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1.
Food Sci Nutr ; 12(6): 4421-4434, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38873446

RESUMO

With the changes of people's lifestyle, hyperlipidemia and hyperglycemia which were induced from a diet high in both fat and sugar have become serious health concerns. Tree peony seed oil (PSO) is a novel kind of edible oil that shows great potential in the food industry because of its high constituent of unsaturated fatty acids. Based 16S rRNA and gut untargeted metabolomics, this study elucidated that the mechanism of PSO regulating blood glucose (Glu) and lipids. The impact of PSO on gut microbiota balance and gut metabolites of mice with a high-fat diet (HFD) was evaluated. The findings indicated that PSO decreased HFD mice's body weight and fat accumulation, ameliorating the levels of blood lipid, reduced liver fat vacuole levels. What's more PSO modulated the proportion of gut microbiota in HFD mice and enhanced the abundance of probiotics. Furthermore, untargeted metabolomic analysis revealed that PSO not only impacted the generation of short-chain fatty acids (SCFAs) by gut microorganism and altered metabolic pathway but exerted influence on secondary bile acids (BA), amino acid metabolism, and various other metabolites. These results suggested that PSO has the potential function for mitigating HFD-induced hyperlipidemia and hyperglycemia by regulating gut microbiota and host metabolism.

2.
J Pharm Anal ; 14(3): 348-370, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38618251

RESUMO

Emerging research suggests a potential association of progression of Alzheimer's disease (AD) with alterations in synaptic currents and mitochondrial dynamics. However, the specific associations between these pathological changes remain unclear. In this study, we utilized Aß42-induced AD rats and primary neural cells as in vivo and in vitro models. The investigations included behavioural tests, brain magnetic resonance imaging (MRI), liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) analysis, Nissl staining, thioflavin-S staining, enzyme-linked immunosorbent assay, Golgi-Cox staining, transmission electron microscopy (TEM), immunofluorescence staining, proteomics, adenosine triphosphate (ATP) detection, mitochondrial membrane potential (MMP) and reactive oxygen species (ROS) assessment, mitochondrial morphology analysis, electrophysiological studies, Western blotting, and molecular docking. The results revealed changes in synaptic currents, mitophagy, and mitochondrial dynamics in the AD models. Remarkably, intervention with Dengzhan Shengmai (DZSM) capsules emerged as a pivotal element in this investigation. Aß42-induced synaptic dysfunction was significantly mitigated by DZSM intervention, which notably amplified the frequency and amplitude of synaptic transmission. The cognitive impairment observed in AD rats was ameliorated and accompanied by robust protection against structural damage in key brain regions, including the hippocampal CA3, primary cingular cortex, prelimbic system, and dysgranular insular cortex. DZSM intervention led to increased IDE levels, augmented long-term potential (LTP) amplitude, and enhanced dendritic spine density and length. Moreover, DZSM intervention led to favourable changes in mitochondrial parameters, including ROS expression, MMP and ATP contents, and mitochondrial morphology. In conclusion, our findings delved into the realm of altered synaptic currents, mitophagy, and mitochondrial dynamics in AD, concurrently highlighting the therapeutic potential of DZSM intervention.

3.
Front Chem ; 12: 1356458, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38496269

RESUMO

Background: With the increasing global prevalence of hypertension, a condition that can severely affect multiple organs, there is a growing need for effective treatment options. Uncaria rhynchophylla-Alisma plantago-aquatica L. (UR-AP) is a traditional drug pair used for treating hypertension based on the liver-kidney synergy concept. However, the detailed molecular mechanisms underlying its efficacy remain unclear. Methods: This study utilized an integrative approach combining network pharmacology, cluster analysis, and molecular docking to uncover the bioactive components and targets of UR-AP in the treatment of hypertension. Initially, we extracted data from public databases to identify these components and targets. A Protein-Protein Interaction (PPI) network was constructed, followed by enrichment analysis to pinpoint the bioactive components, core targets, and pivotal pathways. Cluster analysis helped in identifying key sub-networks and hypothesizing primary targets. Furthermore, molecular docking was conducted to validate the interaction between the core targets and major bioactive components, thus confirming their potential efficacy in hypertension treatment. Results: Network pharmacological analysis identified 58 bioactive compounds in UR-AP, notably quercetin, kaempferol, beta-sitosterol (from Uncaria rhynchophylla), and Alisol B, alisol B 23-acetate (from Alisma plantago-aquatica L.), as pivotal bioactives. We pinpointed 143 targets common to both UR-AP and hypertension, highlighting MAPK1, IL6, AKT1, VEGFA, EGFR, and TP53 as central targets involved in key pathways like diastolic and endothelial function, anti-atherosclerosis, AGE-RAGE signaling, and calcium signaling. Cluster analysis emphasized IL6, TNF, AKT1, and VEGFA's roles in atherosclerosis and inflammation. Molecular docking confirmed strong interactions between these targets and UR-AP's main bioactives, underscoring their therapeutic potential. Conclusion: This research delineates UR-AP's pharmacological profile in hypertension treatment, linking traditional medicine with modern pharmacology. It highlights key bioactive components and their interactions with principal targets, suggesting UR-AP's potential as a novel therapeutic option for hypertension. The evidence from molecular docking studies supports these interactions, indicating the relevance of these components in affecting hypertension pathways. However, the study acknowledges its limitations, including the reliance on in silico analyses and the need for in vivo validation. These findings pave the way for future clinical research, aiming to integrate traditional medicine insights with contemporary scientific approaches for developing innovative hypertension therapies.

4.
Eur J Med Res ; 29(1): 199, 2024 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-38528586

RESUMO

BACKGROUND: Lipid metabolism changes occur in early Alzheimer's disease (AD) patients. Yet little is known about metabolic gene changes in early AD cortex. METHODS: The lipid metabolic genes selected from two datasets (GSE39420 and GSE118553) were analyzed with enrichment analysis. Protein-protein interaction network construction and correlation analyses were used to screen core genes. Literature analysis and molecular docking were applied to explore potential therapeutic drugs. RESULTS: 60 lipid metabolic genes differentially expressed in early AD patients' cortex were screened. Bioinformatics analyses revealed that up-regulated genes were mainly focused on mitochondrial fatty acid oxidation and mediating the activation of long-chain fatty acids, phosphoproteins, and cholesterol metabolism. Down-regulated genes were mainly focused on lipid transport, carboxylic acid metabolic process, and neuron apoptotic process. Literature reviews and molecular docking results indicated that ACSL1, ACSBG2, ACAA2, FABP3, ALDH5A1, and FFAR4 were core targets for lipid metabolism disorder and had a high binding affinity with compounds including adenosine phosphate, oxidized Photinus luciferin, BMS-488043, and candidate therapeutic drugs especially bisphenol A, benzo(a)pyrene, ethinyl estradiol. CONCLUSIONS: AD cortical lipid metabolism disorder was associated with the dysregulation of the PPAR signaling pathway, glycerophospholipid metabolism, adipocytokine signaling pathway, fatty acid biosynthesis, fatty acid degradation, ferroptosis, biosynthesis of unsaturated fatty acids, and fatty acid elongation. Candidate drugs including bisphenol A, benzo(a)pyrene, ethinyl estradiol, and active compounds including adenosine phosphate, oxidized Photinus luciferin, and BMS-488043 have potential therapeutic effects on cortical lipid metabolism disorder of early AD.


Assuntos
Doença de Alzheimer , Compostos Benzidrílicos , Indóis , Transtornos do Metabolismo dos Lipídeos , Fenóis , Piperazinas , Ácido Pirúvico , Humanos , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/genética , Doença de Alzheimer/metabolismo , Simulação de Acoplamento Molecular , Benzo(a)pireno , Ácidos Graxos/metabolismo , Redes e Vias Metabólicas , Etinilestradiol , Nucleotídeos de Adenina/metabolismo , Luciferinas
5.
Plants (Basel) ; 12(17)2023 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-37687358

RESUMO

Tree peony is a unique oil plant resource in China, and tree peony seed oil is one of the healthy edible oils with a very promising future. However, the main oil tree peony cultivars promoted in China are Paeonia ostii 'Fengdan' and Paeonia rockii. In order to explore new oil tree peony cultivars, 68 tree peony cultivars were investigated and cultivars with oil potential were selected by cluster analysis and grey relational analysis (GRA) in this study. The results demonstrated that the 68 cultivars varied significantly in terms of agronomic characteristics (p < 0.05), with the coefficient of variation in seed yield per plant reaching a high of 75.36%. The oil content of 46 cultivars was higher than 'Fengdan' (20.87 ± 0.26%) and 'Zibanbai' (21.24 ± 1.01%), while the alpha-linolenic acids and total unsaturated fatty acid contents of 26 cultivars were higher than 'Fengdan' (39.79 ± 1.13% and 88.99 ± 0.47%) and 'Zibanbai' (40.51 ± 0.09% and 93.59 ± 0.09%). Finally, three cultivars with better integrated traits were selected by cluster analysis and grey relational analysis (GRA), comprising of 'Changshoule', 'Xianchizhenghui', and 'Yupantuojin'. The contents of alpha-linolenic acids and total unsaturated fatty acids in 'Changshoule' (47.98 ± 0.17% and 93.60 ± 0.08%), 'Xianchizhenghui' (49.44 ± 0.63% and 93.80 ± 0.06%), and 'Yupantuojin' (40.46 ± 0.26% and 93.58 ± 0.06%) were higher than that of 'Fengdan' (39.79 ± 1.13% and 88.99 ± 0.47%). In general, these cultivars can be used as hybrid parental materials for breeding new excellent oil tree peony cultivars.

6.
Eur J Nutr ; 62(7): 2991-3007, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37460822

RESUMO

PURPOSE: Prebiotics, including fructo-oligosaccharides (FOS) and galacto-oligosaccharides (GOS), stimulate beneficial gut bacteria and may be helpful for patients with Alzheimer's disease (AD). This study aimed to compare the effects of FOS and GOS, alone or in combination, on AD mice and to identify their underlying mechanisms. METHODS: Six-month-old APP/PS1 mice and wild-type mice were orally administered FOS, GOS, FOS + GOS or water by gavage for 6 weeks and then subjected to relative assays, including behavioral tests, biochemical assays and 16S rRNA sequencing. RESULTS: Through behavioral tests, we found that GOS had the best effect on reversing cognitive impairment in APP/PS1 mice, followed by FOS + GOS, while FOS had no effect. Through biochemical techniques, we found that GOS and FOS + GOS had effects on multiple targets, including diminishing Aß burden and proinflammatory IL-1ß and IL-6 levels, and changing the concentrations of neurotransmitters GABA and 5-HT in the brain. In contrast, FOS had only a slight anti-inflammatory effect. Moreover, through 16S rRNA sequencing, we found that prebiotics changed composition of gut microbiota. Notably, GOS increased relative abundance of Lactobacillus, FOS increased that of Bifidobacterium, and FOS + GOS increased that of both. Furthermore, prebiotics downregulated the expression levels of proteins of the TLR4-Myd88-NF-κB pathway in the colons and cortexes, suggesting the involvement of gut-brain mechanism in alleviating neuroinflammation. CONCLUSION: Among the three prebiotics, GOS was the optimal one to alleviate cognitive impairment in APP/PS1 mice and the mechanism was attributed to its multi-target role in alleviating Aß pathology and neuroinflammation, changing neurotransmitter concentrations, and modulating gut microbiota.


Assuntos
Doença de Alzheimer , Disfunção Cognitiva , Camundongos , Animais , Eixo Encéfalo-Intestino , Prebióticos , RNA Ribossômico 16S/genética , Doenças Neuroinflamatórias , Disfunção Cognitiva/terapia , Doença de Alzheimer/terapia , Oligossacarídeos/farmacologia
7.
Adv Exp Med Biol ; 1419: 111-126, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37418210

RESUMO

Characterized by the gradual loss of physiological integrity, impaired function, and increased susceptibility to death, aging is considered the primary risk factor for major human diseases, such as cancer, diabetes, cardiovascular disorders, and neurodegenerative diseases. The time-dependent accumulation of cellular damage is widely considered the general cause of aging. While the mechanism of normal aging is still unresolved, researchers have identified different markers of aging, including genomic instability, telomere attrition, epigenetic alterations, loss of proteostasis, deregulated nutrient-sensing, mitochondrial dysfunction, cellular senescence, stem cell exhaustion, and altered intercellular communication. Theories of aging can be divided into two categories: (1) aging is a genetically programmed process, and (2) aging is a random process caused by gradual damage to the organism over time as a result of its vital activities. Aging affects the entire human body, and aging of the brain is undoubtedly different from all other organs, as neurons are highly differentiated postmitotic cells, and the lifespan of most neurons in the postnatal period is equal to the lifespan of the brain. In this chapter, we discuss the conserved mechanisms of aging that may underlie the changes observed in the aging brain, with a focus on mitochondrial function and oxidative stress, autophagy and protein turnover, insulin/IGF signaling, target of rapamycin (TOR) signaling, and sirtuin function.


Assuntos
Envelhecimento , Senescência Celular , Humanos , Envelhecimento/metabolismo , Diferenciação Celular , Transdução de Sinais , Encéfalo/metabolismo
8.
Aging (Albany NY) ; 15(10): 4334-4362, 2023 05 20.
Artigo em Inglês | MEDLINE | ID: mdl-37211381

RESUMO

Exploration and utilization of exosome biomarkers and their related functions provide the possibility for the diagnosis and treatment of post-stroke cognitive impairment (PSCI). To identify the new diagnostic and prognostic biomarkers of plasma exosome were uzed label-free quantitative proteomics and biological information analysis in PSCI patients. Behavioral assessments were performed, including the Mini-Mental Status Examination (MMSE), the Montreal Cognitive Assessment (MoCA), the Barthel index, the Morse Fall Seale (MFS) between control group (n = 10) and PSCI group (n = 10). The blood samples were collected to analyse the biomarker and differentially expressed proteins of plasma exosome using label-free quantitative proteomics and biological information. The exosomes marker proteins were determined by Western blot. The exosome morphology was observed by transmission electron microscopy. The scores of MMSE and MoCA were significantly decreased in the PSCI group. The PT% and high-density lipoprotein decreased and the INR ratio increased in PSCI group. The mean size of exosome was approximately 71.6 nm and the concentration was approximately 6.8E+7 particles/mL. Exosome proteomics identified 259 differentially expressed proteins. The mechanisms of cognitive impairment are related to regulate the degradation of ubiquitinated proteins, calcium dependent protein binding, cell adhesive protein binding, formation of fibrin clot, lipid metabolism and ATP-dependent degradation of ubiquitinated proteins in plasma exosome of PSCI patients. Plasma levels of YWHAZ and BAIAP2 were significantly increased while that of IGHD, ABCB6 and HSPD1 were significantly decreased in PSCI patients. These proteins might be target-related proteins and provide global insights into pathogenesis mechanisms of PSCI at plasma exosome proteins level.


Assuntos
Disfunção Cognitiva , Exossomos , Acidente Vascular Cerebral , Humanos , Proteínas Ubiquitinadas , Proteômica , Disfunção Cognitiva/psicologia , Biomarcadores
9.
Phytomedicine ; 114: 154762, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-36965372

RESUMO

BACKGROUND: Alzheimer's disease (AD) is a neurogenerative disease and remains no effective method for stopping its progress. Ferroptosis and adaptive immunity have been proven to contribute to AD pathogenesis. Salidroside exhibits neuroprotective and immunomodulatory effects. However, the underlying mechanisms linking salidroside, ferroptosis, and adaptive immunity in AD remain uncertain. PURPOSE: The objective of this study is to explore the neuroprotective effects and the potential molecular mechanisms of salidroside against neuronal ferroptosis and CD8+ T cell infiltration in senescence-accelerated mouse prone 8 (SAMP8) mice. STUDY DESIGN AND METHODS: SAMP8 mice were employed as an AD model and were treated with salidroside for 12 weeks. Behavioral tests, immunohistochemistry, HE and Nissl staining, immunofluorescence, transmission electron microscopy, quantitative proteomics, bioinformatic analysis, flow cytometry, iron staining, western blotting, and molecular docking were performed. RESULTS: Treatment with salidroside dose-dependently attenuated cognitive impairment, reduced the accumulation of Aß plaques and restored neuronal damage. Salidroside also suppressed the infiltration of CD8+T cells, oxidative stress, and inflammatory cytokines, and improved mitochondrial metabolism, iron metabolism, lipid metabolism, and redox in the SAMP8 mice brain. The administration of salidroside decreased iron deposition, reduced TFR1, and ACSL4 protein expression, upregulated SLC7A11, and GPX4 protein expression, and promoted the Nrf2/GPX4 axis activation. CONCLUSION: In conclusion, neuronal ferroptosis and CD8+T cells are involved in the process of cognitive impairment in SAMP8 mice. Salidroside alleviates cognitive impairment and inhibits neuronal ferroptosis. The underlying mechanisms may involve the Nrf2/GPX4 axis activation and reduction in CD8+T cells infiltration. This study provides some evidence for the roles of salidroside in adaptive immunity and neuronal ferroptosis in SAMP8 mice.


Assuntos
Doença de Alzheimer , Disfunção Cognitiva , Ferroptose , Animais , Camundongos , Doença de Alzheimer/metabolismo , Disfunção Cognitiva/metabolismo , Ferro , Simulação de Acoplamento Molecular , Fator 2 Relacionado a NF-E2/metabolismo
10.
Cereb Cortex ; 33(6): 2901-2911, 2023 03 10.
Artigo em Inglês | MEDLINE | ID: mdl-35909217

RESUMO

BACKGROUND: Understanding the characteristics of intrinsic connectivity networks (ICNs) in terms of both glucose metabolism and functional connectivity (FC) is important for revealing cognitive aging and neurodegeneration, but the relationships between these two aspects during aging has not been well established in older adults. OBJECTIVE: This study is to assess the relationship between age-related glucose metabolism and FC in key ICNs, and their direct or indirect effects on cognitive deficits in older adults. METHODS: We estimated the individual-level standard uptake value ratio (SUVr) and FC of eleven ICNs in 59 cognitively unimpaired older adults, then analyzed the associations of SUVr and FC of each ICN and their relationships with cognitive performance. RESULTS: The results showed both the SUVr and FC in the posterior default mode network (pDMN) had a significant decline with age, and the association between them was also significant. Moreover, both decline of metabolism and FC in the pDMN were significantly correlated with executive function decline. Finally, mediation analysis revealed the glucose metabolism mediated the FC decline with age and FC mediated the executive function deficits. CONCLUSIONS: Our findings indicated that covariance between glucose metabolism and FC in the pDMN is one of the main routes that contributes to age-related executive function decline.


Assuntos
Transtornos Cognitivos , Função Executiva , Humanos , Idoso , Encéfalo/diagnóstico por imagem , Envelhecimento/psicologia , Glucose , Imageamento por Ressonância Magnética/métodos , Mapeamento Encefálico
11.
Artigo em Inglês | MEDLINE | ID: mdl-36248435

RESUMO

Background: Sjögren's syndrome (SS) is a chronic autoimmune disease characterized by progressive oral and ocular dryness that correlates poorly with autoimmune damage to the glands. CheReCunJin (CRCJ) formula is a prescription formulated according to the Chinese medicine theory for SS treatment. Objective: This study aimed to explore the underlying mechanisms of CRCJ against SS. Methods: The databases, including Traditional Chinese Medicine System Pharmacology, Encyclopedia of Traditional Chinese Medicine, Bioinformatics Analysis Tool for the molecular mechanism of Traditional Chinese Medicine, and Traditional Chinese Medicine Integrated Databases, obtained the active ingredients and predicted targets of CRCJ. Then, DrugBank, Therapeutic Target Database, Genecards, Comparative Toxicogenomics Database, and DisGeNET disease databases were used to screen the predicted targets of SS. Intersected targets of CRCJ and SS were visualized by using Venn diagrams. The overlapping targets were uploaded to the protein-protein interaction network analysis search tool. Cytoscape 3.8.2 software constructed a "compound-targets-disease" network. Gene Ontology and the Kyoto Encyclopedia of Genes and Genomes analyses characterized potential targets' biological functions and pathways. AutoDock Vina 1.1.2 software was used to research and verify chemical effective drug components and critical targets. Results: From the database, we identified 878 active components and 2578 targets of CRCJ, and 827 SS-related targets. 246 SS-related genes in CRCJ were identified by intersection analysis, and then ten hub genes were identified as crucial potential targets from PPI, including ALB, IL-6, TNF, INS, AKT1, IL1B, VEGFA, TP53, JUN, and TLR4. The process of CRCJ action against SS was mainly involved in human cytomegalovirus infection and Th17 cell differentiation, as well as the toll-like receptor signaling and p53 signaling pathways. Molecular docking showed that the bioactive compounds of CRCJ had a good binding affinity with hub targets. Conclusions: The results showed that CRCJ could activate multiple pathways and treat SS through multiple compounds and targets. This study lays a foundation for better elucidation of the molecular mechanism of CRCJ in the treatment of SS, and also provides basic guidance for future research on Chinese herbal compounds.

12.
J Alzheimers Dis ; 89(3): 955-975, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35964195

RESUMO

BACKGROUND: Scutellarin, a flavonoid purified from the Chinese herb Erigeron breviscapus, has been reported to prevent Alzheimer's disease (AD) by affecting Aß assembly. Given the low brain uptake rate of scutellarin, we hypothesize that the microbiota-gut-brain axis may be a potential route by which scutellarin prevents AD. OBJECTIVE: This study aimed to explore the microbiota-gut-brain mechanism by which scutellarin prevented AD. METHODS: Scutellarin was administrated to APP/PS1 mouse model of AD for two months, and the behaviors, pathological changes as well as gut microbial changes in APP/PS1 mice were evaluated after scutellarin treatment. RESULTS: This study found that scutellarin improved Aß pathology, neuroinflammation, and cognitive deficits in APP/PS1 mice. It elucidated the effects of scutellarin on the diversity and activity of gut microbiota in APP/PS1 mice and these findings promoted us to focus on inflammation-related bacteria and short-chain fatty acids (SCFAs). Cognitive behaviors were significantly associated with inflammatory cytokines and inflammation-related bacteria, suggesting that microbiota-gut-brain axis was involved in this model and that inflammatory pathway played a crucial role in this axis. Moreover, we observed that cAMP-PKA-CREB-HDAC3 pathway downstream of SCFAs was activated in microglia of AD and inactivated by scutellarin. Furthermore, by chromatin immunoprecipitation (ChIP) assays, we found that the increased association between acetylated histone 3 and interleukin-1ß (IL-1ß) promoter in AD mice was reversed by scutellarin, leading to a decreased level of IL-1ß in scutellarin-treated AD mice. CONCLUSION: Scutellarin reverses neuroinflammation and cognitive impairment in APP/PS1 mice via beneficial regulation of gut microbiota and cAMP-PKA-CREB-HDAC3 signaling in microglia.


Assuntos
Doença de Alzheimer , Disfunção Cognitiva , Microbioma Gastrointestinal , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/genética , Doença de Alzheimer/metabolismo , Peptídeos beta-Amiloides/metabolismo , Precursor de Proteína beta-Amiloide/genética , Precursor de Proteína beta-Amiloide/metabolismo , Animais , Apigenina/farmacologia , Apigenina/uso terapêutico , Eixo Encéfalo-Intestino , Disfunção Cognitiva/complicações , Disfunção Cognitiva/tratamento farmacológico , Modelos Animais de Doenças , Glucuronatos , Histonas , Inflamação/complicações , Interleucina-1beta/metabolismo , Camundongos , Camundongos Transgênicos , Presenilina-1/metabolismo
13.
Artigo em Inglês | MEDLINE | ID: mdl-35795284

RESUMO

Background: Beta-amyloid (Aß) peptide is a widely recognized pathological marker of Alzheimer's disease (AD). Salidroside and Hedysari Radix polysaccharide (HRP) were extracted from Chinese herb medicine Rhodiola rosea L and Hedysarum polybotrys Hand-Mazz, respectively. The neuroprotective effects and mechanisms of the combination of salidroside and Hedysari Radix polysaccharide (CSH) against Aß 25-35 induced neurotoxicity remain unclear. Objective: This study aims to investigate the neuroprotective effects and pharmacological mechanisms of CSH on Aß 25-35-induced HT22 cells. Materials and Methods: HT22 cells were pretreated with various concentrations of salidroside or HRP for 24 h, followed by exposed to 20 µm Aß 25-35 in the presence of salidroside or RHP for another 24 h. In a CSH protective assay, HT22 cells were pretreated with 40 µm salidroside and 20 µg/mL HRP for 24 h. The cell viability assay, cell morphology observation, determination of mitochondrial membrane potential (MMP), reactive oxygen species (ROS), and cell apoptosis rate were performed. The mRNA expression of protein kinase C-beta (PKCß), Bax, and Bcl-2 were measured by qRT-PCR. The protein expression levels of cleaved caspase-3, Cyt-C, PKCß, phospho-ERK1/2, Bax, and Bcl-2 were measured by Western blot. Results: CSH treatment increased cell viability, MMP, and decreased ROS generation in Aß 25-35-induced HT22 cells. PKCß and Bcl-2 mRNA expression were elevated by CSH while Bax was decreased. CSH increased the protein expression levels of PKCß, Bcl-2, and phospho-ERK1/2, and decreased those of Bax, Cyt-C, and cleaved caspase-3. Conclusions: CSH treatment have protective effects against Aß 25-35-induced cytotoxicity through decreasing ROS levels, increasing MMP, inhibiting early apoptosis, and regulating PKC/ERK pathway in HT22 cells. CSH may be a potential therapeutic agent for treating or preventing neurodegenerative diseases.

14.
Artigo em Inglês | MEDLINE | ID: mdl-35535155

RESUMO

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 Aß 1-42, 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.

15.
Radiol Artif Intell ; 3(5): e200171, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34617021

RESUMO

PURPOSE: To determine whether a brain age prediction model could quantify individual deviations from a healthy brain-aging trajectory (predicted age difference [PAD]) in patients with amnestic mild cognitive impairment (aMCI) and to determine if PAD was associated with individual cognitive impairment. MATERIALS AND METHODS: In this retrospective study, a machine learning approach was trained to determine brain age based on T1-weighted MRI scans. Two datasets were used for model training and testing-the Beijing Aging Brain Rejuvenation Initiative (BABRI) (616 healthy controls and 80 patients with aMCI, 2010-2018) and the Alzheimer's Disease Neuroimaging Initiative (ADNI) (589 healthy controls and 144 patients with aMCI, 2010-2018). A total of 974 healthy controls were used for model training (490 from BABRI and 484 from ADNI; age range, 49-95 years). The trained model was then tested on both healthy controls (126 from BABRI and 105 from ADNI) and patients with aMCI (80 from BABRI and 144 from ADNI) to estimate PAD (predicted age - actual age). Furthermore, the associations between PAD with cognitive impairment, genetic risk factors and pathologic markers of Alzheimer disease (AD), and clinical progression in patients with aMCI were examined using a partial correlation analysis, a two-way analysis of covariance, and a general linear model, respectively. RESULTS: Based on the prediction model, patients with aMCI were found to have higher PADs than those of healthy controls (BABRI: 2.65 ± 4.91 [standard deviation] vs 0.18 ± 4.79 [P < .001]; ADNI: 1.68 ± 5.28 vs 0.05 ± 4.41 [P < .001]). Moreover, the PAD was significantly associated with individual cognitive impairment in several cognitive domains in patients with aMCI (P < .05, corrected). When considering different AD-related risk factors, apolipoprotein E ε4 allele carriers were observed to have higher PADs than noncarriers (3.76 ± 4.82 vs 0.10 ± 5.05; P = .017), and patients with amyloid-positive aMCI were observed to have higher PADs than patients with amyloid-negative status (2.40 ± 5.25 vs 0.93 ± 5.20; P = .003). Finally, PAD combined with other markers of AD at baseline for differentiating between progressive and stable aMCI resulted in an area under the curve value of 0.87. CONCLUSION: The PAD is a sensitive imaging marker related to individual cognitive differences in patients with aMCI.Keywords: MR Imaging, Brain/Brain Stem, Brain Age, Machine Learning, Mild Cognitive Impairment, Structural MRI Supplemental material is available for this article. © RSNA, 2021.

16.
Front Pharmacol ; 12: 712436, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34526899

RESUMO

Acute ischemic stroke (AIS) is a global health burden and cognitive impairment is one of its most serious complication. Adequate interventions for AIS may have the potential to improve cognitive outcomes. In the present study, we selected Erigeron breviscapus (Vaniot) Hand.-Mazz. injection (Dengzhanxixin injection, DZXI), a widely used Chinese herbal injection, in contrast to edaravone as the positive control drug to test its potential to ameliorates neurological and cognitive impairments caused by AIS. We performed a 2-week randomized trial with these two drugs in AIS patients presenting mild to moderate cognitive impairments. Neuropsychological tests and MRI examinations showed that DZXI attenuated the neurological and cognitive impairments of patients and protected the grey matter in specific regions from ischemic damage. Notably, DZXI exerted better effects than edaravone in some neuropsychological tests, probably due to the protective effect of DZXI on grey matter. To explore the therapeutic mechanisms, we carried out an experiment with a middle cerebral artery occlusion rat model. We found that DZXI decreased the infarct volume and increased the survival of neuronal cells in the ischemic penumbra; furthermore, DZXI modulated the mitochondrial respiratory chain process and preserved the mitochondrial structure in the brain tissue. Overall, our data suggested that the administration of DZXI is effective at ameliorating neurological and cognitive impairments in AIS, and the underlying mechanisms are related to the protective effects of DZXI on cerebral neurons and neuronal mitochondria.

17.
Alzheimers Dement ; 17(10): 1610-1618, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-33792187

RESUMO

Facing considerable challenges associated with aging and dementia, China urgently needs an evidence-based health-care system for prevention and management of dementia. The Beijing Aging Brain Rejuvenation Initiative (BABRI) is a community-based cohort study initiated in 2008 that focuses on asymptomatic stages of dementia, aims to develop community-based prevention strategies for cognitive impairment, and provides a platform for scientific research and clinical trials. Thus far, BABRI has recruited 10,255 participants (aged 50 and over, 60.3% female), 2021 of whom have been followed up at least once at a 2- or 3-year interval. This article presents aims and study design of BABRI; summarizes preliminary behavioral and neuroimaging findings on mild cognitive impairment (MCI) and results of clinical trials on MCI; and discusses issues concerning early prevention in community, MCI diagnosis methods, and applications of database of aging and dementia. BABRI is proposed to build a systematic framework on brain health in old age.


Assuntos
Envelhecimento/fisiologia , Doença de Alzheimer/diagnóstico , Disfunção Cognitiva , Progressão da Doença , Idoso , Pequim , China , Disfunção Cognitiva/diagnóstico por imagem , Disfunção Cognitiva/prevenção & controle , Estudos de Coortes , Estudos Transversais , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Neuroimagem
18.
J Am Med Dir Assoc ; 22(7): 1500-1506.e3, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33493465

RESUMO

OBJECTIVES: To address the condition that community-based geriatric services for the assessment and promotion of older adults' cognitive ability systemically aimed at delaying or preventing dementia is lacking in China. DESIGN: A community-based model including cognitive assessment and training, geriatric health guidance and long-term support was designed based on a prospective cohort study. SETTING AND PARTICIPANTS: Participants (N = 5593) were all from an ongoing cohort study, the Beijing Aging Brain Rejuvenation Initiative (BABRI) study. METHODS: We conducted receiver operating characteristic, stepwise logistic regression and branch-and-bound algorithm analyses to select the most effective tests from the BABRI neuropsychological test battery. Canonical discriminant analysis was conducted to extract the first canonical variable as a composite index of the tests. In addition, we developed comprehensive surveys and computerized cognitive trainings targeting every cognitive domain. RESULTS: The BABRI brain health system (BABRI-BHS) was designed to include SCREEN, ASSESS, and DIAGNOSE sessions. When distinguishing cognitively impaired older adults from cognitively healthy older adults, the canonical variable extracted from tests in the SCREEN session achieved an area under the curve (AUC) of 0.730 [95% confidence interval (95% CI) 0.671-0.789], with a sensitivity of 0.630 and a specificity of 0.780; in the ASSESS session, the AUC was 0.906 (95% CI 0.894-0.917), the sensitivity was 0.809, and the specificity was 0.854. A stepwise screening pathway is recommended when using the BABRI-BHS in communities to divide older adults into subtypes and to provide targeted interventions and long-term geriatric health guidance. CONCLUSIONS AND IMPLICATIONS: The BABRI-BHS is an effective and efficient geriatric health care solution that is suitable for community-based dementia risk screening, providing stepwise cognitive assessments and helping older adults acquire tailored interventions and guidance conveniently.


Assuntos
Demência , Rejuvenescimento , Idoso , Envelhecimento , Pequim , Encéfalo , China , Estudos de Coortes , Demência/diagnóstico , Avaliação Geriátrica , Humanos , Testes Neuropsicológicos , Estudos Prospectivos
19.
Neuroimage ; 226: 117591, 2021 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-33248254

RESUMO

Normal aging is accompanied by structural degeneration and glucose hypometabolism in the human brain. However, the relationship between structural network disconnections and hypometabolism in normal aging remains largely unknown. In the present study, by combining MRI and PET techniques, we investigated the metabolic mechanism of the structural brain connectome and its relationship with normal aging in a cross-sectional, community-based cohort of 42 cognitively normal elderly individuals aged 57-84 years. The structural connectome was constructed based on diffusion MRI tractography, and the network efficiency metrics were quantified using graph theory analyses. FDG-PET scanning was performed to evaluate the glucose metabolic level in the cortical regions of the individuals. The results of this study demonstrated that both network efficiency and cortical metabolism decrease with age (both p < 0.05). In the subregions of the bilateral thalamus, significant correlations between nodal efficiency and cortical metabolism could be observed across subjects. Individual-level analyses indicated that brain regions with higher nodal efficiency tend to exhibit higher metabolic levels, implying a tight coupling between nodal efficiency and glucose metabolism (r = 0.56, p = 1.15 × 10-21). Moreover, efficiency-metabolism coupling coefficient significantly increased with age (r = 0.44, p = 0.0046). Finally, the main findings were also reproducible in the ADNI dataset. Together, our results demonstrate a close coupling between structural brain connectivity and cortical metabolism in normal elderly individuals and provide new insight that improve the present understanding of the metabolic mechanisms of structural brain disconnections in normal aging.


Assuntos
Envelhecimento/fisiologia , Encéfalo/fisiologia , Glucose/metabolismo , Rede Nervosa/fisiologia , Idoso , Idoso de 80 Anos ou mais , Conectoma/métodos , Imagem de Tensor de Difusão/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Tomografia por Emissão de Pósitrons/métodos
20.
J Tradit Chin Med ; 40(6): 891-896, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33258339

RESUMO

OBJECTIVE: To summarize the evidence from Traditional Chinese Medicine (TCM) practice in the treatment of coronavirus disease 2019 (COVID-19) and provide timely clinical practice guidance. METHODS: The guidelines were developed in accordance with the World Health Organization rapid guideline process. The evidence on TCM for COVID-19 from published guidelines, direct and indirect published clinical evidence, first hand clinical data, and expert experience and consensus were collected. The grading of recommendations assessment, development and evaluation (GRADE) method was used to grade the evidence and make the recommendations. RESULTS: Based on the available evidence, the guidelines recommended 17 Chinese medicines for COVID-19: 2 Chinese herbal granules, 7 Chinese patent medicines, and 8 Chinese herbal injections. CONCLUSION: As the literature search was conducted on March, any subsequent versions of these guidelines require an up-to-date literature review. We hope that the evidence summary in these will be helpful in global efforts to address COVID-19.


Assuntos
Medicamentos de Ervas Chinesas/uso terapêutico , Medicina Tradicional Chinesa/métodos , Humanos , SARS-CoV-2/patogenicidade , Tratamento Farmacológico da COVID-19
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