Dauricine Attenuates Spatial Memory Impairment and Alzheimer-Like Pathologies by Enhancing Mitochondrial Function in a Mouse Model of Alzheimer's Disease

Chen, Chongyang; Liu, Pan; Wang, Jing; Yu, Haitao; Zhang, Zaijun; Li, Jianjun; Chen, Xiao; Zhu, Feiqi; Yang, Xifei

doi:10.3389/fcell.2020.624339

Cited by 18 publications

(8 citation statements)

References 34 publications

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“…In chronic CNS diseases, such as Alzheimer’s disease, dauricine enhances ER-associated degradation by activating X-box binding protein 1, accelerates the degradation of amyloid-beta, has antioxidative and antiapoptotic pharmacological activity in a Caenorhabditis elegans model of Alzheimer’s disease, and enhances mitochondrial function to attenuate spatial memory impairment and Alzheimer’s disease in 3xTg-AD mice. 8 , 9 , 12 , 34 In acute neuronal injury, dauricine alleviates secondary brain injury after intracerebral hemorrhage and inhibits apoptosis and ferroptosis of nerve cells. 10 , 35 However, the pharmacological activity of dauricine in I/R injury and neuroimmunity remains unclear.…”

Section: Discussionmentioning

confidence: 99%

Serpine1 Regulates Peripheral Neutrophil Recruitment and Acts as Potential Target in Ischemic Stroke

Pu¹,

Bao²,

Xia³

et al. 2022

JIR

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Introduction Peripheral neutrophil infiltration can exacerbate ischemia–reperfusion injury. We focused on the relationship between various peripheral immune cells and cerebral ischemia–reperfusion (I/R) injury. Methods In this study, we investigated the effects of dauricine on neuronal injury induced by ischemia–reperfusion and peripheral immune cells after ischemic stroke in mouse model, and we explored the undefined mechanisms of regulating peripheral immune cells through RNA sequencing and various biochemical verification in vitro and in vivo. Results We found that dauricine improved the neurological deficits of I/R injury, reduced the infarct volume, and improved the neurological scores. Furthermore, dauricine reduced the infiltration of neutrophils into the brain after MCAO-R and increased peripheral neutrophils but unchanged the permeability of the endotheliocyte Transwell system in an in vitro blood-brain barrier (BBB) model. RNA sequencing showed that chemotaxis factors, such as CXCL3, CXCL11, CCL20, CCL22, IL12a, IL23a, and serpine1, might play a crucial role. Overexpression of serpine1 reversed LPS-induced migration of neutrophils. Dauricine can directly bind with serpine1 in ligand–receptor docking performed with the Autodock and analyzed with PyMOL. Conclusion We identified chemotaxis factor serpine1 played a crucial role in peripheral neutrophil infiltration, which may contribute to reduce the neuronal injury induced by ischemia–reperfusion. These findings reveal that serpine1 may act as a potential treatment target in the acute stage of ischemic stroke.

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Section: Discussionmentioning

confidence: 99%

Serpine1 Regulates Peripheral Neutrophil Recruitment and Acts as Potential Target in Ischemic Stroke

Pu¹,

Bao²,

Xia³

et al. 2022

JIR

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“…Dauricine alleviated cognitive deficits in 3xTg-AD mice by lowering A β plaques and hyperphosphorylated tau and raising hippocampus ATP levels. After dauricine administration, Aco2, Ndufs1, Cox5a, and SDHB involved in the mitochondrial energy metabolism were significantly increased, while the expression level of synapse-related proteins such as Syn1 and Syn2 were upregulated [ 56 ]. Dauricine regulated the proteins levels of Nrf2 and Kelch-like ECH-associated protein 1 (Keap1) that is necessary for the activation of Nrf2 in APPsw cells [ 57 ].…”

Section: Discussionmentioning

confidence: 99%

Network Pharmacology and Molecular Docking-Based Strategy to Investigate the Multitarget Mechanisms of Shenqi Yizhi Granule on Alzheimer’s Disease

Wang

et al. 2022

Evidence-Based Complementary and Alternative Medicine

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Background. Traditional Chinese herbal medicine draws more attention to explore an effective therapeutic strategy for Alzheimer’s disease (AD). Shenqi Yizhi granule (SQYG), a Chinese herbal recipe, has been applied to ameliorate cognitive impairment in mild-to-moderate AD patients. However, the overall molecular mechanism of SQYG in treating AD has not been clarified. Objective. This study aimed to investigate the molecular mechanism of SQYG on AD using an integration strategy of network pharmacology and molecular docking. Methods. The active compounds of SQYG and common targets between SQYG and AD were screened from databases. The herb-compound network, compound-target network, and protein-protein interaction network were constructed. The enrichment analysis of common targets and molecular docking were performed. Results. 816 compounds and 307 common targets between SQYG and AD were screened. KEGG analysis revealed that common targets were mainly enriched in lipid metabolism, metal ion metabolism, IL-17 signaling pathway, GABA receptor signaling, and neuroactive ligand-receptor interaction. Molecular docking analysis showed high binding affinity between ginsenoside Rg1 and Aβ1–42, tanshinone IIA and BACE1, baicalin, and AchE. Conclusions. The therapeutic mechanisms of SQYG on AD were associated with regulating lipid metabolism, metal ion metabolism, IL-17 signaling pathway, and GABA receptor signaling. Ginsenoside Rg1, tanshinone IIA, baicalin, astragaloside IV, and folic acid may play an important role in AD treatment.

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“…The swim time was set to 60 s. The time spent in searing platform is called escape latency, and swimming trajectories and swimming distance of the mice were recorded within the 60 s period. If the mouse failed to find the platform, alternatively, put the mouse on the platform and stand for another 15 s.The platform was removed on the last day ( Chen et al, 2020 ).…”

Section: Methodsmentioning

confidence: 99%

Chinese Herbal Extracts Exert Neuroprotective Effect in Alzheimer’s Disease Mouse Through the Dopaminergic Synapse/Apoptosis Signaling Pathway

Huang

Zhang

et al. 2022

Front. Pharmacol.

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Background: Alzheimer’s disease (AD) as an age-related, irreversible neurodegenerative disease, characterized by cognitive dysfunction, has become progressively serious with a global rise in life expectancy. As the failure of drug elaboration, considerable research effort has been devoted to developing therapeutic strategies for treating AD. TCM is gaining attention as a potential treatment for AD. Gastrodia elata Blume, Polygala tenuifolia Willd., Cistanche deserticola Ma, Rehmannia lutinosa (Gaertn.)DC., Acorus gramineus Aiton, and Curcuma longa L. (GPCRAC) are all well-known Chinese herbs with neuroprotective benefits and are widely used in traditional Chinese decoction for AD therapy. However, the efficacy and further mechanisms of GPCRAC extracts in AD experimental models are still unclear. The purpose of this study was to investigate the synergistic protective efficacy of GPCRAC extracts (composed of extracts from these six Chinese medicines), and the protein targets mediated by GPCRAC extracts in treating AD.Methods: Scopolamine-induced cognitive impairment mouse model was established to determine the neuroprotective effects of GPCRAC extracts in vivo, as shown by behavioral tests and cerebral cholinergic function assays. To identify the potential molecular mechanism of GPCRAC extracts against AD, label-free quantitative proteomics coupled with tandem mass spectrometry (LC-MS/MS) were performed. The integrated bioinformatics analysis was applied to screen the core differentially expressed proteins in vital canonical pathways. Critical altered proteins were validated by qPCR and Western blotting.Results: Administration of GPCRAC extracts significantly recovered scopolamine-induced cognitive impairment, as evidenced by the improved learning and memory ability, increased Ach content and ChAT activity, as well as decreased AchE activity in the hippocampus of mice. In total, 390 proteins with fold-change>1.2 or <0.83 and p < 0.05 were identified as significant differentially expressed proteins, of which 110 were significantly up-regulated and 25 were significantly down-regulated between control and model group. By mapping the significantly regulated proteins, we identified five hub proteins: PPP2CA, Gsk3β, PP3CC, PRKACA, and BCL-2 that were associated with dopaminergic synapse and apoptosis signaling pathway, respectively. Western blotting and QPCR demonstrate that the expression levels of these core proteins could be significantly improved by the administration of GPCRAC extracts. These pathways and some of the identified proteins are implicated in AD pathogenesis.Conclusion: Administration of GPCRAC extracts was effective on alleviating scopolamine-induced cognitive impairment, which might be through modulation of dopaminergic synapse and apoptosis signaling pathway. Consequently, our quantitative proteome data obtained from scopolamine-treated model mice successfully characterized AD-related biological alterations and proposed novel protein biomarkers for AD.

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Dauricine Attenuates Spatial Memory Impairment and Alzheimer-Like Pathologies by Enhancing Mitochondrial Function in a Mouse Model of Alzheimer's Disease

Cited by 18 publications

References 34 publications

Serpine1 Regulates Peripheral Neutrophil Recruitment and Acts as Potential Target in Ischemic Stroke

Serpine1 Regulates Peripheral Neutrophil Recruitment and Acts as Potential Target in Ischemic Stroke

Network Pharmacology and Molecular Docking-Based Strategy to Investigate the Multitarget Mechanisms of Shenqi Yizhi Granule on Alzheimer’s Disease

Chinese Herbal Extracts Exert Neuroprotective Effect in Alzheimer’s Disease Mouse Through the Dopaminergic Synapse/Apoptosis Signaling Pathway

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