopolamine-treated mice. A previous report by Foyet et al 53 also showed that the Emilia coccinae extract significantly improved the cognitive dysfunction in scopolamine-stimulated rats by relieving oxidative stress and inhibiting AChE activity.…”

“…Furthermore, it also increased ACh levels. 17 MDA, a secondary end-product of lipid peroxidation, is widely regarded as a biomarker of oxidative damage. 18 The fruit extract of Spondias mombin attenuated MDA levels in the hippocampus of mice with scopolamine-induced dementia and decreased lipid peroxidation levels.…”

Neuroprotective Potentials of Panax Ginseng Against Alzheimer’s Disease: A Review of Preclinical and Clinical Evidences

“…Ninjin-yoei-to (NYT), a formula containing 14 herbs, can promote the production of nerve growth factor in rat embryo astrocytes after incubation for 24 h ( Yabe et al, 2003 ). Additionally, GAPT (Jinsiwei), a combination of several active components, can reduce the AChE activity and expression and increase ACh synthesis to improve cholinergic nerve function, reducing the learning and memory impairments in scopolamine-induced mice ( Liu et al, 2020 ). Pretreatment with P. montana and red ginseng extracts significantly reduces catalase and AChE activities, inhibiting trimethyltin-induced neuronal cell death, oxidative stress, and learning and memory impairments ( Seo et al, 2018 ).…”