Effect of GAPT extract on expression of tau protein and its phosphorylation related enzymes in hippocampal neurons of APPV717I transgenic mice

Ni, Jingnian; Shi, Jing; Zhang, Xuekai; Yang, Yichang; Liu, Xiaomeng; Wei, Mingqing; Li, Ting; Wang, Pengwen; Tian, Jinzhou; Wang, Yongyan

doi:10.1007/s11655-017-2545-7

Cited by 3 publications

(3 citation statements)

References 28 publications

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“…In another study, GAPT can effectively reduce GSK‐3β expression level in the brain cortex of APPV7171 transgenic mice, thus playing a neuroprotective role (Shi et al, 2013). It also regulates the expression of CDK5 and PP2A in hippocampal neurons, thereby inhibiting abnormal tau phosphorylation (Ni et al, 2017). GAPT can increase APP/PS1 transgenic mice's brain glucose uptake and glucose transport and improve the insulin signaling pathway (Mana et al, 2019).…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2020

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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.

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Section: Introductionmentioning

confidence: 99%

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

et al. 2020

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“…GAPT, a mixed Chinese herbal extracts, has shown effectively decrease the level of GSK-3β expression and Aβ accumulation via the inhibition of γ-secretase (presenilin-1) and promoting insulin degrading enzyme (IDE) and neprilysin (NEP) in APPV717I transgenic mice [ 16 , 17 ]. Other possible mechanisms also have been explored [ 18 , 19 ]. Based on these previous studies, GRAPE granule with analogous activity and active components to GAPT may make additional benefits to AD patients with the treatment of donepezil or memantine.…”

Section: Discussionmentioning

confidence: 99%

“…A possible explanation for this phenomenon is that donepezil targets at the neurotransmitter level, a downstream rather than upstream effector of pathophysiological processes of AD. Herbal medicine, on the other hand, targets broadly, including Aβ accumulation, neuroinflammation, tau hyperphosphorylation, glucose metabolism dysregulation, harmful gut microbiota, oxidative stress, and other factors that play important roles in the onset and progression of AD [ 16 – 19 , 22 , 23 ].…”

Section: Discussionmentioning

confidence: 99%

Adding Chinese herbal medicine to conventional therapy brings cognitive benefits to patients with Alzheimer’s disease: a retrospective analysis

Shi

et al. 2017

BMC Complement Altern Med

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BackgroundConventional therapy (CT) such as donepezil and memantine are well-known short-term treatments for the symptoms of Alzheimer’s disease (AD). The efficacy of them, however, drops below baseline level after 9 months. In China, herbal therapy as a complementary therapy is very popular. Should conventional therapy combined with herbal therapy (CT + H) make add-on benefit?MethodsIn this retrospective cohort study, 344 outpatients diagnosed as probable dementia due to AD were collected, with the treatment of either CT + H or CT alone in clinical settings. All the patients were examined with coronary MRI scan. Cognitive functions were obtained by mini–mental state examination (MMSE) every 3 months with the longest follow-up of 24 months.ResultsMost of the patients were initially diagnosed with mild (MMSE = 21–26, n = 177) and moderate (MMSE = 10–20, n = 137) dementia. At 18 months, CT+ H patients scored on average 1.76 (P = 0.002) better than CT patients, and at 24 months, patients scored on average 2.52 (P < 0.001) better. At 24 months, the patients with improved cognitive function (△MMSE ≥ 0) in CT + H was more than CT alone (33.33% vs 7.69%, P = 0.020). Interestingly, patients with mild AD received the most robust benefit from CT + H therapy. The deterioration of the cognitive function was largely prevented at 24 months (ΔMMSE = −0.06), a significant improvement from CT alone (ΔMMSE = −2.66, P = 0.005).ConclusionsCompared to CT alone, CT + H significantly benefited AD patients. A symptomatic effect of CT + H was more pronounced with time. Cognitive decline was substantially decelerated in patients with moderate severity, while the cognitive function was largely stabilized in patients with mild severity over two years. These results imply that Chinese herbal medicines may provide an alternative and additive treatment for AD.

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Efficacy of Chinese herbal compound GAPT for the treatment of Alzheimer’s disease during mouse/rat studies: A systematic review and meta-analysis

Sun

Shi

et al. 2019

Journal of Traditional Chinese Medical Sciences

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Effect of GAPT extract on expression of tau protein and its phosphorylation related enzymes in hippocampal neurons of APPV717I transgenic mice

Abstract: GAPT could attenuate abnormal hyperphosphorylation of tau protein in hippocampal neurons of APPV717I transgenic mice via inhibiting the expression of CDK5 and activating the expression of PP2A.

Cited by 3 publications

References 28 publications

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

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

Adding Chinese herbal medicine to conventional therapy brings cognitive benefits to patients with Alzheimer’s disease: a retrospective analysis

Efficacy of Chinese herbal compound GAPT for the treatment of Alzheimer’s disease during mouse/rat studies: A systematic review and meta-analysis

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