Brain Research最新文献

{"title":"Parkinson’s disease and brain insulin signaling: Mechanisms and potential role of GLP-1 mimetics","authors":"Behina Foroozanmehr ,&nbsp;Mohammad Amin Hemmati ,&nbsp;Habib Yaribeygi ,&nbsp;Sercan Karav ,&nbsp;Tannaz Jamialahmadi ,&nbsp;Amirhossein Sahebkar","doi":"10.1016/j.brainres.2025.149738","DOIUrl":"10.1016/j.brainres.2025.149738","url":null,"abstract":"<div><div>Parkinson’s disease (PD) is a common neurodegenerative disorder characterized primarily by the degeneration of dopaminergic neurons in the <em>substantia nigra pars compacta</em>. The pathophysiology of PD is complex and multifactorial involving genetic factors, oxidative stress, mitochondrial dysfunction, impaired protein clearance, and neuroinflammation but recent evidence emphasizes the role of impaired brain insulin signaling. Insulin is a metabolic hormone with extensive effects on metabolic substrates but recent studies have demonstrated that it is also involved in central signaling pathways and induces different brain areas related to food craving, motor activities, cognitive abilities, and emotional feelings. Hence, it has been suggested that induction of brain insulin sensitivity may be a promising treatment for PD. Glucagon-like peptide-1 (GLP-1) mimetics are a new-generation class of antidiabetics that normalize glucose homeostasis <em>via</em> several pathways. Recent studies suggest extra-glycemic benefits for GLP-1 mimetics against PD. GLP-1 mimetics can prevent or slow PD progression. Additionally, these agents can improve cognitive functions <em>by</em> improving brain insulin signaling pathways. In this review, we aim to highlight the role of brain insulin signaling in PD pathophysiology and discuss the possible benefits of GLP-1 mimetics in PD management.</div></div>","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":"1862 ","pages":"Article 149738"},"PeriodicalIF":2.7,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144190211","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The effect of epilepsy on anxiety, depression, as well as prognostic value among adult low-grade gliomas patients","authors":"Kun Zhao,&nbsp;Jiayu Gu,&nbsp;Beichuan Zhao","doi":"10.1016/j.brainres.2025.149737","DOIUrl":"10.1016/j.brainres.2025.149737","url":null,"abstract":"<div><h3>Background</h3><div>Epilepsy, anxiety and depression are frequently discussed in patients with gliomas, but limited study focused on adult low-grade gliomas (LGG) patients with epilepsy. Hence, this study aimed to compare the prevalence of anxiety and depression in adult LGG patients with epilepsy and without epilepsy, and investigate the prognostic value of epilepsy before surgery in these patients.</div></div><div><h3>Methods</h3><div>A prospective study of 96 adult LGG patients with epilepsy, and 151 adult LGG patients without epilepsy were enrolled to measure anxiety and depression before surgery, 6 months after surgery, 12 months after surgery. All these patients were followed up to death or 36 months.</div></div><div><h3>Results</h3><div>We found that the prevalence of preoperative anxiety in adult LGG patients with epilepsy was 62.5% to 63.5%, which was higher than the prevalence of preoperative anxiety in adult LGG patients without epilepsy, which was 45.7% to 47.7%. The prevalence of preoperative depression in adult LGG patients with epilepsy was 61.5% to 62.5%, which was much higher than 47.7% to 48.3% in non-epileptic patients. We found no differences in postoperative anxiety between patients with epilepsy and without epilepsy. Epilepsy before surgery was associated with shorter progression-free survival (PFS) in adult LGG patients.</div></div><div><h3>Conclusion</h3><div>This study indicated that the prevalence of anxiety and depression were higher in adult LGG patients with epilepsy than without epilepsy. The prognostic value of epilepsy may contribute to early prevention and improvement of prognosis in adult LGG patients with epilepsy.</div></div>","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":"1863 ","pages":"Article 149737"},"PeriodicalIF":2.7,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144191509","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Characterization of tRNA-derived fragments in the small neuron-derived extracellular vesicles of Alzheimer’s disease patients","authors":"Burak I. Arioz ,&nbsp;Leman Binokay ,&nbsp;Bora Tastan ,&nbsp;Bilgesu Genc ,&nbsp;Aysen Cotuk ,&nbsp;Erdinç Dursun ,&nbsp;Duygu Gezen-Ak ,&nbsp;Hasmet Hanagası ,&nbsp;I.Hakan Gurvit ,&nbsp;Basar Bilgic ,&nbsp;Alper Bagriyanik ,&nbsp;Gökhan Karakülah ,&nbsp;Görsev G Yener ,&nbsp;Sermin Genc","doi":"10.1016/j.brainres.2025.149730","DOIUrl":"10.1016/j.brainres.2025.149730","url":null,"abstract":"<div><h3>Introduction</h3><div>Alzheimer’s disease (AD) is a progressive neurological disorder characterized by memory loss and cognitive impairment. The development of neurofibrillary tangles and amyloid plaques are pathological hallmarks of the disease. Molecular mechanisms underlying AD are multifaceted, extracellular vesicles contribute disease pathogenesis via cargo molecules such as DNA, protein, RNA and non-coding RNAs. tRNA-derived fragments (tRFs) are small non-coding RNAs with regulatory functions and their alterations have been demonstrated in various diseases. In this study, we aimed to investigate peripherally altered tRFs in small neuron-derived extracellular vesicles (sNDEVs) from AD patients.</div></div><div><h3>Method</h3><div>83 AD patients and 39 healthy controls were enrolled to study. After total sEVs isolation with ultracentrifugation, sNDEVs were enriched with CD171. EVs were characterized using Western blot, nanoparticle tracking analysis (NTA), and STEM. We utilized next-generation sequencing to analyze the expression profiles of tRFs in sNDEVs from AD patients compared to healthy controls. For the Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses, we employed the ShinyGO web tool. The alterations of two differentially expressed tRNA fragments in the sNDEVs of AD patients, were confirmed using the RT-qPCR method.</div></div><div><h3>Result</h3><div>In our study we found that three tRFs were significantly upregulated, and 10 tRFs were significantly downregulated. Then, we confirmed the upregulation of tRF-20-1HPSR9O9 and the downregulation of tRF-33-RM7KYUPRENRHD2 on a larger population with the RT-qPCR method. In the KEGG and GO analyses using targets of detected tRFs, we found significant terms related to brain and neurons, such as neuron projection morphogenesis, neuron differentiation, long-term depression and glutamatergic synapse.</div></div><div><h3>Conclusion</h3><div>Our study suggests that tRFs in sNDEVs of AD patients differ from controls and the role of these tRFs in disease pathogenesis be investigated in further studies.</div></div>","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":"1862 ","pages":"Article 149730"},"PeriodicalIF":2.7,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144170555","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A comprehensive approach to Alzheimer’s Disease: Exploring Nanotechnology, treatment Innovations, and sex differences","authors":"Lucia M. Chavez-López ,&nbsp;J. Horacio Silvestre-Martínez ,&nbsp;Karina del Carmen Lugo-Ibarra ,&nbsp;Ana B. Castro-Ceseña","doi":"10.1016/j.brainres.2025.149718","DOIUrl":"10.1016/j.brainres.2025.149718","url":null,"abstract":"<div><div>In the world, over 50 million people are living with Alzheimer’s disease (AD), and in thirty years, this number is expected to double or even exceed that. AD is a form of dementia characterized by memory loss, language difficulties, and impaired thinking skills. It involves the accumulation of beta-amyloid plaques and tau tangles in the brain, leading to neurodegeneration and disrupted neuron communication. After diagnosis, patients typically survive for four to eight years, though some may live up to 20 years. Currently, there is no cure, and the available treatment options are limited in improving the quality of patients’ lives. However, a promising perspective for treatment based on nanotechnology narrows down the possibility of personalized treatment. In this review, we explore several topics related to Alzheimer’s disease to provide a comprehensive understanding of how nanotechnology can enhance treatment approaches. We examine various types of nano treatments and delivery methods, as well as the challenges they face and their associated benefits. Additionally, we highlight current nano treatments in development and discuss improved cell and animal models that can effectively test these treatments for patient safety. We also address sex differences in the pathophysiology of Alzheimer’s disease, which may allow for more targeted treatment strategies. By considering these factors in conjunction, we move closer to realizing personalized medicine, ultimately improving the quality of life for patients. Nano treatments offer the potential for more specific, safer, and effective solutions in managing Alzheimer’s disease.</div></div>","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":"1862 ","pages":"Article 149718"},"PeriodicalIF":2.7,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144170618","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Improving brain tumor diagnosis: A self-calibrated 1D residual network with random forest integration","authors":"A. Sumithra ,&nbsp;P.M. Joe Prathap ,&nbsp;A. Karthikeyan ,&nbsp;S. Dhanasekaran","doi":"10.1016/j.brainres.2025.149704","DOIUrl":"10.1016/j.brainres.2025.149704","url":null,"abstract":"<div><div>Medical specialists need to perform precise MRI analysis for accurate diagnosis of brain tumors. Current research has developed multiple artificial intelligence (AI) techniques for the process automation of brain tumor identification. However, existing approaches often depend on singular datasets, limiting their generalization capabilities across diverse clinical scenarios. The research introduces SCR-1DResNet as a new diagnostic tool for brain tumor detection that incorporates self-calibrated Random Forest along with one-dimensional residual networks. The research starts with MRI image acquisition from multiple Kaggle datasets then proceeds through stepwise processing that eliminates noise, enhances images, and performs resizing and normalization and conducts skull stripping operations. After data collection the WaveSegNet mode l extracts important attributes from tumors at multiple scales. Components of Random Forest classifier together with One-Dimensional Residual Network form the SCR-1DResNet model via self-calibration optimization to improve prediction reliability. Tests show the proposed system produces classification precision of 98.50% accompanied by accuracy of 98.80% and recall reaching 97.80% respectively. The SCR-1DResNet model demonstrates superior diagnostic capability and enhanced performance speed which shows strong prospects towards clinical decision support systems and improved neurological and oncological patient treatments.</div></div>","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":"1862 ","pages":"Article 149704"},"PeriodicalIF":2.7,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144172743","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Characteristics of EEG microstates in stroke patients with cognitive impairment after basal ganglia injury","authors":"Weicheng Kong ,&nbsp;Xinyang Wang ,&nbsp;Jian Song ,&nbsp;Yuqing Zhao ,&nbsp;Wei Wei ,&nbsp;Yanyan Li ,&nbsp;Haoran Shi ,&nbsp;Jiayu Cai ,&nbsp;Xiehua Xue","doi":"10.1016/j.brainres.2025.149716","DOIUrl":"10.1016/j.brainres.2025.149716","url":null,"abstract":"<div><h3>Objectives</h3><div>To explore changes in Electroencephalography (EEG) microstates in patients with cognitive impairment following basal ganglia stroke to understand the neural mechanisms of cognitive deficits better.</div></div><div><h3>Methods</h3><div>Thirty post-stroke cognitive impairment (PSCI, MoCA &lt; 26, age: 60.07 ± 7.57, male/female: 22/8) patients, 23 post-stroke patients without cognitive impairment (PSN, MoCA ≥ 26, age: 59.57 ± 8.65, male/female: 17/6), and 27 healthy controls (HC, MoCA ≥ 26, age: 62.26 ± 6.65, male/female: 17/10) underwent cognitive tests and EEG recordings. EEG data were preprocessed to analyze microstate parameters, with variance testing performed across groups. Following preprocessing of the raw EEG data, global field power (GFP) was computed to identify periods of maximal topographic stability. Four prototypical microstate classes were derived using K-means clustering, after which three key temporal characteristics were quantified for each participant: (1) microstate mean duration, (2) Mean Frequency of Occurrence, and (3) Mean Coverage. Correlation analyses were conducted between microstate parameters and cognitive scores in the PSCI group. The cut-off value, sensitivity, and specificity of metrics related to overall cognitive function were calculated with the receiver operating characteristic curve.</div></div><div><h3>Results</h3><div>Cognitive assessments revealed significantly poorer performance in all domains for the PSCI group than the PSN and HC groups (p &lt; 0.001). The PSCI group exhibited a longer mean media duration (MMD) and lower incidence mean frequency of occurrence (MFO) of EEG microstates compared to other groups (p &lt; 0.01). The mean duration of microstates A, and D negatively correlated with MoCA total scores (microstates A: r = −0.491, microstates D: r = −0.372), particularly in attention and orientation domains. Furthermore, receiver operating characteristic (ROC) curve analysis indicated that the mean duration of microstate A can potentially serve as a diagnostic biomarker for PSCI. The optimal cut-off values for A-MMD were 45.41 points. The area under the curve was 0.82, sensitivity was 80 %, and specificity was 69.6 %.</div></div><div><h3>Conclusion</h3><div>Basal ganglia injury is associated with abnormal EEG microstate dynamics, characterized by prolonged microstate duration and reduced incidence rate, contributing to cognitive network dysfunction. These findings suggest EEG microstates as potential biomarkers for diagnosis.</div></div>","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":"1863 ","pages":"Article 149716"},"PeriodicalIF":2.7,"publicationDate":"2025-05-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144156880","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Crocin drives intestinal microbiota variation in a rat model of Alzheimer’s disease by reducing DKK3 expression","authors":"Xiaojia Yang ,&nbsp;Meng Jiang ,&nbsp;Min Wu ,&nbsp;Xin Jin ,&nbsp;Xinyu Wang ,&nbsp;Lan Lv ,&nbsp;Liquan Liu","doi":"10.1016/j.brainres.2025.149734","DOIUrl":"10.1016/j.brainres.2025.149734","url":null,"abstract":"<div><h3>Background</h3><div>Alzheimer’s disease (AD) is a common neurodegenerative disease. Targeting DKK3-mediated intestinal microbiota (IM) variation is a promising strategy to treat AD. Crocin can alter IM distribution and inhibit DKK3 expression. We aimed to explore whether Crocin alleviates AD by regulating DKK3-mediated IM variation.</div></div><div><h3>Methods</h3><div>AD animal models were established by injecting Aβ_1-42 into the brains of rats. Subsequently, AD rats were overexpressed with DKK3 and treated with Crocin. Morris water maze and passive avoidance tests were performed to assess the learning and memory abilities of the rats. The effect of Crocin on brain Aβ_1-42 and p-tau levels, serum proinflammatory cytokine (TNF-α, IL-1β and IL-6) levels were analyzed. Then, hippocampal pathological damage of the rats was evaluated. Furthermore, DKK3, NeuN, Bax, BCL-2 expressions and GSK-3β phosphorylation were measured by immunohistochemistry and Western blot. Moreover, rat feces were collected for 16S rRNA sequencing.</div></div><div><h3>Results</h3><div>Crocin improved learning and memory abilities of AD rats. Additionally, Crocin inhibited brain Aβ_1-42 and p-tau levels, and serum proinflammatory cytokine levels for AD rats. It was also observed that Crocin attenuated hippocampal pathological damage, inhibited DKK3, Bax expressions and GSK-3β phosphorylation, but increased NeuN, BCL-2 expressions for AD rats. Notably, Crocin increased the α and β diversity of the IM in AD rats. However, DKK3 overexpression reversed these situations. Additionally, Crocin treatment led to an increase in <em>Prevotellaceae_NK3B31_group</em>, alongside reductions in <em>Lachnospiraceae UCG-001</em> and <em>Family_XIII_AD3011_group</em>.</div></div><div><h3>Conclusion</h3><div>Crocin alleviated AD by regulating DKK3-mediated IM variation, suggesting that DKK3-mediated IM variation was a potential therapeutic target for AD.</div></div>","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":"1862 ","pages":"Article 149734"},"PeriodicalIF":2.7,"publicationDate":"2025-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144149199","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sex-specific effects of chronic fluoxetine on c-Fos expression in Murine brain regions","authors":"Minerva Ortiz-Valladares ,&nbsp;Christian Peregrino-Ramírez ,&nbsp;Ricardo Pedraza-Medina ,&nbsp;Jorge Guzmán-Muñiz ,&nbsp;Oscar Gonzalez-Perez","doi":"10.1016/j.brainres.2025.149735","DOIUrl":"10.1016/j.brainres.2025.149735","url":null,"abstract":"<div><div>Fluoxetine (FLX), a selective serotonin reuptake inhibitor, is widely prescribed for treating mood disorders. Despite its therapeutic benefits, the precise mechanisms and brain regions impacted by long-term FLX treatment remain understood. To explore this, we analyzed c-Fos immunoreactivity in brain regions associated with emotional regulation after 30-day oral FLX treatment in male and female mice. Our findings showed a significant reduction in c-Fos expression in FLX-treated groups compared to controls, suggesting decreased cellular activity in several brain regions. Furthermore, significant sex differences were observed as male mice exhibited higher c-Fos activity than females. Treatment interaction indicated FLX might reduce these sex disparities, except in the CA2 region of the hippocampus, where males maintained higher activity. Notably, FLX appeared to minimize the sex-based disparities in c-Fos expression in several regions, suggesting that FLX equalizes cellular activity across sexes in areas associated with cognitive and emotional functions. Altogether, these data indicate that FLX modulates cellular activity via a sex-dependent mechanism, which highlights the relevance of considering sex differences in the assessment of the neurobiological effects of FLX.</div></div>","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":"1862 ","pages":"Article 149735"},"PeriodicalIF":2.7,"publicationDate":"2025-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144135023","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Earthworm extract improves cerebral ischemia–reperfusion injury through regulating microglia polarization and promoting cerebral angiogenesis in vitro and in vivo","authors":"Lei Zhao ,&nbsp;Menglan Yin ,&nbsp;Meng Wang ,&nbsp;Yushuang Cao ,&nbsp;Lichen Guo ,&nbsp;Lijuan Chai ,&nbsp;Shaoxia Wang ,&nbsp;Limin Hu ,&nbsp;Qing Yuan","doi":"10.1016/j.brainres.2025.149721","DOIUrl":"10.1016/j.brainres.2025.149721","url":null,"abstract":"<div><div>Promoting the polarization of microglia towards an anti-inflammatory M2 phenotype probably be exploited as a potential strategy for stroke. While earthworm has been shown to possess anti-inflammatory effects, its potential impact on microglial polarization and post-stroke recovery remains unclear. In in vitro experiments, BV2 mouse microglial cells were stimulated with lipopolysaccharide (LPS). Then, BV2 cells were given Earthworm extract (EWE). The expression levels of microglial phenotypic markers (CD16 and CD206), as well as cytokines (including IL-1β, VEGF, IL-10, and TGFβ), were assessed using techniques such as RT-PCR, immunofluorescence, ELISA, or Western blot. Subsequently, the viability and angiogenic potential of HCMEC/D3 human endothelial cells treated with conditioned media obtained from BV2 cells exposed to EWE (EWE-CM) were evaluated using migration assay, and tube formation assay. In in vivo experiments, C57 black mouse (C57 BL/6 mice) underwent middle cerebral artery occlusion and reperfusion (MCAO/R) and received daily tail injections of EWE for a duration of three days. The pathological condition of the brain was assessed using neurological deficit scores, 2,3,5-triphenyltetrazolium chloride (TTC), hematoxylin-eosin (H&amp;E), and Nissl staining. The expression levels of CD206+/IBA-1+, CD16+/IBA-1+, and ki67+/Biotinylated LEL in the brain were assessed using immunofluorescence staining. The results demonstrated that EWE significantly suppressed pro-inflammatory cytokines and stimulated anti-inflammatory cytokines in LPS-induced microglia in vitro. Moreover, the EWE-CM enhanced the viability and tube-forming capacity of HCMEC/D3 cells, thereby promoting angiogenesis through activation of the Ang1/Tie2/Ang2 pathway. Furthermore, administration of EWE not only significantly ameliorated neurological deficits and reduced infarct volumes but also suppressed the activation of microglial cells in MCAO/R-induced mice in vivo. Thereby, EWE can modulate microglial cell M1/M2 polarization and enhance angiogenesis which is possibly activating the Ang1/Tie2/Ang2 pathway after cerebral ischemia, offering a potential therapeutic strategy for stroke.</div></div>","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":"1861 ","pages":"Article 149721"},"PeriodicalIF":2.7,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144123525","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mechanism of Rhizoma Polygonati in the treatment of Alzheimer’s disease based on network pharmacology and molecular docking","authors":"Qiong Zhou ,&nbsp;Xiaoman Huang ,&nbsp;Zihao Chen ,&nbsp;Fuwei Wang ,&nbsp;Lihua Xie ,&nbsp;Qiang Sun ,&nbsp;Jikun Du ,&nbsp;Jiantao Lin ,&nbsp;Baohong Li ,&nbsp;Li Li","doi":"10.1016/j.brainres.2025.149680","DOIUrl":"10.1016/j.brainres.2025.149680","url":null,"abstract":"<div><h3>Objective</h3><div>The therapeutic mechanisms of <em>Rhizoma Polygonati</em> (RP) on Alzheimer’s disease (AD) were explored using network pharmacology methods and <em>in vitro</em> experiments for validation.</div></div><div><h3>Materials and methods</h3><div>First, the main active ingredients and target proteins of RP were screened using Traditional Chinese Medicine Systems Pharmacology (TCMSP) and UniProt protein database. AD-related targets were predicted using the DisGeNET database. Subsequently, Protein-protein interaction (PPI) networks and core targets were analyzed using STRING. DAVID was utilized for GO annotation, while KEGG plug-in was employed to perform enrichment analysis of KEGG pathways. AutoDockTools were examined molecular docking. And the RP mechanism on AD was confirmed <em>in vitro</em> experimentation.</div></div><div><h3>Results</h3><div>Screening identified 8 active ingredients, 76 potential targets, and 3397 CE-related genes, with 58 overlapping targets. 4 target proteins were analyzed through the PPI networks. The RP and AD shared 451 GO biological process items and 150 KEGG signal pathways. Molecular docking results showed that diosgenin (Dio) had strong binding abilities to AKT1 and Caspase 3. Dio inhibited apoptosis through AKT1/Caspase 3 pathway in the glutamate-induced SH-SY5Y cells <em>in vitro</em>.</div></div><div><h3>Conclusion</h3><div>The study revealed RP’s potential mechanisms in treating AD, offering a theoretical basis for clinical use, by integrating network pharmacology with <em>in vitro</em> experiments.</div></div>","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":"1862 ","pages":"Article 149680"},"PeriodicalIF":2.7,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144141223","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}