European journal of pharmacology最新文献_第7页

TBB inhibits CK2/PD-L1/EGFR pathway-mediated tumor progression TBB抑制CK2/PD-L1/EGFR途径介导的肿瘤进展

IF 4.2 3区医学

European journal of pharmacology Pub Date : 2025-04-29 DOI: 10.1016/j.ejphar.2025.177689

Suning Che, Yao Zhang, Huihui Xu, Juanjuan Shi, Yongzhong Hou

引用次数: 0

Molecular mechanisms and therapeutic perspectives of luteolin on diabetes and its complications 木犀草素治疗糖尿病及其并发症的分子机制及治疗前景

IF 4.2 3区医学

European journal of pharmacology Pub Date : 2025-04-29 DOI: 10.1016/j.ejphar.2025.177691

Qingzhi Liang , Xiaoqin Liu , Xin Xu , Zhengtao Chen , Ting Luo , Yi Su , Chunguang Xie

{"title":"Molecular mechanisms and therapeutic perspectives of luteolin on diabetes and its complications","authors":"Qingzhi Liang , Xiaoqin Liu , Xin Xu , Zhengtao Chen , Ting Luo , Yi Su , Chunguang Xie","doi":"10.1016/j.ejphar.2025.177691","DOIUrl":"10.1016/j.ejphar.2025.177691","url":null,"abstract":"<div><h3>Background</h3><div>Extensive preclinical studies have established luteolin, a flavonoid with potent antidiabetic activity, as a therapeutic candidate for preventing and managing various diabetic complications including cardiomyopathy, nephropathy, and osteopathy. This systematic review evaluates current evidence regarding luteolin's antidiabetic potential.</div></div><div><h3>Aim of the study</h3><div>This study evaluates luteolin's efficacy in diabetes management through evidence synthesis, while critically assessing current research challenges and translational opportunities.</div></div><div><h3>Methods</h3><div>A comprehensive literature search was conducted across Pubmed, Embase, Web of Science, and Google Scholar databases, encompassing articles published between 2000 and 2024.</div></div><div><h3>Results</h3><div>Luteolin is a naturally occurring flavonoid that has strong antidiabetic properties. It regulates intestinal microenvironmental homeostasis, lipogenesis and catabolism, and the absorption of carbohydrates. It also modulates nine diabetic complications by reducing inflammation, oxidative stress, apoptosis, and autophagy. Luteolin's potential nutritional and physiological benefits notwithstanding, attention must be directed immediately to its bioavailability, innovative formulations, safety assessment, synergistic effects, and optimal dosage and time for supplementation. In particular, clinical studies are needed to validate efficacy and safety and provide a reliable scientific basis.</div></div><div><h3>Conclusion</h3><div>Luteolin may act as a pleiotropic molecule targeting multiple signaling cascades to exert antidiabetic bioactivity.</div></div>","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":"1000 ","pages":"Article 177691"},"PeriodicalIF":4.2,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143937100","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

Genkwanin blocks the interaction between phosphorylated JNK and NFATc1 to promote osteogenic differentiation and collagen Ⅰ α1 production Genkwanin阻断磷酸化JNK与NFATc1的相互作用，促进成骨分化和胶原Ⅰα1的产生

IF 4.2 3区医学

European journal of pharmacology Pub Date : 2025-04-29 DOI: 10.1016/j.ejphar.2025.177687

Yu-Xuan Hao , Yong-yan Chen , Xu Han , Xu Wang , Fu-peng Wu , Cai-ling Wen , Tong-qing Chen , Sheng Tan , Dan-dan Zheng , Yang Hong , Xiao-yan Shen

{"title":"Genkwanin blocks the interaction between phosphorylated JNK and NFATc1 to promote osteogenic differentiation and collagen Ⅰ α1 production","authors":"Yu-Xuan Hao , Yong-yan Chen , Xu Han , Xu Wang , Fu-peng Wu , Cai-ling Wen , Tong-qing Chen , Sheng Tan , Dan-dan Zheng , Yang Hong , Xiao-yan Shen","doi":"10.1016/j.ejphar.2025.177687","DOIUrl":"10.1016/j.ejphar.2025.177687","url":null,"abstract":"<div><div>Genkwanin (GWA), a flavonoid compound found abundantly in various traditional Chinese medicines, has demonstrated pharmacological effectiveness against a range of diseases. However, its role in bone formation and the underlying mechanisms remain to be elucidated. The aim of this study is to investigate the effects of GWA on osteogenic differentiation and to uncover the possible mechanisms. Primary bone marrow-derived mesenchymal stem cells (BMSCs) and MC3T3-E1 cells induced for osteogenic differentiation were used as in vitro cell models. An ovariectomy (OVX) mouse model to induce secondary osteoporosis was used to evaluate the in vivo pharmacologic efficacy of GWA. Our studies revealed that GWA facilitated osteogenic differentiation and bio-mineralization of BMSCs and MC3T3-E1 cells in vitro, and could effectively prevent OVX-induced systematic bone loss and collagen Ⅰ α1 (COL1A1) reduction in vivo. Mechanism studies indicated that GWA could directly bind to phosphorylated c-Jun N-terminal kinase (pJNK) to prevent the phosphorylation of nuclear factor of activated T cells 1 (NFATc1) by JNK, thereby promote osteogenic differentiation and COL1A1 production via increasing the nuclear localization of NFATc1. This is distinct from the previously recognized function of the JNK/AP-1/NFATc1 signaling pathway in activating osteoclast differentiation. More importantly, GWA had no significant effects on estrogen-related signaling pathways, indicating a unique advantage in lowering the risk of gynecological cancer. In conclusion, our data suggest that GWA may be a promising candidate for the therapy of diseases associated with bone loss. Targeting pJNK-NFATc1 interaction may represent a new strategy to stimulate osteogenesis.</div></div>","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":"999 ","pages":"Article 177687"},"PeriodicalIF":4.2,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143913125","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

Neuroregulation of histamine of circadian rhythm disorder induced by chronic intermittent hypoxia 慢性间歇性缺氧所致昼夜节律障碍中组胺的神经调节作用

IF 4.2 3区医学

European journal of pharmacology Pub Date : 2025-04-29 DOI: 10.1016/j.ejphar.2025.177662

Liang Xie , Qinhan Wu , Huai Huang , Kexin Wang , Kelu Ying , Zilong Liu , Shanqun Li

{"title":"Neuroregulation of histamine of circadian rhythm disorder induced by chronic intermittent hypoxia","authors":"Liang Xie , Qinhan Wu , Huai Huang , Kexin Wang , Kelu Ying , Zilong Liu , Shanqun Li","doi":"10.1016/j.ejphar.2025.177662","DOIUrl":"10.1016/j.ejphar.2025.177662","url":null,"abstract":"<div><div>Obstructive sleep apnea (OSA) is characterized by intermittent hypoxemia, sleep fragmentation, and excessive daytime sleepiness. OSA patients are at an elevated risk for circadian rhythm disturbances. Histamine is known to regulate the sleep-wake cycle predominantly via histamine H1 receptors. We utilized a C57BL/6 mouse model exposed to chronic intermittent hypoxia (CIH) for three weeks to assess alterations in circadian rhythmicity. Sleep architecture and voluntary wheel-running activity were evaluated. Additionally, c-fos expression and mPer2 levels in the frontal cortex (FC) and the suprachiasmatic nucleus (SCN) were examined. BV-2 microglial cells were subjected to intermittent hypoxia (IH) for 12 h to explore the underlying signaling pathways.</div><div>CIH exposure led to a significant prolongation of the wake phase and a reduction in the Non-rapid eye movement (NREM) phase, accompanied by increased sleep fragmentation and disruption of circadian rhythms. Treatment with mepyramine, an H1 receptor antagonist, mitigated these effects by reducing arousal duration, extending NREM phase, and decreasing sleep fragmentation. CIH also resulted in increased c-fos expression and elevated mPer2 levels in the FC and SCN, both of which were reversed following mepyramine administration. In vitro studies on BV-2 cells demonstrated that histamine exerts its modulatory effects through the activation of the PLC and PKA signaling pathways, influencing mPer2 expression via the regulation of K+, Na + -Ca2+, and Ca2+ ion channels.</div><div>In conclusion, CIH disrupts circadian rhythms through histamine-mediated mechanisms, and mepyramine effectively ameliorates these disruptions. These findings highlight histamine as a promising therapeutic target for addressing circadian rhythm disorders associated with OSA.</div></div>","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":"999 ","pages":"Article 177662"},"PeriodicalIF":4.2,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143913126","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

Effects of acamprosate on alprazolam-induced conditioned place preference in male rats: The role of GABA and NMDA receptor subunits 阿坎前列酸对阿普唑仑诱导的雄性大鼠条件位置偏好的影响：GABA和NMDA受体亚基的作用

IF 4.2 3区医学

European journal of pharmacology Pub Date : 2025-04-28 DOI: 10.1016/j.ejphar.2025.177643

Nasim Nadi Moghadam , Anahita Torkaman-Boutorabi , Ali Farhoudian , Emran Mohammad Razaghi

{"title":"Effects of acamprosate on alprazolam-induced conditioned place preference in male rats: The role of GABA and NMDA receptor subunits","authors":"Nasim Nadi Moghadam , Anahita Torkaman-Boutorabi , Ali Farhoudian , Emran Mohammad Razaghi","doi":"10.1016/j.ejphar.2025.177643","DOIUrl":"10.1016/j.ejphar.2025.177643","url":null,"abstract":"<div><div>Alprazolam, a commonly prescribed benzodiazepine (BZD), poses a risk for abuse and has been linked to conditioned place preference (CPP). Research indicates that effective long-term treatments for alprazolam misuse are lacking. The mechanisms of tolerance and dependence for BZDs are similar to those seen with alcohol, involving gamma-aminobutyric acid (GABA) and glutamate neurotransmitter systems. Additionally, managing withdrawal symptoms and reducing relapse rates may be identical for both substances. Acamprosate's ability to reduce alcohol cravings and relapse has led this study to explore its potential as a treatment for the extinction and reinstatement of alprazolam-induced CPP. Accordingly, we evaluated the effects of different doses of acamprosate on the extinction period and reinstatement of alprazolam-induced CPP in male rats. We also assessed hippocampal gene expression of GABA<sub>A</sub> receptor (α1, α5, γ2) subunits and N-methyl-D-aspartate (NMDA) receptor (NR1, NR2A, NR2B) subunits after reinstatement, given alprazolam's action on these receptors. Alprazolam (1.5 mg/kg) could induce CPP in a 14-day paradigm. Acamprosate (20, 50, and 100 mg/kg) attenuated alprazolam-induced extinction period and reinstatement (P < 0.01). At the molecular level, acamprosate reduced the gene expression of α1 (P < 0.05) while increased α5 and γ2 subunits of GABA<sub>A</sub> receptors (p < 0.01). Besides, the gene expression of NR1, NR2A, and NR2B subunits of NMDA receptors were significantly enhanced by acamprosate (P < 0.001). These findings suggest that acamprosate is able to reduce the duration of extinction and reinstatement of alprazolam-induced CPP in male rats.</div></div>","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":"999 ","pages":"Article 177643"},"PeriodicalIF":4.2,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143899824","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

Fluorescence-based method for analysis of glycine receptor alpha 3 agonists 甘氨酸受体α 3激动剂的荧光分析方法

IF 4.2 3区医学

European journal of pharmacology Pub Date : 2025-04-28 DOI: 10.1016/j.ejphar.2025.177661

Mikaela M. Ceder, Aikeremu Ahemaiti, Malin C. Lagerström

{"title":"Fluorescence-based method for analysis of glycine receptor alpha 3 agonists","authors":"Mikaela M. Ceder, Aikeremu Ahemaiti, Malin C. Lagerström","doi":"10.1016/j.ejphar.2025.177661","DOIUrl":"10.1016/j.ejphar.2025.177661","url":null,"abstract":"<div><div>Glycine, a key neurotransmitter, plays a complex role in the central nervous system (CNS). It acts as an inhibitory neurotransmitter by interacting with ligand-gated chloride channels. Glycine plays a crucial role in pain and itch transmission through its interactions with the glycine receptor alpha 1 (Glyr α1) and 3 (Glyr α3) subunits. Targeting glycinergic neurotransmission in the CNS, particularly the spinal cord, could provide a beneficial strategy for analgesic and/or abirritant drug discovery. Currently, the search for novel pharmacological agonists and modulators against glycine receptors is still in its early stages.</div><div>In this study, we designed two different vectors to express the human hetero-pentameric GlyR α3β. We tested different chemical transfection protocols and performed fluorescence endpoint measurements in acutely transfected cells and cells that underwent antibiotic selection. We further validated our findings by studying the electrophysiological properties of the vector-expressing cells using patch clamp.</div><div>The results demonstrate that acutely vector-transfected cells and vector-transfected cells subjected to antibiotic selection work equally well during fluorescence-based measurements. However, in single-cell measurements such as patch clamp, acutely transfected cells perform better. The results further show that reversing the equilibrium potential of [Cl-] can enhance the fluorescence response from the FluoVolt™ membrane potential dye, which can be used during patch clamp measurements. This establishes a simple and cost-effective method to screen for compounds in cell cultures using chemical transfection with a vector expressing GlyR α3β, which could aid in developing the next generation of non-opioid analgesic.</div></div>","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":"999 ","pages":"Article 177661"},"PeriodicalIF":4.2,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143904240","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

Luteolin mitigates renal ischemia-reperfusion injury via anti-inflammatory, anti-apoptotic, and Nrf2/HO-1-mediated antioxidant effects 木犀草素通过抗炎、抗凋亡和Nrf2/ ho -1介导的抗氧化作用减轻肾缺血再灌注损伤

IF 4.2 3区医学

European journal of pharmacology Pub Date : 2025-04-28 DOI: 10.1016/j.ejphar.2025.177676

Ji-Ping Wei , Bo Zhao , Zi-Jian Jiang , Peng-Yu Wang , Yan Xu , Ning Ding , Yuan-Yuan Hu , Wei Wang , Bo-Tao Jiang

{"title":"Luteolin mitigates renal ischemia-reperfusion injury via anti-inflammatory, anti-apoptotic, and Nrf2/HO-1-mediated antioxidant effects","authors":"Ji-Ping Wei , Bo Zhao , Zi-Jian Jiang , Peng-Yu Wang , Yan Xu , Ning Ding , Yuan-Yuan Hu , Wei Wang , Bo-Tao Jiang","doi":"10.1016/j.ejphar.2025.177676","DOIUrl":"10.1016/j.ejphar.2025.177676","url":null,"abstract":"<div><div>Renal ischemia/reperfusion (I/R) injury is the most common cause of acute kidney injury (AKI). It can progress to chronic injury and subsequently to chronic kidney disease (CKD) via the renal fibrosis pathway. Luteolin is one of the most commonly occurring flavonoids and exhibits potential therapeutic activity against various pathophysiological processes. In this study, we investigated the protective role of luteolin in counteracting renal I/R injury and its potential mechanisms through systematic network pharmacology, molecular docking, and in vivo experimental studies. Using network pharmacology, we constructed and analyzed a luteolin-renal I/R injury target network. We assessed the relationship between luteolin and renal I/R injury targets using molecular docking analysis. Subsequently, we established a rat model of AKI to CKD transition using unilateral ischemia/reperfusion injury (UIRI), and detected changes in the expression of related proteins using biochemical indices.</div><div>Network pharmacological analysis and molecular docking showed that luteolin affected renal I/R injury through multiple targets and pathways. As demonstrated by in vivo experiments, luteolin significantly attenuated renal I/R-induced oxidative injury by inhibiting renal lipid peroxidation in rats through the modulation of the nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) pathway. Luteolin attenuated the levels of relevant inflammatory markers, significantly upregulated the synthesis of apoptosis-related proteins, and downregulated the expression of anti-apoptotic proteins. Our results suggest that luteolin effectively inhibited oxidative damage, inflammation, apoptosis, and fibrosis caused by renal I/R injury, thus exerting a nephroprotective effect. The antioxidant effects of luteolin may be related to the regulation of Nrf2/HO-1 signaling.</div></div>","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":"999 ","pages":"Article 177676"},"PeriodicalIF":4.2,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143891647","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

Glucose-dependent insulinotropic peptide and beyond: co-agonist innovations in the treatment of metabolic diseases 葡萄糖依赖性胰岛素肽及其他：代谢性疾病治疗的协同激动剂创新

IF 4.2 3区医学

European journal of pharmacology Pub Date : 2025-04-28 DOI: 10.1016/j.ejphar.2025.177681

Chenxu Zhou , Binbin Gong , Xiyu Liu , Guoqiang Hu , Lidan Sun

{"title":"Glucose-dependent insulinotropic peptide and beyond: co-agonist innovations in the treatment of metabolic diseases","authors":"Chenxu Zhou , Binbin Gong , Xiyu Liu , Guoqiang Hu , Lidan Sun","doi":"10.1016/j.ejphar.2025.177681","DOIUrl":"10.1016/j.ejphar.2025.177681","url":null,"abstract":"<div><div>Glucose-dependent insulinotropic peptide (GIP), a key incretin hormone, has emerged as a pivotal therapeutic target in metabolic disorders. Historically, its therapeutic potential in type 2 diabetes mellitus (T2DM) has been underestimated owing to GIP resistance and its limited acute effects on glycemic control and body weight regulation. However, emerging evidence has demonstrated that GIP resistance is reversible through sustained glycemic improvement, thereby restoring its physiological effectiveness. With the development of gut hormone co-agonists, the potential of GIP in the treatment of metabolic diseases has been reevaluated. The study of GIP and its co-agonists such as glucagon-like peptide-1 (GLP-1), revealed that its mechanism of action in regulating blood glucose, fat metabolism, and bone metabolism is complex and diverse. A better understanding of GIP evolution can help in designing more effective GIP-based treatment strategies. In this review, we summarize the physiological functions of GIP, systematically explores its diverse structural modifications, delves into the realm of unimolecular multi-agonists, and provides a nuanced portrayal of the developmental prospects of GIP analogs.</div></div>","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":"999 ","pages":"Article 177681"},"PeriodicalIF":4.2,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143899821","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

Amiodarone oral subacute treatment prevents cardiac dysfunction of ischemia/reperfusion in rats: Mechanisms and influence of hypothyroidism 胺碘酮口服亚急性治疗预防大鼠缺血/再灌注心功能障碍：甲状腺功能减退的机制及影响

IF 4.2 3区医学

European journal of pharmacology Pub Date : 2025-04-26 DOI: 10.1016/j.ejphar.2025.177677

Matías Bayley , María Inés Ragone , Romina G. Díaz , Alicia E. Consolini

{"title":"Amiodarone oral subacute treatment prevents cardiac dysfunction of ischemia/reperfusion in rats: Mechanisms and influence of hypothyroidism","authors":"Matías Bayley , María Inés Ragone , Romina G. Díaz , Alicia E. Consolini","doi":"10.1016/j.ejphar.2025.177677","DOIUrl":"10.1016/j.ejphar.2025.177677","url":null,"abstract":"<div><div>The antiarrhythmic amiodarone is frequently used, but it induces a risk of hypothyroidism. Their effects on myocardial function after ischemia are unclear. The aim of this work was to evaluate the effects on cardiac recovery during ischemia and reperfusion (I/R) of a subacute oral treatment with amiodarone on rats, and the influence of hypothyroidism, as well as the underlying mechanisms. Hypothyroid rat model (HypoT) was obtained by oral intake of 0.02 % methimazole for 15 days. Amiodarone treatment (30 mg/kg/day) was administered in both HypoT and euthyroid (EuT) rats during a week. Isolated hearts were perfused inside a flow-calorimeter to measure contractile performance (P), total heat rate (Ht) and muscle economy (P/Ht). Hearts were exposed to 30 min I and 45 min R. Moreover, infarct size and western-blot were determined at the end of R. Amiodarone improved the postischemic recovery in EuT rat hearts but reduced it in HypoT rat hearts. By using several selective pharmacological tools, it was demonstrated that amiodarone cardioprotection in EuT rats was strongly reduced by blocking PI3K/AKT, PKC, iNOS and mitochondrial ATP-dependent K<sup>+</sup> channels (mK<sub>ATP</sub>). Moreover, the reduced postischemic recovery in HypoT hearts treated with amiodarone was reversed by perfusing a scavenger of oxygen reactive species. Results suggest that protective effects of amiodarone in EuT rat hearts involved a pathway with scavenging of hydroxyl radicals and activation of iNOS, PKC, PI3K/AKT and mK<sub>ATP</sub> channels. However, ROS production was increased in hearts of HypoT rats treated with amiodarone, causing the reduced post-ischemic mechano-energetic recovery.</div></div>","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":"999 ","pages":"Article 177677"},"PeriodicalIF":4.2,"publicationDate":"2025-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143882786","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

Kumatakenin alleviates depressive-like behaviors by suppressing excessive autophagy in hippocampus via ATG5 Kumatakenin通过ATG5抑制海马过度自噬来缓解抑郁样行为

IF 4.2 3区医学

European journal of pharmacology Pub Date : 2025-04-26 DOI: 10.1016/j.ejphar.2025.177688

Lei Li , Ling Gu , Yang Hua , Huiying Xu , Yuyan Ling , Lijun Tong , Meijuan Chen , Ruiting Ma

{"title":"Kumatakenin alleviates depressive-like behaviors by suppressing excessive autophagy in hippocampus via ATG5","authors":"Lei Li , Ling Gu , Yang Hua , Huiying Xu , Yuyan Ling , Lijun Tong , Meijuan Chen , Ruiting Ma","doi":"10.1016/j.ejphar.2025.177688","DOIUrl":"10.1016/j.ejphar.2025.177688","url":null,"abstract":"<div><div>The prevalence of depression has been escalating annually, imposing a substantial burden on both individuals and society. Radix Astragali, a multifaceted herb utilized in traditional Chinese medicine, has been employed in clinical settings for the treatment of depression. Kumatakenin, a principal active constituent of Radix Astragali, has yet to be thoroughly investigated for its potential antidepressant effects. In this study, we elucidated a novel effect of Kumatakenin, which ameliorated depression-like behaviors by modulating excessive autophagy in the hippocampus of mice exhibiting depressive symptoms. Utilizing transmission electron microscopy, we identified a significant increase in autophagosomes within the hippocampal region of depressed mice, which was notably reduced following Kumatakenin administration. Further, molecular docking analyses revealed an interaction between Kumatakenin and autophagy-related gene 5 (ATG5). At the protein level, Kumatakenin administration resulted in a marked decrease in microtubule-associated protein 1 light chain 3 (LC3) and ATG5 levels within hippocampal tissues. At the cellular level, in a corticosterone (CORT)-induced cell model, Kumatakenin significantly diminished the levels of LC3 and ATG5. Upon overexpression of ATG5 through lentiviral transfection, the ability of Kumatakenin to reduce LC3 and ATG5 levels was nullified. These observations suggested that Kumatakenin exerted its antidepressant effects by decreasing LC3 and ATG5 concentrations in hippocampal tissues.</div></div>","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":"999 ","pages":"Article 177688"},"PeriodicalIF":4.2,"publicationDate":"2025-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143891643","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