European journal of pharmacology最新文献

{"title":"Small interfering RNA (siRNA) based therapies for cancer treatment: A special focus on cervical cancer","authors":"Labdhi Bavishi,&nbsp;Shital B. Butani,&nbsp;Snehal S. Patel","doi":"10.1016/j.ejphar.2025.178198","DOIUrl":"10.1016/j.ejphar.2025.178198","url":null,"abstract":"<div><div>Small interfering RNA (siRNA)-based therapies are rapidly advancing as a novel approach in cancer treatment by selectively silencing oncogenes and disease-associated genes via the RNA interference (RNAi) pathway. By harnessing the body's natural cellular machinery to degrade specific messenger RNA (mRNAs), siRNA therapies prevent the production of harmful proteins with remarkable precision, offering reduced off-target effects compared to conventional chemotherapy or radiation. This review emphasizes the growing importance of siRNA in various cancers, particularly cervical cancer, which is often linked to persistent Human Papillomavirus (HPV) infections. It discusses how siRNA therapies target key viral oncogenes like E6 and E7, reactivating tumour suppressor pathways, modulating immune responses and improving sensitivity to chemotherapy. In addition, the review explores recent advancements in siRNA delivery strategies such as lipid nanoparticles, polymeric carriers, dendrimers and exosomes that address major challenges like nuclease degradation, limited cellular uptake and immune activation. The clinical potential of siRNA, including its integration with personalized medicine and ongoing clinical trials, is evaluated, alongside a critical analysis of current limitations such as immunogenicity, delivery efficiency and manufacturing complexities. Altogether, the review highlights both the promises and challenges of siRNA-based therapies and points towards future directions needed to realize their full clinical potential in oncology.</div></div>","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":"1007 ","pages":"Article 178198"},"PeriodicalIF":4.7,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145185087","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}

{"title":"Remimazolam alleviates intracerebral hemorrhage outcomes by suppressing neuronal ferroptosis","authors":"Xin Li ,&nbsp;Chunlei Xing ,&nbsp;Mi Tian ,&nbsp;Biying Liu ,&nbsp;Jiayu Tong ,&nbsp;Haonan Yu ,&nbsp;Chengya Huang ,&nbsp;Li Su ,&nbsp;Xingji You ,&nbsp;Jingxiang Wu","doi":"10.1016/j.ejphar.2025.178203","DOIUrl":"10.1016/j.ejphar.2025.178203","url":null,"abstract":"<div><div>Intracerebral hemorrhage (ICH) is a severe stroke subtype associated with high morbidity and mortality. Secondary brain injury after ICH involves complex pathological mechanisms, including neuronal apoptosis, neuroinflammation, and oxidative stress, yet effective therapeutic interventions remain limited. Remimazolam, an ultra-short-acting sedative anesthetic, has emerged as a promising candidate due to its reported neuroprotective and anti-inflammatory effects. However, its precise role in ICH pathogenesis remains unclear. Using a murine ICH model, we found that remimazolam treatment significantly improved neurological function, reduced cerebral edema, and attenuated neuronal apoptosis. Given the critical role of ferroptosis in ICH-induced brain injury, we further investigated its involvement. Mechanistic investigations revealed that remimazolam significantly reduced the accumulation of ROS and Fe²⁺ in both perihematomal regions of ICH mice and HT22 cells treated with hemin. These findings highlight remimazolam's potential to inhibit ferroptosis and improve cognitive function in ICH, offering a promising therapeutic strategy for ICH.</div></div>","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":"1006 ","pages":"Article 178203"},"PeriodicalIF":4.7,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145181960","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}

{"title":"Mapping the evolving landscape of lecanemab research in Alzheimer's Disease: A bibliometric analysis","authors":"Xu Zhao ,&nbsp;Ruijia Ma ,&nbsp;Jiaxing Shen ,&nbsp;Dingwen Xu ,&nbsp;Zhe Yang","doi":"10.1016/j.ejphar.2025.178187","DOIUrl":"10.1016/j.ejphar.2025.178187","url":null,"abstract":"<div><h3>Background</h3><div>Lecanemab, a monoclonal antibody that targets amyloid-beta aggregates, has emerged as a promising therapeutic for Alzheimer's disease (AD). AD is a progressive neurodegenerative disorder characterized by cognitive decline and amyloid pathology. Research on the use of lecanemab in treating AD has increased; however, no relevant bibliometric analyses have been conducted. To address this gap, this study employed bibliometric methods to search for the relevant literature and analyze research trends investigating AD and lecanemab.</div></div><div><h3>Methods</h3><div>We performed a literature search of the Web of Science core database for studies investigating AD and lecanemab, published from database inception up to April 3rd, 2025. After rigorous screening, Excel, VOSviewer, and CiteSpace were used to perform a bibliometric analysis of publications, citations, and collaboration networks among countries, institutions, and authors, along with cluster and burst analyses of keywords. Coremine was used for text mining entries significantly related to AD and lecanemab.</div></div><div><h3>Results</h3><div>The number of studies published on AD and lecanemab has increased annually. The countries with the highest publication output were the United States, the United Kingdom, and China. The leading institutions that produced the most articles were Eisai Inc. (Bunkyo City, Tokyo, Japan), Uppsala University (Uppsala, Sweden), and Harvard Medical School (Boston, MA, USA). The top three authors were Lars Lannfelt, Shobha Dhadda, and Michio Kanekiyo. The most prolific journals included <em>The Journal of Alzheimer's Disease</em>, <em>Alzheimer's and Dementia,</em> and <em>Ageing Research Reviews</em>. The most cited article was “Lecanemab in Early Alzheimer's Disease,” by Van Dyck et al., published in <em>The New England Journal of Medicine</em> in 2023, which has accrued 172 citations. The 10 most frequently occurring keywords were Alzheimer's disease, lecanemab, dementia, aducanumab, amyloid-beta, immunotherapy, tau, a-beta, mouse model, and donanemab. Text mining revealed that drugs, anatomical structures, chemical molecules, genes, diseases, and procedures were significantly associated with both AD and lecanemab.</div></div><div><h3>Conclusion</h3><div>The bibliometric and text mining analysis revealed trends in research investigating the correlation between lecanemab and AD. It analyzed the cooperation among countries, regions, and authors, highlighting recent research hotspots. These data offer objective insights for scientific research and clinical practice on lecanemab and AD. These findings provide a roadmap for prioritizing clinical trials, optimizing drug development strategies, and addressing knowledge gaps in amyloid-targeted therapies.</div></div>","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":"1006 ","pages":"Article 178187"},"PeriodicalIF":4.7,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145185067","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}

{"title":"Protective effects of acemannan-enriched Aloe polysaccharide J2 against UVA-induced autophagic cell death in retinal pigment epithelial cells","authors":"Chen-Chun Kao ,&nbsp;Uvarani Chokkalingam ,&nbsp;Anuma Singh ,&nbsp;Pei-Chun Shih ,&nbsp;Ekambaranellore Prakash ,&nbsp;Jang-Shiun Wang","doi":"10.1016/j.ejphar.2025.178199","DOIUrl":"10.1016/j.ejphar.2025.178199","url":null,"abstract":"<div><div>Age-Related Macular Degeneration (AMD) is one of the leading causes of irreversible vision loss worldwide, characterized by the degeneration of the retinal pigment epithelium (RPE) and photoreceptor cells, resulting in progressive loss of central vision. RPE cells are highly specialized and essential for retinal function, and their malfunction due to genetic, environmental, or age-related factors contributes significantly to AMD pathogenesis. Ultraviolet A (UVA) radiation is recognized as a major causative factor, as it induces the accumulation of reactive oxygen species (ROS) in RPE cells, ultimately contributing to the development of AMD. On the other hand, acemannan, a D-isomer mucopolysaccharide derived from <em>Aloe vera</em> pulp, is known for its antioxidant and anti-inflammatory properties. In this study, we extracted a highly purified Aloe-derived polysaccharide fraction enriched in acemannan, designated Aloe polysaccharide J2 (ACJ2), to investigate its protective effects against UVA-induced RPE damage. The results showed that post-treatment with ACJ2 significantly reduced UVA-induced cell death by lowering mitochondrial ROS levels, suppressing phosphorylation of mitogen-activated protein kinases (MAPKs), including p38 MAPK, extracellular signal-regulated kinase 1/2 (ERK1/2), and c-Jun N-terminal kinase (JNK), and downregulating proinflammatory mediators including tumor necrosis factor alpha (TNF-α), interleukin-1 beta (IL-1β), and inducible nitric oxide synthase (iNOS). Furthermore, ACJ2 enhanced heme oxygenase-1 (HO-1) expression and mitochondrial DNA levels, and inhibited p62/sequestosome-1 (p62) consumption and microtubule-associated protein 1 light chain 3 (LC3)-I/II conversion, thereby reducing autophagic flux. These findings demonstrate that ACJ2 mitigates UVA-induced damage and restores disrupted autophagy in RPE cells, supporting its potential as a therapeutic candidate for AMD.</div></div>","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":"1006 ","pages":"Article 178199"},"PeriodicalIF":4.7,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145185104","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}

{"title":"Early Sacubitril/valsartan Therapy Reduces Ventricular Remodeling and Cardiac Events in Patients with Acute Anterior Myocardial Infarction.","authors":"Suling Ye, Nina Guo, Jie Li, Jinglin Zhao, Dafei Zong, Lili Wang","doi":"10.1016/j.ejphar.2025.178188","DOIUrl":"https://doi.org/10.1016/j.ejphar.2025.178188","url":null,"abstract":"<p><strong>Purpose: </strong>To compare the effects of early angiotensin receptor-neprilysin inhibitor (ARNI) versus angiotensin-converting enzyme inhibitor or angiotensin receptor blocker (ACEI/ARB) therapy on left ventricular remodeling and heart failure progression in patients with acute anterior wall myocardial infarction.</p><p><strong>Methods: </strong>Patients were stratified by treatment into ARNI (n=97) and ACEI/ARB (n=71) groups. Baseline characteristics, cardiac ultrasound data (baseline, 0-3 months, 6-12 months), and major adverse cardiac events (MACEs) were analyzed.</p><p><strong>Results: </strong>The ARNI group demonstrated significantly greater improvements in left ventricular end-diastolic diameter and relative wall thickness versus the ACEI/ARB group. Subgroup analyses (target-dose achievers, emergency reperfusion recipients, left ventricular ejection fraction ≥50% patients) consistently showed better improvements with ARNI. ARNI therapy also significantly reduced MACEs risk (HR = 0.392, 95% CI: 0.194-0.791, P = 0.009).</p><p><strong>Conclusion: </strong>Compared with ACEI/ARB, ARNI demonstrated enhanced preservation of cardiac function, attenuation of adverse ventricular remodeling, and maintenance of ventricular geometry following myocardial infarction. Additionally, ARNI was associated with a reduction in major adverse cardiac events and improved survival outcomes.</p>","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":" ","pages":"178188"},"PeriodicalIF":4.7,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145185062","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}

{"title":"Varenicline as a cardioprotective agent against doxorubicin-induced toxicity: A study on apoptotic, TLR4/NF-κB, and inflammasome/caspase-1/IL-1β pathway modulation in a rat model","authors":"Naglaa M. Badr ,&nbsp;Mahmoud E. Youssef ,&nbsp;Ahmed A. Shaaban ,&nbsp;Hassan El-Kashef","doi":"10.1016/j.ejphar.2025.178200","DOIUrl":"10.1016/j.ejphar.2025.178200","url":null,"abstract":"<div><div>Doxorubicin-induced cardiotoxicity represents a significant challenge in oncology, impacting treatment efficacy and patient quality of life. The search for cardioprotective agents that preserve anticancer efficacy remains ongoing. Varenicline, a prescription medication commonly used to treat smoking addiction, showed promising outcomes in modulating inflammatory responses, indicating a potential protective role against doxorubicin-induced cardiac injury. This study investigates varenicline's cardioprotective effects on doxorubicin-induced cardiotoxicity, focusing on inflammatory and apoptotic signaling pathways.</div><div>In this study, rats were divided into five experimental groups: control (Saline), a varenicline-only group (100 μg/kg/day), a doxorubicin-only group (2.5 mg/kg every 48 h for eight doses), and two combination groups receiving doxorubicin with either a high (100 μg/kg/day) or low (50 μg/kg/day) dose of varenicline, over 18 days.</div><div>ECG analysis indicated that doxorubicin treatment caused significant disruptions, including ST-segment elevation and prolonged QT intervals, along with elevated levels of cTnT and CK-MB, signifying cardiac injury. Doxorubicin treatment also significantly increased pro-inflammatory and apoptotic markers such as TLR4, Bax, TNF-α, NF-κB, TRAF-6, IL-1β, and IL-6, while activating inflammasome components like NLRP3 and elevating the Bax/Bcl-2 ratio and caspase-3 activity along with decreasing the expression of α7-nAchR. In contrast, varenicline co-treatment improved ECG parameters, reduced TLR4 and NF-κB levels, attenuated pro-apoptotic markers, and increased α7-nAchR expression, highlighting its potential as a therapeutic agent for mitigating doxorubicin-induced cardiotoxicity.</div><div>In conclusion, varenicline demonstrates protective effects by modulating inflammatory and apoptotic pathways, improving cardiac function and electrical stability. Therefore, we suggest that varenicline may be a potential therapeutic agent for mitigating doxorubicin-induced cardiotoxicity.</div></div>","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":"1006 ","pages":"Article 178200"},"PeriodicalIF":4.7,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145185065","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}

{"title":"Sirtuin 6-driven ASC deacetylation confers hepatoprotection: A promising approach to inflammasome inhibition in experimental NASH","authors":"Rabab S. Hamad ,&nbsp;Waseem Ali Hasan ,&nbsp;Elsayed A. Elmorsy ,&nbsp;Alshaimaa A. Farrag ,&nbsp;Mahmoud A. Abdelaziz ,&nbsp;Adel I. Alalawy ,&nbsp;Alaa Muqbil Alsirhani ,&nbsp;Munerah M. Al Dawsari ,&nbsp;Attalla F. El-kott ,&nbsp;Mohammed A. AlShehri ,&nbsp;Sally Negm ,&nbsp;Mohamed A.M. Ali ,&nbsp;Mohamed A.S. Abd Elzaher ,&nbsp;Amira Karam khalifa ,&nbsp;Ahmed Gaafar ,&nbsp;Sameh Saber","doi":"10.1016/j.ejphar.2025.178202","DOIUrl":"10.1016/j.ejphar.2025.178202","url":null,"abstract":"<div><div>Nonalcoholic steatohepatitis (NASH), a progressive subtype of metabolic-associated steatotic liver disease (MASLD), is characterized by hepatocellular injury, inflammation, oxidative stress, and fibrosis. Sirtuin 6 (SIRT6), a deacetylase, plays a crucial role in regulating hepatic metabolic and inflammatory pathways. This work assessed the therapeutic potential and underlying mechanism of MDL811, a selective SIRT6 activator, in a rat model of NASH induced by diethylnitrosamine, high-fat diet, and thioacetamide. Rats were treated with MDL811 alone or in combination with the SIRT6 inhibitor SIRT6-IN-1. MDL811 significantly improved liver function markers, lipid profile, and antioxidant enzyme activity, while reducing hepatic steatosis, inflammation, and fibrosis. Mechanistically, MDL811 enhanced hepatic SIRT6 activity and exerted anti-inflammatory effects by reducing acetylation of the inflammasome adaptor ASC, suppressing NLRP3 inflammasome activation, and decreasing nuclear NFκB p65 activity and downstream cytokine expression. In parallel, MDL811 attenuated fibrosis by inhibiting SMAD2/3 phosphorylation and downregulating fibrotic markers such as α-SMA, TGF-β1, and TIMP-1, while restoring PPARα expression. Co-treatment with SIRT6-IN-1 abolished the beneficial effects of MDL811 on inflammation, fibrosis, oxidative stress, and lipid metabolism, confirming the central role of SIRT6 activation. Notably, SIRT6-IN-1 alone reduced hepatic SIRT6 activity in control animals without inducing significant pathology, but selectively worsened inflammatory and fibrogenic pathways in the NASH context. These findings show that MDL811 protects against NASH through SIRT6-dependent inhibition of inflammasome signaling, with ASC deacetylation identified as a key mechanism. Modulating the SIRT6–ASC axis may therefore represent a promising strategy for managing inflammation-driven diseases such as NASH.</div></div>","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":"1006 ","pages":"Article 178202"},"PeriodicalIF":4.7,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145185092","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}

{"title":"Exploring Anticholinergic and anti-amnesic potential of methyl substituted monocarbonyl curcumin derivatives","authors":"Muhammad Bilal Afridi ,&nbsp;Syed Wadood Ali Shah ,&nbsp;Haya Hussain ,&nbsp;Ahmed A. Elhenawy ,&nbsp;Muhammad Mujtaba ,&nbsp;Jamelah S. Al-Otaibi ,&nbsp;Haroon Khan","doi":"10.1016/j.ejphar.2025.178193","DOIUrl":"10.1016/j.ejphar.2025.178193","url":null,"abstract":"<div><div>Alzheimer's disease (AD) is the most prevalent form of dementia or amnesia, characterized primarily by loss of acetylcholine (ACh), due to increased activity of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), both of which accelerate ACh degradation, and exacerbate cholinergic dysfunction. In this regard, the synthetic methyl-substituted monocarbonyl curcumin derivatives (<strong>BL1-BL3</strong>) were analyzed for AChE and BChE inhibition, followed by molecular docking studies. Scopolamine (1 mg/kg) was used to induce amnesia in mice. The results of <strong>BL1-BL3</strong> demonstrated a significant inhibitory effect especially against AChE compared to BChE enzymes, with IC₅₀ of 128.4, 118.4, 170.9 μg/mL against AChE and 334.3, 1168, 288.2 μg/mL against BChE, respectively. These compounds exhibited strong binding affinities to both target proteins in docking studies. Scopolamine administration induced significant memory deficits in mice, that was significantly (<em>P</em> &lt; 0.001) mitigated by pretreatment with <strong>BL1-BL3</strong> in the Y-maze test at both 7.5 and 15 mg/kg doses by restoring spontaneous alternation performance (SAP). In the novel object recognition test (NORT), a prominent (<em>P</em> &lt; 0.001) improvement in memory retention was seen during the test phase, and enhanced the discrimination index (DI) at both tested doses. Biochemical analyses of hippocampal tissue further supported the behavioral data. Treatment with <strong>BL1-BL3</strong> effectively decreases AChE and malondialdehyde (MDA) levels while increasing catalase (CAT) and superoxide dismutase (SOD) levels. Overall, <strong>BL2</strong> was found to be most significant. In short, <strong>BL1</strong>-<strong>BL3</strong> emerged as potential therapeutic agents for AD due to significant effects <em>in vitro</em> and <em>in vivo</em> experimental models, and are also equally supported by in silico studies.</div></div>","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":"1007 ","pages":"Article 178193"},"PeriodicalIF":4.7,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145181926","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}

{"title":"The anticonvulsant activity of trace amine-associated receptor 1 (TAAR1) agonists involves GABAB receptors in mice","authors":"Misato Yoshikawa,&nbsp;Miki Fukugami,&nbsp;Katsuya Suemaru","doi":"10.1016/j.ejphar.2025.178194","DOIUrl":"10.1016/j.ejphar.2025.178194","url":null,"abstract":"<div><div>Trace amine-associated receptor 1 (TAAR1) agonists have shown potential as therapeutic agents for schizophrenia and other neuropsychiatric disorders. However, it remains unclear whether TAAR1 agonists have anticonvulsant activity. We therefore investigated the effects of TAAR1 agonists on acute seizures induced by continuous intravenous infusion of a GABA_A receptor antagonist, pentylenetetrazol (PTZ), and an inhibitor of voltage-gated potassium channels, 4-aminopyridine (4-AP), in mice. The TAAR1 agonists RO5263397 and RO5256390 did not affect the threshold dose for PTZ-induced seizures; however, they significantly increased the threshold for 4-AP-induced seizures. The anticonvulsant activities of these TAAR1 agonists were blocked by intracerebroventricular administration of CGP 35348, a GABA_B receptor antagonist. These results suggest that GABA_B receptors are involved in the anticonvulsant effects of TAAR1 agonists.</div></div>","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":"1006 ","pages":"Article 178194"},"PeriodicalIF":4.7,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145181924","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}

{"title":"Protective efficacy and mechanism of gypenosides against diabetic cataracts via the ferroptosis pathway: A study based on network pharmacology.","authors":"Anqi Pei, Ying Ma, Mingjun Gao, Qi Zhao","doi":"10.1016/j.ejphar.2025.178175","DOIUrl":"https://doi.org/10.1016/j.ejphar.2025.178175","url":null,"abstract":"<p><p>Gypenosides (GPs), extracted from the traditional Chinese herb Gynostemma pentaphyllum (Thunb.) Makino, have exhibited a wide range of pharmacological effects, including anticancer, anti-obesity, lipid-improving, anti-inflammatory, and neuroprotective properties, in addition to being used in treating diabetes mellitus and lipid metabolism disorder. Although these pharmacological properties suggest the potential for diabetic cataracts (DC) treatment, it is unclear whether Gynostemma has protective effects against DC and the possible mechanisms involved. Previous studies have confirmed the respective relations between ferroptosis and diabetes mellitus,diabetic complications. To investigate the protective effects of GPs on DC from the perspective of ferroptosis, and to explore the potential regulatory pathways and mechanisms. A diabetic rat model was established and treated with GPs. PPI network were constructed to obtain the hub targets. The biological functions and potential pathways were analyzed through GO and KEGG enrichment. Molecular docking, ELISA was used to verify the interactions between Gynostemma and the key targets and the reliability of the targets. HE staining was performed to observe the pathomorphological alterations. The kit, IHC and western blot was performed to evaluate the expression of MDA,SOD,GSH, total iron content, ICAM-1,and the ferroptosis-related proteins of SLC7A11/GPX4/P53 signaling pathway in the lens tissue. The study highlighted the effects of Gynostemma in reducing crystalline pathomorphological changes and mitigating ferroptosis in diabetic cataracts. It further suggested that these protective effects may be achieved through the regulation of the ferroptosis-related P53/SLC7A11/GPX4 pathway.</p>","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":" ","pages":"178175"},"PeriodicalIF":4.7,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145174143","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}