Huatuo Zaizao pill ameliorates cognitive impairment of APP/PS1 transgenic mice by improving synaptic plasticity and reducing Aβ deposition

Zhang, Jinghua; Yu, Liu; Yang, Hui; Zhou, Hui; Su, Jian; Chen, Ling; Zhao, Yang; Wang, Su‐Lei; Liu, Yi; Xu, Yun

doi:10.1186/s12906-018-2237-2

Cited by 15 publications

(9 citation statements)

References 49 publications

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“…It is estimated that AD patients in the world will be more than 150 million by 2050 [ 2 ]. Currently, the drugs used for AD treatment are composed of Donepezil, rivastigmine, galanthamine and memantine [ 5 , 6 ]. But their therapeutic effects are limited.…”

Section: Introductionmentioning

confidence: 99%

Suan-Zao-Ren Decoction ameliorates synaptic plasticity through inhibition of the Aβ deposition and JAK2/STAT3 signaling pathway in AD model of APP/PS1 transgenic mice

Long

et al. 2021

Chin Med

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Background Suan-Zao-Ren Decoction (SZRD) has been widely used to treat neurological illnesses, including dementia, insomnia and depression. However, the mechanisms underlying SZRD’s improvement in cognitive function remain unclear. In this study, we examined SZRD’s effect on APP/PS1 transgenic mice and mechanisms associated with SZRD’s action in alleviating neuroinflammation and improving synaptic plasticity. Methods The APP/PS1 mice were treated with different dosages of SZRD (12.96 and 25.92 g/kg/day, in L-SZRD and H-SZRD groups, respectively) for 4 weeks. Morris water maze was conducted to determine changes in behaviors of the mice after the treatment. Meanwhile, in the samples of the hippocampus, Nissl staining and Golgi-Cox staining were used to detect synaptic plasticity. ELISA was applied to assess the expression levels of Aβ1−40 and Aβ1−42 in the hippocampus of mice. Western blot (WB) was employed to test the protein expression level of Aβ1−42, APP, ADAM10, BACE1, PS1, IDE, IBA1, GFAP, PSD95 and SYN, as well as the expressions of JAK2, STAT3 and their phosphorylation patterns to detect the involvement of JAK2/STAT3 pathway. Besides, we examined the serum and hippocampal contents of IL-1β, IL-6 and TNF-α through ELISA. Results Compared to the APP/PS1 mice without any treatment, SZRD, especially the L-SZRD, significantly ameliorated cognitive impairment of the APP/PS1 mice with decreases in the loss of neurons and Aβ plaque deposition as well as improvement of synaptic plasticity in the hippocampus (P < 0.05 or 0.01). Also, SZRD, in particular, the L-SZRD markedly inhibited the serum and hippocampal concentrations of IL-6, IL-1β and TNF-α, while reducing the expression of p-JAK2-Tyr1007 and p-STAT3-Tyr705 in the hippocampus of the APP/PS1 mice (P < 0.05 or 0.01). Conclusions The SZRD, especially the L-SZRD, may improve the cognitive impairment and ameliorate the neural degeneration in APP/PS1 transgenic mice through inhibiting Aβ accumulation and neuroinflammation via the JAK2/STAT3 pathway.

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Section: Introductionmentioning

confidence: 99%

Suan-Zao-Ren Decoction ameliorates synaptic plasticity through inhibition of the Aβ deposition and JAK2/STAT3 signaling pathway in AD model of APP/PS1 transgenic mice

Long

et al. 2021

Chin Med

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“…All experimental protocols were conducted according to guidelines of the Institutional Animal Care and Use Committee of Institute of Radiation Medicine Chinese Academy of Medical Sciences (Tianjin, China). The mice were randomly divided into five groups (10 mice per group): Wild type group (WT, saline), APP/PS1 mice group (Tg, saline), CG group (2.46 g/kg, based on clinical dosage), Mm group (Mm, 5 mg/kg, according to the Zhang JH et al [ 26 ]), CG combined with Mm group (CG + Mm, 2.46 mg/kg, 5 mg/kg, respectively). All drugs were dissolved in 0.9% physiological saline.…”

Section: Methodsmentioning

confidence: 99%

Cerebralcare Granule® enhances memantine hydrochloride efficacy in APP/PS1 mice by ameliorating amyloid pathology and cognitive functions

Qiao

Zhang

et al. 2021

Chin Med

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Background Alzheimer’s disease (AD) is a progressive neurodegenerative disease characterized by memory deficits and cognitive decline. Current drugs can only relieve symptoms, but cannot really cure AD. Cerebralcare Granule® (CG) is a Traditional Chinese medicine (TCM) containing a variety of biologically active compounds. In our previous studies, CG has shown a beneficial effect against memory impairment in mice caused by d-galactose. However, whether CG can be used as a complementary medicine for the treatment of AD remains unexplored. Here, we use a combination of CG and memantine hydrochloride (Mm) to treat Alzheimer-like pathology and investigate the effects and mechanisms in vivo. Methods The histology of brain was examined with Hematoxylin–eosin (HE) staining, Golgi staining and Thioflavin S staining. ELISA was applied to assess the expression levels or activities of CAT, SOD, GSH-Px, MDA, alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), total bilirubin (TBIL) in serum, as well as the levels of IL-6, IL-1β, and TNF-α in the mice brain. Western blotting was used to assess the expression of β-secretase (BACE1), amyloid precursor protein (APP), APPβ, APPα, synaptophysin (SYN), growth-associated protein 43 (GAP43), and postsynaptic density 95 (PSD95). Results In the present study, the combination group (CG + Mm) significantly attenuated Alzheimer-like behavior without adverse effects in APP/PS1 mice, indicating its high degree of safety and efficacy after long-term treatment. CG + Mm reduced AD pathological biomarker Aβ plaque accumulation by inhibiting BACE1 and APP expression (P < 0.05 or P < 0.001). Besides, the combination group markedly inhibited the levels of IL-1β, IL-6, and TNF-α in hippocampus (P < 0.001), as well as activities of SOD, CAT, and GSH-Px in serum (P < 0.001). By contrast, the combination group improved synaptic plasticity by enhancing SYN, PSD95, and GAP43 expression. Conclusions Taken together, these data supported the notion that CG combined with Mm might ameliorate the cognitive impairment through multiple pathways, suggesting that CG could play a role as complementary medicine to increase anti-AD effect of chemical drugs by reducing Aβ deposition, neuroinflammation, oxidative damage, and improving synaptic plasticity.

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“…The animal experimental procedure was approved by the Animal Care Committee of Jilin University (License No. : 20160518) at 18 May 2016 and conformed to the Animal Ethical Standards and Use Committee at Jilin University [ 63 ].…”

Section: Methodsmentioning

confidence: 99%

“…After mice sacrifice, brains were excised, fixed in 4% paraformaldehyde, and embedded in paraffin. Serial coronal brain sections were cut along the entire rostro-caudal brain axis and stained for IHC analysis using a standard protocol [ 63 ]. After blocking with 5% normal goat serum, the section was incubated with anti-amyloid precursor protein monoclonal antibody (1:500, Abcam, Cambridge, UK), anti-Iba1 monoclonal antibody (1:40, Abcam, Cambridge, UK), and anti-GFAP monoclonal antibody (1:300, CST, Massachusetts, USA) at 4 °C overnight.…”

Section: Methodsmentioning

confidence: 99%

A Novel Peroxidase Mimics and Ameliorates Alzheimer’s Disease-Related Pathology and Cognitive Decline in Mice

Wang

Yuan

et al. 2018

IJMS

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Alzheimer’s disease (AD) is the most common neurodegenerative disorder in the elderly, which is characterized by the accumulation of amyloid β (Aβ) plaques, oxidative stress, and neuronal loss. Therefore, clearing Aβ aggregates and reducing oxidative stress could be an effective therapeutic strategy for AD. Deuterohemin-AlaHisThrValGluLys (DhHP-6), a novel deuterohemin-containing peptide mimetic of the natural microperoxidase-11 (MP-11), shows higher antioxidant activity and stability compared to the natural microperoxidases. DhHP-6 possesses the ability of extending lifespan and alleviating paralysis in the Aβ1-42 transgenic Caenorhabditis elegans CL4176 model of AD, as shown in our previous study. Therefore, this study was aimed at exploring the neuroprotective effect of DhHP-6 in the APPswe/PSEN1dE9 transgenic mouse model of AD. DhHP-6 reduced the diameter and fiber structure of Aβ1-42 aggregation in vitro, as shown by dynamic light scattering and transmission electron microscope. DhHP-6 exerted its neuroprotective effect by inhibiting Aβ aggregation and plaque formation, and by reducing Aβ1-42 oligomers-induced neurotoxicity on HT22 (mouse hippocampal neuronal) and SH-SY5Y (human neuroblastoma) cells. In the AD mouse model, DhHP-6 significantly ameliorated cognitive decline and improved spatial learning ability in behavioral tests including the Morris water maze, Y-maze, novel object recognition, open field, and nest-building test. Moreover, DhHP-6 reduced the deposition of Aβ plaques in the cerebral cortex and hippocampus. More importantly, DhHP-6 restored the morphology of astrocytes and microglia, and significantly reduced the levels of pro-inflammatory cytokines. Our findings provide a basis for considering the non-toxic, peroxidase mimetic DhHP-6 as a new candidate drug against AD.

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Huatuo Zaizao pill ameliorates cognitive impairment of APP/PS1 transgenic mice by improving synaptic plasticity and reducing Aβ deposition

Cited by 15 publications

References 49 publications

Suan-Zao-Ren Decoction ameliorates synaptic plasticity through inhibition of the Aβ deposition and JAK2/STAT3 signaling pathway in AD model of APP/PS1 transgenic mice

Suan-Zao-Ren Decoction ameliorates synaptic plasticity through inhibition of the Aβ deposition and JAK2/STAT3 signaling pathway in AD model of APP/PS1 transgenic mice

Cerebralcare Granule® enhances memantine hydrochloride efficacy in APP/PS1 mice by ameliorating amyloid pathology and cognitive functions

A Novel Peroxidase Mimics and Ameliorates Alzheimer’s Disease-Related Pathology and Cognitive Decline in Mice

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