Qingkailing (QKL) is a well-known composite extract used in traditional Chinese medicine. This extract has been extensively administered to treat the acute phase of cerebrovascular disease. Our previous experiments confirmed that QKL exerts an inhibitory effect on cerebral ischemia-induced inflammatory responses. However, whether QKL suppresses the activation of microglia, the primary resident immune cells in the brain, has yet to be determined. In this study, BV2 microglial cells were used to validate the protective effects of QKL treatment following ischemia-reperfusion injury simulated via hypoxia/reoxygenation in vitro. Under these conditions, high expression levels of ROS, COX-2, iNOS, and p-p38 protein were detected. Following ischemia/reperfusion injury, QKL significantly increased the activity of BV2 cells to approximately the basal level by modulating microglial activation via inhibition of inflammatory factors, including TNF-α, COX-2, iNOS, and p-p38. However, QKL treatment also displayed dose-dependent differences in its inhibitory effects on p38 phosphorylation and inflammatory factor expression.
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.
A number of studies have shown that early-stage Alzheimer’s disease (AD) is associated with abnormal brain glucose metabolism before cognitive decline, which may be the key pathological change of asymptomatic AD. The pathogenesis of AD in traditional Chinese medicine is kidney deficiency and turbid phlegm. Based on this, GAPT (a mixture of herbal extracts) was made to invigorate kidney Yang and eliminate phlegm. Previous studies have shown that GAPT can improve and delay the memory decline, but the specific therapeutic target of AD in an early stage has not been studied. The aim of this study was to investigate the effect of GAPT on glucose metabolism in the early stage of AD. Eighty-eight 3-month-old male APP/PS1 transgenic mice were randomly divided into model group; donepezil group; and low, middle and high GAPT dosage groups. Twelve 3-month-old C57BL/6J mice were used as a control group. The Morris water maze test and the Step-Down Passive-Avoidance test were used to evaluate learning and memory ability. Cerebral extraction and the accumulation of glucose were scanned with a micro-positron-emission tomography (PET) imaging system. Immunohistochemistry, western blot analysis and polymerase chain reaction (PCR) were used to detect the expression of the PI3K/AKT-mTOR signalling pathway–related proteins and messenger RNAs (mRNAs) in hippocampus of APP/PS1 transgenic mice after 3 months of drug administration. GAPT can shorten the escape latency and error numbers compared to the model group. In micro-PET imaging analysis, GAPT can increase the glucose uptake average rate in the frontal lobe, temporal lobe, parietal lobe and hippocampus. The immunohistochemistry, western blot analysis and PCR results indicated that GAPT can increase the expression of PI3K, AKT, GLUT1 and GLUT3 in the hippocampus of APP/PS1 transgenic mice. In summary, GAPT can improve brain glucose metabolism damage in APP/PS1 transgenic mice, mainly by increasing brain glucose uptake, increasing glucose transport and improving the insulin signalling pathway.
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