Metabolic brain disease最新文献_第2页

Correction to: Regulation of oxygen-glucose deprivation/reperfusion‑induced inflammatory responses and M1‑M2 phenotype switch of BV2 microglia by Lobetyolin. 更正：Lobetyolin调节氧糖剥夺/再灌注诱导的炎症反应和BV2小胶质细胞M1 - M2表型开关。

IF 3.5 3区医学

Metabolic brain disease Pub Date : 2025-09-18 DOI: 10.1007/s11011-025-01703-w

Jie Wang, Xin Liu, Wenyi Wei, Jing Yang, Qinqing Li, Shifeng Chu, Pulin Liu, Junlong Zhang, Wenbin He

引用次数: 0

A novel modulator of the Axin/β-Catenin interaction to restore EAAT2 expression in alzheimer's disease: an in-silico and in-vitro approach. 一种新的Axin/β-Catenin相互作用调节剂，可恢复阿尔茨海默病中EAAT2的表达：一种计算机和体外方法

IF 3.5 3区医学

Metabolic brain disease Pub Date : 2025-09-16 DOI: 10.1007/s11011-025-01665-z

Harminder Kaur, Biman Saikia, Gajendra Choudhary, Manisha Prajapat, Ketaki Ghosh, Subrata Ghosh, Prasenjit Mondal, Ajay Prakash, Bikash Medhi

{"title":"A novel modulator of the Axin/β-Catenin interaction to restore EAAT2 expression in alzheimer's disease: an in-silico and in-vitro approach.","authors":"Harminder Kaur, Biman Saikia, Gajendra Choudhary, Manisha Prajapat, Ketaki Ghosh, Subrata Ghosh, Prasenjit Mondal, Ajay Prakash, Bikash Medhi","doi":"10.1007/s11011-025-01665-z","DOIUrl":"10.1007/s11011-025-01665-z","url":null,"abstract":"Alzheimer's disease (AD) is a progressive neurodegenerative disorder marked by synaptic dysfunction and neuronal loss, with glutamate excitotoxicity playing a central role in its pathology. The astrocytic glutamate transporter EAAT2, responsible for maintaining synaptic glutamate homeostasis, is significantly downregulated in AD. Restoration of EAAT2 expression presents a promising therapeutic strategy. This study explores the potential of modulating the Wnt/β-catenin signaling pathway to enhance EAAT2 levels by targeting the Axin-1/β-catenin interaction. Through virtual screening of 120,993 compounds from the Asinex-CNS database, five lead candidates were identified based on molecular docking, MMGBSA scores, and drug-likeness parameters. Advanced in-silico analyses-including Principal Component Analysis, Dynamic Cross-Correlation Mapping, molecular dynamics simulations, and MM/PBSA binding free energy calculations-highlighted BAS 04937103 as the most promising compound for disrupting β-catenin degradation. In vitro validation using C6 glioma cells and primary astrocytic cultures demonstrated that BAS 04937103 enhanced β-catenin stabilization and nuclear translocation, reduced Axin-1 expression, and significantly upregulated EAAT2 levels. These molecular effects corresponded with decreased extracellular glutamate concentrations, improved glutamate uptake, and reduced oxidative stress. Collectively, these findings establish BAS 04937103 as a novel modulator of the Axin/β-catenin interaction with therapeutic potential in mitigating glutamate-mediated neurotoxicity in Alzheimer's disease.","PeriodicalId":18685,"journal":{"name":"Metabolic brain disease","volume":"40 7","pages":"268"},"PeriodicalIF":3.5,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145070072","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Curcumin treatment reduces motor impairments and protects against rotenone-induced neurodegeneration in a rat model of Parkinson disease. 姜黄素治疗可减少帕金森病大鼠模型的运动损伤并防止鱼藤酮诱导的神经变性。

IF 3.5 3区医学

Metabolic brain disease Pub Date : 2025-09-15 DOI: 10.1007/s11011-025-01698-4

L V Darbinyan, L E Hambardzumyan, L P Manukyan, M H Danielyan, K V Karapetyan, V H Sarkisian, K V Simonyan

{"title":"Curcumin treatment reduces motor impairments and protects against rotenone-induced neurodegeneration in a rat model of Parkinson disease.","authors":"L V Darbinyan, L E Hambardzumyan, L P Manukyan, M H Danielyan, K V Karapetyan, V H Sarkisian, K V Simonyan","doi":"10.1007/s11011-025-01698-4","DOIUrl":"10.1007/s11011-025-01698-4","url":null,"abstract":"Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by degeneration of dopaminergic neurons, leading to motor impairments (bradykinesia, rigidity, tremor) and non-motor symptoms (cognitive decline, psychiatric disturbances). This study investigated the neuroprotective effects of curcumin in a rotenone-induced PD rat model. Male albino rats received daily intraperitoneal injections of rotenone (2 mg/kg) and/or curcumin (200 mg/kg) for 9 weeks. Behavioral assessments revealed that curcumin treatment significantly improved motor function, reducing catalepsy duration and increasing rearing frequency in cylinder tests. Histological analysis showed curcumin preserved neuronal density in both hippocampal and pedunculopontine nucleus (PPN) regions. Electrophysiological recordings showed that that curcumin modulated hippocampal responses to PPN high-frequency stimulation (100 Hz). These results suggest curcumin exerts multimodal neuroprotection by preserving neuronal integrity and stabilizing hippocampal-PPN circuitry. While our findings highlight curcumin's therapeutic potential, further studies quantifying synaptic markers and direct LTP measurements are needed to fully elucidate its effects on synaptic plasticity.","PeriodicalId":18685,"journal":{"name":"Metabolic brain disease","volume":"40 7","pages":"267"},"PeriodicalIF":3.5,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145065308","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Impact of agmatine on cerebral astrocyte reactivity, neurodegeneration, and oxidative stress in bile duct-ligated rats. 胍丁胺对胆管结扎大鼠脑星形胶质细胞反应性、神经变性和氧化应激的影响。

IF 3.5 3区医学

Metabolic brain disease Pub Date : 2025-09-12 DOI: 10.1007/s11011-025-01704-9

Sepideh Ganjalikhan-Hakemi, Majid Asadi-Shekaari, Turaj Reza Mirshekari, Fahimeh Pourjafaria, Masoumeh Nozari

{"title":"Impact of agmatine on cerebral astrocyte reactivity, neurodegeneration, and oxidative stress in bile duct-ligated rats.","authors":"Sepideh Ganjalikhan-Hakemi, Majid Asadi-Shekaari, Turaj Reza Mirshekari, Fahimeh Pourjafaria, Masoumeh Nozari","doi":"10.1007/s11011-025-01704-9","DOIUrl":"10.1007/s11011-025-01704-9","url":null,"abstract":"Hepatic encephalopathy (HE) is a severe neurological disorder arising from liver disease, often studied using the bile duct ligation (BDL) model. This condition leads to cholestasis, triggering oxidative stress, liver damage, and fibrosis. Agmatine (AGM), an endogenous polyamine known for its neuroprotective effects, has shown potential in treating various neurological and psychological disorders due to its anti-inflammatory and antioxidant properties. This study investigates the potential of AGM to mitigate liver and brain injury in a rat model of BDL-induced HE. Adult male Wistar rats were divided into four groups: a Sham group, a BDL group, and two BDL + AGM groups (receiving 40 mg/kg and 80 mg/kg AGM, respectively). AGM was administered via oral gavage, starting from the second week post-surgery and continuing for four weeks. At the end of the study, the animals were sacrificed; brain and liver tissues, along with blood samples, were collected for analysis. Glial fibrillary acidic protein (GFAP) immunohistochemistry staining was performed to assess astrocyte reactivity. Brain oxidative stress, liver function, and fibrosis were assessed. The BDL animals exhibited significantly increased liver damage markers, liver tissue fibrosis, and brain oxidative stress markers. Astrogliosis was evident in the hippocampus of BDL rats. However, AGM treatment ameliorated these effects, improving superoxide dismutase (SOD) and Malonaldehyde (MDA) levels, and reducing liver dysfunction. AGM also reduced hippocampal astrogliosis and cerebellar Purkinje cell degeneration in BDL rats. These findings suggest that AGM holds potential as a therapeutic agent for mitigating liver and brain damage associated with hepatic encephalopathy.","PeriodicalId":18685,"journal":{"name":"Metabolic brain disease","volume":"40 7","pages":"266"},"PeriodicalIF":3.5,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145040699","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

4-aminopyridine exerts anxiolytic and pro-cognitive effects in mice model of medial prefrontal cortex ischemia. 4-氨基吡啶对小鼠内侧前额叶皮质缺血模型具有抗焦虑和促认知作用。

IF 3.5 3区医学

Metabolic brain disease Pub Date : 2025-09-10 DOI: 10.1007/s11011-025-01695-7

Esmaeil Imani-Almas, Javad Mahmoudi, Mehdi Farhoudi, Saeed Sadigh-Eteghad, Abbas Ebrahimi-Kalan

{"title":"4-aminopyridine exerts anxiolytic and pro-cognitive effects in mice model of medial prefrontal cortex ischemia.","authors":"Esmaeil Imani-Almas, Javad Mahmoudi, Mehdi Farhoudi, Saeed Sadigh-Eteghad, Abbas Ebrahimi-Kalan","doi":"10.1007/s11011-025-01695-7","DOIUrl":"https://doi.org/10.1007/s11011-025-01695-7","url":null,"abstract":"Brain ischemia is a major global cause of disability, frequently leading to psychoneurological issues. This study investigates the effects of 4-aminopyridine (4-AP) on anxiety, cognitive impairment, and potential underlying mechanisms in a mouse model of medial prefrontal cortex (mPFC) ischemia. Mice with mPFC ischemia were treated with normal saline (NS) or different doses of 4-AP (250, 500, and 1000 µg/kg) for 14 consecutive days. The open field test, elevated plus maze, Barnes maze, and novel object recognition test were used to perform a series of behavioral assessments to evaluate anxiety as well as spatial and episodic memory. Serum corticosterone levels and changes in oxidative stress markers (MDA, SOD, GPx, and TAC) were measured by ELISA. Inflammatory and apoptotic markers (p-P38, NF-κB, IL-1β, TNF-α, p-PI3K, p-AKT, Caspase-3, BAX, and BCL2) were analyzed via western blotting. Results showed that mPFC ischemia induced anxiety-like behavior and disrupted both recognition and spatial memory at the behavioral level. Additionally, ischemia increased serum corticosterone levels, elevated oxidative stress, and upregulated inflammatory and apoptotic markers. However, 4-AP at the highest dose significantly mitigated these behavioral and molecular deficits. These findings suggest that 4-AP alleviates anxiety-like behavior and cognitive impairment associated with mPFC ischemia, possibly through modulation of corticosterone, oxidative stress, inflammation, and apoptotic signaling pathways.","PeriodicalId":18685,"journal":{"name":"Metabolic brain disease","volume":"40 7","pages":"264"},"PeriodicalIF":3.5,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145030198","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Simple scoring model for predicting overt hepatic encephalopathy in geriatric cirrhosis: A multicenter retrospective cohort study. 预测老年肝硬化明显肝性脑病的简单评分模型：一项多中心回顾性队列研究。

IF 3.5 3区医学

Metabolic brain disease Pub Date : 2025-09-10 DOI: 10.1007/s11011-025-01691-x

Yuki Utakata, Takao Miwa, Masashi Aiba, Shinji Unome, Tatsunori Hanai, Kenji Imai, Yohei Shirakami, Koji Takai, Makoto Shiraki, Naoki Katsumura, Masahito Shimizu

{"title":"Simple scoring model for predicting overt hepatic encephalopathy in geriatric cirrhosis: A multicenter retrospective cohort study.","authors":"Yuki Utakata, Takao Miwa, Masashi Aiba, Shinji Unome, Tatsunori Hanai, Kenji Imai, Yohei Shirakami, Koji Takai, Makoto Shiraki, Naoki Katsumura, Masahito Shimizu","doi":"10.1007/s11011-025-01691-x","DOIUrl":"10.1007/s11011-025-01691-x","url":null,"abstract":"Identifying the risk of overt hepatic encephalopathy (OHE) in geriatric patients with cirrhosis remains challenging. This study aimed to investigate the independent factors for OHE development in geriatric cirrhosis and to establish a simple scoring model to identify individuals at risk for OHE. We conducted a retrospective review of geriatric patients with cirrhosis aged ≥ 80 years who were admitted between April 2006 and November 2022. Baseline parameters were assessed at the time of admission, and factors associated with OHE development were examined using Fine-Gray proportional hazards regression analysis, with mortality as a competing risk. Based on the factors associated with OHE development, a simple hepatic encephalopathy (sHE) score was calculated, and its efficacy was subsequently verified. Of the 270 patients analyzed, the median age was 83 years, and 63% were male. During a median follow-up of 1.8 years, 41 (15%) patients developed OHE and 120 (44%) patients died. Multivariable analysis revealed that serum albumin (sub-distribution hazard ratio [SHR], 0.51; 95% confidence interval [CI], 0.27-0.98; p = 0.042) and ammonia (SHR, 1.01; 95% CI, 1.00-1.02; p = 0.006) levels were independent factors for OHE development in geriatric cirrhosis. Based on the sHE score, the high-risk and intermediate-risk groups exhibited a high incidence of OHE, whereas those in the low-risk group rarely developed OHE. Serum albumin and ammonia levels were identified as independent risk factors for the development of OHE in geriatric cirrhosis. The sHE score was useful for stratifying the risk of OHE in the geriatric population.","PeriodicalId":18685,"journal":{"name":"Metabolic brain disease","volume":"40 7","pages":"263"},"PeriodicalIF":3.5,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12423195/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145030122","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Transformations in plasma metabolic profiles of patients with major depression disorder during treatment. 重度抑郁症患者治疗期间血浆代谢谱的变化

IF 3.5 3区医学

Metabolic brain disease Pub Date : 2025-09-10 DOI: 10.1007/s11011-025-01682-y

Yujing Du, Xixuan Li, Shufang Zhang, Jingxuan Tan, Ying Zhu, Xuejia Zhai, Yongning Lu

{"title":"Transformations in plasma metabolic profiles of patients with major depression disorder during treatment.","authors":"Yujing Du, Xixuan Li, Shufang Zhang, Jingxuan Tan, Ying Zhu, Xuejia Zhai, Yongning Lu","doi":"10.1007/s11011-025-01682-y","DOIUrl":"https://doi.org/10.1007/s11011-025-01682-y","url":null,"abstract":"Major depression disorder (MDD) is a mental condition that significantly threatens both physical and psychological health. This study aimed to discern variances in plasma metabolic profiles between MDD sufferers and healthy counterparts. Additionally, we tracked the hospitalization journey of MDD patients to investigate the normalization of metabolic irregularities through conventional treatment in the form of self-control. Ultra-Performance Liquid Chromatography - Mass Spectrometry was employed to analyze the metabolic profiles of 47 plasma samples, including 12 controls and 12 MDD patients at three distinct clinical stages (untreated baseline, 1-month post-treatment, and 2-month post-treatment). Multivariate statistical analysis and K-means clustering were executed to pinpoint significantly different metabolites between the groups and specific metabolites showing an ideal trend of variation. Subsequently, these metabolites were mapped onto Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways to preliminarily explore the potential mechanism of metabolic shifts in MDD. We identified 14 significantly different metabolites between MDD patients and controls. Among these, the relative levels of 9-hydroperoxy octadecadienoic acid, imidazoleacetic acid, thromboxane B2, and arachidonic acid displayed a regular trend of variation post-treatment. Further integration analysis yielded a novel metabolite-pathway network comprising these 4 specific metabolites and 8 pathways. These findings suggest that transitions in metabolic pathways during the onset and treatment of MDD are primarily governed by lipid metabolism and its associated signaling pathway system, with the involvement of histidine metabolism. The identified metabolites hold promise for diagnosing and evaluating the therapeutic efficacy of MDD, and provide a foundation for future research into the potential mechanisms underlying MDD.","PeriodicalId":18685,"journal":{"name":"Metabolic brain disease","volume":"40 7","pages":"265"},"PeriodicalIF":3.5,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145030127","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Multimodal evaluation of nitazoxanide as an antidepressant: behavioral, biochemical, and molecular docking insights. nitazoxanide作为抗抑郁药的多模式评价：行为，生化和分子对接见解。

IF 3.5 3区医学

Metabolic brain disease Pub Date : 2025-09-09 DOI: 10.1007/s11011-025-01680-0

Muqtada Shaikh, Akshata Pahelkar, Gaurav Doshi

{"title":"Multimodal evaluation of nitazoxanide as an antidepressant: behavioral, biochemical, and molecular docking insights.","authors":"Muqtada Shaikh, Akshata Pahelkar, Gaurav Doshi","doi":"10.1007/s11011-025-01680-0","DOIUrl":"https://doi.org/10.1007/s11011-025-01680-0","url":null,"abstract":"This study aimed to evaluate the antidepressant potential of Nitazoxanide (NTZ), an antiprotozoal drug with known anti-inflammatory and neuroprotective properties, in a chronic unpredictable mild stress (CUMS)-induced mice model of depression. NTZ was administered at doses of 75, 150, and 300 mg/kg, and its effects were assessed through a series of behavioral tests, including the forced swim test, tail suspension test, actophotometer test, and social interaction test. NTZ treatment at 150 and 300 mg/kg significantly improved behavioral and biochemical outcomes, relieving depressive-like symptoms and restoring neurochemical balance. Significant relief of depressive-like symptoms was observed following NTZ treatment. To understand the underlying mechanisms, we examined the modulation of neuroinflammatory and neurotransmitter pathways. NTZ treatment increased phosphoinositide 3-kinase (PI3K) and serotonin (5-HT) levels while decreasing pro-inflammatory markers such as nuclear factor kappa B (NF-κB) and interleukin-1 beta (IL-1β), indicating potent anti-inflammatory and neuroprotective effects. Additionally, molecular docking analysis confirmed NTZ's effective binding affinity to depression-related target proteins 8DP0 and 1K3Z, with binding energies of - 11.81 and 29.878 kcal/mol, respectively. These findings indicate that modulation of the PI3K/Akt/NF-κB signaling pathway mediates NTZ's antidepressant effects. Overall, our study provides compelling evidence that NTZ produces significant antidepressant activity by targeting key inflammatory and neuroprotective pathways, highlighting its potential as a novel therapeutic option for depression and supporting the need for further long-term studies to evaluate its efficacy and safety.","PeriodicalId":18685,"journal":{"name":"Metabolic brain disease","volume":"40 7","pages":"262"},"PeriodicalIF":3.5,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145023767","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The therapeutic effects of various tonic traditional Chinese medicines on demyelinating diseases. 各种补益中药对脱髓鞘性疾病的治疗作用。

IF 3.5 3区医学

Metabolic brain disease Pub Date : 2025-09-09 DOI: 10.1007/s11011-025-01702-x

Cunming Lv, Qiang Li, Jinhao Chen

{"title":"The therapeutic effects of various tonic traditional Chinese medicines on demyelinating diseases.","authors":"Cunming Lv, Qiang Li, Jinhao Chen","doi":"10.1007/s11011-025-01702-x","DOIUrl":"https://doi.org/10.1007/s11011-025-01702-x","url":null,"abstract":"Demyelinating diseases, a prevalent group of neurological disorders, lead to impaired nerve conduction and sensorimotor dysfunctions. Despite existing treatments demonstrating some efficacy, their limitations have driven research toward exploring natural remedies. This review summarizes the therapeutic potential of four traditional tonic Chinese herbal medicines-ginsenosides, deer antler polypeptides, resveratrol, and ginkgo leaf extracts-for demyelinating diseases. The selection of these four components is based on their reported neuroprotective and immunomodulatory effects in recent studies. Ginsenosides can modulate immune functions, counteract oxidative stress, and promote remyelination in demyelinating injuries caused by inflammatory conditions. Deer antler polypeptides facilitate remyelination by regulating the expression of myelin-related proteins. Resveratrol exhibits antioxidant and anti-inflammatory properties, alleviating the symptoms of chronic demyelinating diseases induced by metabolic disturbances. Among the components of ginkgo leaf extracts, flavonoids protect neurons and inhibit apoptosis, while terpene lactones modulate the expression of myelin-related genes. This review summarizes the current research on these tonic Chinese herbal medicines and discusses their potential applications in treating demyelinating diseases. This comprehensive review evaluates the research progress on these essential tonic Chinese herbal medicines, revealing their potential applications in demyelinating disease treatments. It may offer a basis for future investigations and potential implications for clinical research.","PeriodicalId":18685,"journal":{"name":"Metabolic brain disease","volume":"40 7","pages":"261"},"PeriodicalIF":3.5,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145023753","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

TLR-4/Notch1/NF-κB pathway modulation by dapagliflozin: a novel mechanism for neuroprotection in hepatic encephalopathy. 达格列净调节TLR-4/Notch1/NF-κB通路：肝性脑病神经保护的新机制

IF 3.5 3区医学

Metabolic brain disease Pub Date : 2025-09-08 DOI: 10.1007/s11011-025-01681-z

Hossam H Abouzaid, Muhammed F El-Yamany, Yasser O Mosaad, Mohamed M Sayed-Ahmed, Riham M Karkeet, Ayman E El-Sahar

{"title":"TLR-4/Notch1/NF-κB pathway modulation by dapagliflozin: a novel mechanism for neuroprotection in hepatic encephalopathy.","authors":"Hossam H Abouzaid, Muhammed F El-Yamany, Yasser O Mosaad, Mohamed M Sayed-Ahmed, Riham M Karkeet, Ayman E El-Sahar","doi":"10.1007/s11011-025-01681-z","DOIUrl":"10.1007/s11011-025-01681-z","url":null,"abstract":"Acute or chronic liver damage can result in Hepatic Encephalopathy (HE), a potentially fatal neuropsychiatric condition that leads to cerebral and neurological alterations. Dapagliflozin (DAPA), an orally active Sodium/Glucose cotransporter 2 inhibitor with long duration of action. The study aim was to evaluate the potential protective impact of DAPA against HE caused by Thioacetamide (TAA) in rats. HE was achieved via a single intraperitoneal TAA dosage of (300 mg/kg). DAPA was administered orally as (1 mg/kg) for 28 days. A total of forty rats were distributed randomly into 4 equal groups: Control (CTRL), Dapagliflozin (DAPA + CTRL), Thioacetamide (TAA), and Dapagliflozin plus Thioacetamide (DAPA + TAA). TAA induced cognitive impairment was alleviated by DAPA, as evidenced by reduction by 63% in escape latency of Morris water maze (MWM) test, elevation in fall off period of Rotarod test, and reduced serum ammonia, Liver enzymes, and restore normal serum albumin levels. DAPA improved the antioxidant capacity and activity of Glutathione by 87.53%; reduced apoptosis, liver necrosis, and astrocyte inflammation. Moreover, DAPA administration reduced gene expression of both Notch1 by 50% and TLR-4 by 55.65% suppressing release of inflammatory cytokines. In conclusion, DAPA possesses a neuroprotective effect, as confirmed by the enhancement of motor incoordination, cognitive deficits, and histopathological alterations. This neuroprotective impact can be justified by lowering hyperammonemia, improving liver functions, in addition to its antioxidant effect, and suppression of TLR-4/Notch1/NF-κB inflammatory pathway.","PeriodicalId":18685,"journal":{"name":"Metabolic brain disease","volume":"40 7","pages":"260"},"PeriodicalIF":3.5,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12417255/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145015756","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0