European journal of pharmacology最新文献

{"title":"Icariside II ameliorates slow transit constipation by inhibiting macrophage polarization and suppressing the cGAS-STING pathway","authors":"Ziying Jiang ,&nbsp;Fangxu Yin ,&nbsp;Yaqian Ping ,&nbsp;Wenyue Ma,&nbsp;Xiaohui Dou,&nbsp;Rui Li,&nbsp;Kai Zheng,&nbsp;Yunbin Tong,&nbsp;Lu Han,&nbsp;Lang Fu,&nbsp;Bozhao Wu,&nbsp;Daqing Sun","doi":"10.1016/j.ejphar.2025.178166","DOIUrl":"10.1016/j.ejphar.2025.178166","url":null,"abstract":"<div><h3>Background</h3><div>Slow transit constipation (STC) is a functional disorder characterized by slowed colonic peristalsis and delayed emptying. Its pathogenesis involves enteric nervous system damage and immune dysregulation, among other factors. Icariside II (ICS II) is a natural flavonoid glycoside from <em>Herba Epimedii</em> and is known for its anti-inflammatory, antioxidant, and neuroprotective effects. However, the effect of ICS II on STC and the underlying mechanisms remains unclear.</div></div><div><h3>Methods</h3><div>In this study, the effects of ICS II on STC were assessed in a loperamide-induced STC animal model. Drug efficacy was evaluated by observing the general phenotype using hematoxylin and eosin staining, immunofluorescence, Western blotting, and flow cytometry. Additionally, the roles of intestinal macrophages and the cyclic guanosine monophosphate-adenosine synthase/stimulator of interferon genes (cGAS-STING) signaling pathway in STC were studied using clodronate liposomes and STING inhibitor.</div></div><div><h3>Results</h3><div>ICS II treatment significantly increased fecal count, fecal moisture content, and intestinal propulsion rate, shortened first dark fecal defecation time, and improved colonic histopathology in the STC animal model. Notably, ICS II reduced intestinal M1-type macrophage proportion, downregulated proteins in the cGAS-STING signaling pathway, and lowered the release of inflammatory factors interleukin (IL)-1β, IL-6, and tumor necrosis factor-α. ICS II also decreased intestinal neuronal damage and increased nerve fiber density in STC disease, demonstrating its anti-inflammatory and neuroprotective effects.</div></div><div><h3>Conclusion</h3><div>This study provides evidence that ICS II exerts significant anti-inflammatory and neuroprotective effects. This is achieved by inhibiting the cGAS-STING pathway and suppressing macrophage M1 polarization, suggesting its potential as a therapeutic agent for STC.</div></div>","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":"1006 ","pages":"Article 178166"},"PeriodicalIF":4.7,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145085560","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":"Modulating monoaminergic systems: A study on 3,5-dimethyl-1-phenyl-4-(phenylselenyl)-1H-pyrazole in lipopolysaccharide-induced depressive-like symptoms in mice","authors":"Giuliana P. Zugno ,&nbsp;Paloma T. Birmann ,&nbsp;Airton Sinott ,&nbsp;Jenifer Fetter ,&nbsp;Renata L. de Oliveira ,&nbsp;Livia C.L. Valente ,&nbsp;Daniela Hartwig ,&nbsp;Lucielli Savegnago","doi":"10.1016/j.ejphar.2025.178176","DOIUrl":"10.1016/j.ejphar.2025.178176","url":null,"abstract":"<div><div>This study investigated 3,5-dimethyl-1-phenyl-4-(phenylselenyl)-1H-pyrazole (SePy) antidepressant-like potential using <em>in vivo</em>, <em>ex vivo</em>, and <em>in silico</em> approaches and evaluated its hepatic and renal safety profile. Male Swiss mice received lipopolysaccharide (LPS 0.83 mg/kg, intraperitoneally) and were treated with SePy (10 mg/kg, i.g.) 24 h later. Antidepressant-like activity was evaluated using the tail suspension test (TST) and forced swimming test (FST). Monoamine oxidase (MAO) activity was subsequently measured in the prefrontal cortex, hippocampi, and small intestine to investigate previously unexplored mechanistic pathways. SePy significantly reduced immobility time in both tests (TST and FST) and inhibited MAO-A and MAO-B activities in all regions analyzed. <em>In silico</em> docking indicated high affinity of SePy for catalytic residues of both MAO isoforms, comparable to the reference inhibitor isocarboxazide. Toxicological analysis of SePy (5–300 mg/kg) in female mice revealed no significant hepatic alterations (alanine and aspartate aminotransferase), although elevated urea and creatinine levels suggest possible renal effects at higher doses. Taken together, the results suggest that SePy may exert antidepressant-like effects via monoaminergic modulation and displays a favorable hepatic safety profile. Additional studies are warranted to confirm its renal safety and further explore its pharmacological potential under inflammatory conditions.</div></div>","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":"1006 ","pages":"Article 178176"},"PeriodicalIF":4.7,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145085510","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":"Betulinic acid attenuates lipopolysaccharide-induced cardiac injury by promoting mitophagy with enhancing PINK1/Parkin and suppressing BNIP3","authors":"Xin-Ru Zhou ,&nbsp;Xiang-Fei Meng ,&nbsp;Yu-Xiao Zhang ,&nbsp;Zi-Yan Zhang ,&nbsp;Chun-Yan Jiang ,&nbsp;Yu-Peng Han ,&nbsp;Jin-Ting Yang ,&nbsp;Ling-Bo Qian","doi":"10.1016/j.ejphar.2025.178169","DOIUrl":"10.1016/j.ejphar.2025.178169","url":null,"abstract":"<div><div>Betulinic acid (BA), a natural pentacyclic triterpene, has been shown to promote autophagy and attenuate sepsis-induced organ injury, yet its role in mitophagy-mediated cardioprotection remains unclear. Here, we evaluated the effects of oral BA treatment (25 mg/kg, 5 days) on lipopolysaccharide (LPS)-induced cardiac injury in male Sprague-Dawley rats. BA significantly improved cardiac function, reduced myocardial injury markers (cardiac troponin I, creatine kinase-MB), and suppressed inflammatory (tumor necrosis factor-α, interleukin-1β, myeloperoxidase activity) and oxidative responses in LPS-induced sepsis. Moreover, BA improved cardiac mitochondrial function by enhancing respiratory chain complex activity and ATP synthesis while limiting the opening of mitochondrial permeability transition pore and loss of mitochondrial membrane potential in LPS-challenged rats. Western blot and immunofluorescence analyses showed that BA enhanced PTEN-induced putative kinase 1 (PINK1)/Parkin-initiated mitophagy and suppressed BNIP3 (Bcl-2/adenovirus E1B 19 kDa interacting protein 3) expression in LPS-challenged rat hearts. Importantly, these cardioprotective effects of BA were abrogated by the mitophagy inhibitor Mdivi-1. Collectively, these results indicate that BA alleviates cardiac injury in LPS-induced sepsis by upregulating PINK1/Parkin to facilitate mitophagy and suppressing BNIP3 signaling.</div></div>","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":"1006 ","pages":"Article 178169"},"PeriodicalIF":4.7,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145085501","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":"Erianin induces apoptosis of thyroid cancer cells via TNF signaling pathway","authors":"Nailin Gao ,&nbsp;Jihua Han ,&nbsp;Xiang Sun ,&nbsp;Ju Yu ,&nbsp;Jiayong Huang ,&nbsp;Rengyun Liu ,&nbsp;Yan-Lai Tang ,&nbsp;Chunlei Nie","doi":"10.1016/j.ejphar.2025.178167","DOIUrl":"10.1016/j.ejphar.2025.178167","url":null,"abstract":"<div><div>Thyroid cancer is the most common endocrine malignancy, with a rising incidence rate over the past three decades. Although most thyroid cancers are indolent, clinical management of advanced thyroid cancer is still a challenge. Recent studies identified erianin as a potential anti-tumor drug in several cancer types; however, whether and how erianin against thyroid cancer remains elusive. In this study we showed that erianin significantly inhibited cell viability and colony formation of thyroid cancer cells in a genetic mutation -independent manner, and treatment thyroid cancer cells with erianin induced remarkable G2/M phase cell cycle arrest and apoptosis. By performing RNA-sequencing, we identified that TNF signaling pathway was activated by erianin in thyroid cancer cells. Moreover, the cell growth inhibitory effect of erianin was confirmed in a thyroid cancer xenograft mice model. These data suggest that erianin induces apoptosis of thyroid cancer cells by activating the TNF pathway, and the finding of the anti-tumor effect of erianin indicated a new potential therapeutic strategy for advanced thyroid cancer.</div></div>","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":"1006 ","pages":"Article 178167"},"PeriodicalIF":4.7,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145085506","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":"KN060-a humanized dual-domain antibody simultaneously targeting FXI-A2/A3 epitopes: Pioneering the anti-coagulation factor XI strategy for Aterial hypertension – Evidence from preclinical models","authors":"Xiaoyan Yu ,&nbsp;Qian Li ,&nbsp;Doudou Zhang ,&nbsp;Kangping Guo ,&nbsp;Wei Sun ,&nbsp;Wenqiao Huang ,&nbsp;Li Gao ,&nbsp;Rongmei Yan ,&nbsp;Lihong Yun ,&nbsp;Jun Wan ,&nbsp;Ting Xu ,&nbsp;Pilin Wang","doi":"10.1016/j.ejphar.2025.178171","DOIUrl":"10.1016/j.ejphar.2025.178171","url":null,"abstract":"<div><div>Growing evidence positions Factor XI (FXI) as a promising anticoagulation target, where its role in pathological thrombus formation significantly outweighs its contribution to physiological hemostasis. This distinctive pathophysiological profile has propelled FXI inhibition as a transformative therapeutic paradigm, with multiple candidates in Phase I-III trials spanning venous thromboembolism prophylaxis to arterial thrombosis prevention. Building on emerging insights into FXI-mediated vascular inflammation and remodeling, we herein unveil the first preclinical evidence supporting KN060—a humanized dual-domain antibody simultaneously targeting FXI-A2/A3 epitopes—as a novel antihypertensive agent. In angiotensin II-challenged mice, 5-week KN060 monotherapy (10 mg/kg triweekly) elicited sustained systolic blood pressure (SBP) reduction of 27.8 mmHg (120.7 mmHg in KN060 group vs 148.5 mmHg in vehicle control group). Furthermore, in spontaneously hypertensive rats, 9-week KN060 monotherapy (15 mg/kg twice weekly) achieved sustained SBP reduction of 34.7 mmHg (172.2 mmHg in KN060 group vs 206.9 mmHg in vehicle control group), concomitantly reducing left ventricular mass (0.67 g vs 0.773 g) and aortic relative media thickness (28.74 vs 31.59). Notably, co-administration of KN060 (3 mg/kg) with losartan (5 mg/kg) in SHRs demonstrated synergistic efficacy, achieving greater SBP reduction than losartan monotherapy (ΔSBP: −23.7 mmHg vs −15.9 mmHg). These findings establish KN060 as a first-in-class therapeutic bridging anticoagulation and vascular protection. Its unique bispecific architecture enables near-complete FXI activity inhibition while preserving hemostatic capacity, addressing critical limitations of conventional RAAS blockers in resistant hypertension. With an ongoing Phase Ib trial in primary hypertension patients (NMPA approval No CXSL2400827), KN060 emerges as a transformative candidate for precision management of hypertension.</div></div>","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":"1006 ","pages":"Article 178171"},"PeriodicalIF":4.7,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145085508","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":"Oral anticoagulant drugs and CNS-related hematomas: a pharmacovigilance analysis from the FAERS database","authors":"Lei Wang,&nbsp;Shujuan Zhao","doi":"10.1016/j.ejphar.2025.178163","DOIUrl":"10.1016/j.ejphar.2025.178163","url":null,"abstract":"<div><h3>Objective</h3><div>Central nervous system (CNS)-related hematoma adverse events (hAEs) are serious and devastating complications in patients receiving oral anticoagulant (OAC) therapy. We aimed to analyze and characterize the risk of CNS-related hAEs across different OACs.</div></div><div><h3>Methods</h3><div>We analyzed CNS-related hAEs from the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS) database. Disproportionality analysis was conducted to identify signals for each OAC. Logistic regression was used to assess mortality risk factors, while time-to-onset analysis characterized temporal patterns.</div></div><div><h3>Results</h3><div>A total of 5501 patients and 5641 CNS-related hAE reports were associated with OACs. Disproportionality analysis identified positive signals for all OACs, with warfarin showing the highest association (reporting odds ratio [ROR] = 38.31), followed by dabigatran (ROR = 22.76), rivaroxaban (ROR = 20.51), edoxaban (ROR = 16.81), and apixaban (ROR = 12.53). Subdural hematoma was the most frequently reported type (74.0 %). In multivariate analysis, age ≥75 years, weight &lt;60 kg, multiple adverse events (AEs), and concomitant antidepressant use were independent predictors of mortality. All OACs exhibited early failure-type temporal profiles, with warfarin demonstrating a significantly longer median onset time (435.5 days) compared to non-vitamin K antagonist oral anticoagulants (NOACs, 158.5–228.0 days; <em>P</em> &lt; 0.001).</div></div><div><h3>Conclusion</h3><div>OACs are associated with CNS-related hematomas, with varying risk profiles among agents. Advanced age, low body weight, multiple AEs, and concomitant antidepressant use are crucial mortality risk factors. CNS-related hAEs typically occur early during treatment. These findings provide insights for optimizing risk management and support appropriate anticoagulation when clinically indicated.</div></div>","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":"1006 ","pages":"Article 178163"},"PeriodicalIF":4.7,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145085522","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":"Lipid-lowering effect of evolocumab in hypertriglyceridemia-induced acute pancreatitis","authors":"Huimin Chen ,&nbsp;Xiaotong Li ,&nbsp;Jihong Chen ,&nbsp;Yarui Zhao ,&nbsp;Wenxiu Zhang ,&nbsp;Hongyu Li ,&nbsp;Xingshun Qi","doi":"10.1016/j.ejphar.2025.178148","DOIUrl":"10.1016/j.ejphar.2025.178148","url":null,"abstract":"<div><h3>Background</h3><div>The primary goal of treatment for hypertriglyceridemia-induced acute pancreatitis (HTG-AP) is to rapidly reduce blood triglyceride (TG) level to below 5.65 mmol/L. Evolocumab with a significant lipid-lowering effect, has been widely used for cardiovascular diseases. However, it has been rarely explored in HTG-AP.</div></div><div><h3>Methods</h3><div>HTG-AP patients, who were admitted between January 2022 and February 2024, were retrospectively reviewed. They were further divided according to the use of evolocumab. Blood TG levels before treatment were compared with those after 1–2 days, 3–4 days, and 5–7 days of treatment.</div></div><div><h3>Results</h3><div>Overall, 62 patients were included, of whom 30 (48.4 %) were in the evolocumab group and 32 (51.6 %) were in the non-evolocumab group. The median pre-treatment TG levels were not significantly different between them (22.17 mmol/L vs 16.94 mmol/L, <em>P</em> = 0.108). Blood TG levels after 1–2 days (<em>P</em> = 0.016) and 5–7 days (<em>P</em> = 0.007) were significantly higher in the evolocumab group than the non-evolocumab group. The proportion of TG &lt; 5.65 mmol/L after 1–2 days (6/24 vs 11/23, <em>P</em> = 0.104) and 3–4 days (10/19 vs 14/20, <em>P</em> = 0.265) was not significantly different between them, but that after 5–7 days (9/15 vs 19/20, <em>P</em> = 0.033) was significantly lower in the evolocumab group than the non-evolocumab group.</div></div><div><h3>Conclusion</h3><div>The addition of evolocumab to conventional lipid-lowering therapy did not produce any additional benefit in the reduction of blood TG levels in HTG-AP patients.</div></div>","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":"1006 ","pages":"Article 178148"},"PeriodicalIF":4.7,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145085540","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 cGAS-STING axis in kidney disease: mechanisms and therapeutic potential","authors":"Jing Li ,&nbsp;Xiaoqin Liu ,&nbsp;Haoyue Feng","doi":"10.1016/j.ejphar.2025.178155","DOIUrl":"10.1016/j.ejphar.2025.178155","url":null,"abstract":"<div><div>The cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) axis is a pivotal innate immune signaling pathway that detects cytoplasmic DNA and initiates immune responses. Recent studies have highlighted its critical role in the pathogenesis of various kidney diseases, including acute kidney injury, chronic kidney disease, diabetic kidney disease, lupus nephritis, and kidney cancer. Dysregulated cGAS-STING activation contributes to renal inflammation, fibrosis, and disease progression, making it a promising therapeutic target. This review explores the involvement of the cGAS-STING pathway in multiple renal disorders, emphasizing its dual roles in disease progression and immune regulation. Additionally, we discuss potential therapeutic strategies, including small-molecule inhibitors, agonists, and Traditional Chinese Medicine (TCM) formulations, that may modulate this pathway to attenuate kidney injury. Despite its therapeutic promise, the cGAS-STING axis exhibits complex and context-dependent regulation, with varying effects across different renal diseases. Further research is needed to elucidate its precise molecular mechanisms and optimize targeted interventions for clinical translation.</div></div>","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":"1006 ","pages":"Article 178155"},"PeriodicalIF":4.7,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145085552","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":"Nebivolol prevents coronary artery spasm by upregulating voltage-gated potassium channels via protein kinase A","authors":"Jinglu Yang ,&nbsp;Han Zhou ,&nbsp;Yan Wang ,&nbsp;Yu Liu ,&nbsp;Mingsheng Zhang","doi":"10.1016/j.ejphar.2025.178157","DOIUrl":"10.1016/j.ejphar.2025.178157","url":null,"abstract":"<div><div>Nebivolol (Neb) relaxes coronary arteries and increases coronary artery blood flow, but the underlying mechanisms need further elucidation. The vascular tension of rat coronary artery (RCA) was recorded with a wire myograph. Transmembrane K⁺ currents through voltage-dependent K⁺ (Kv) channels were measured with a patch clamp. Kv1.2 expressions were evaluated with immunofluorescent staining and Western blot. Neb (0.1–30 μM) evoked marked relaxation in RCAs pre-contracted with KCl or U46619. Denudation and L-NAME pretreatment weakened the relaxation by less than 20 %. Neb pretreatment depressed contractile responses of RCAs to various vasoconstrictors including 60 mM KCl, 0.3 μM U46619 and 0.1 μM Bay K8644. In the arterial smooth muscle cell (ASMC) of RCA, Neb reduced 60 mM KCl-induced elevation of intracellular Ca²⁺ ([Ca²⁺]_in)-sensitive fluorescent intensity and increased Kv currents. Incubation of RCAs with Neb increased Kv1.2 expressions in RCA ASMCs. Inhibitor study showed that Kv channel inhibitor 4-aminopyridine (4-AP, 1 mM) and protein kinase A (PKA) inhibitor H-89 (1 μM) attenuated Neb-induced RCA relaxation and Kv current increment in RCA ASMCs, while p38 MAPK inhibitor SB239063 (1 μM) had no effect. In summary, the present study demonstrated that Neb relaxed RCAs through PKA-mediated upregulation of Kv channels in RCA ASMCs.</div></div>","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":"1006 ","pages":"Article 178157"},"PeriodicalIF":4.7,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145079981","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":"Corilagin alleviates cardiac ischemia-reperfusion injury by inhibiting ferroptosis via PI3K/AKT pathway","authors":"Xinxin Li ,&nbsp;Zaixiao Tao ,&nbsp;Rong Huang ,&nbsp;Rui Zhang ,&nbsp;Zhenjun Ji ,&nbsp;Yang Xu ,&nbsp;Rui Sun ,&nbsp;Mi Wang ,&nbsp;Yongjun Li ,&nbsp;Genshan Ma","doi":"10.1016/j.ejphar.2025.178158","DOIUrl":"10.1016/j.ejphar.2025.178158","url":null,"abstract":"<div><div>Myocardial ischemia-reperfusion (I/R) injury is a significant complication post-revascularization in acute myocardial infarction, with limited effective clinical interventions. Corilagin, a natural polyphenolic compound, exhibits antioxidant and anti-inflammatory properties in various disease models. However, its effects and mechanisms in myocardial I/R injury remain unclear. This study aims to elucidate the specific mechanism by which Corilagin regulates ferroptosis through the PI3K/AKT signaling pathway, thereby laying a theoretical groundwork for the development of innovative cardioprotective agents. A myocardial I/R model was established in mice through left anterior descending (LAD) artery ligation, and Corilagin's effectiveness was assessed using echocardiography, biochemical assays, and histopathological analysis. Additionally, an in vitro H/R model with neonatal rat cardiomyocytes was employed to examine ferroptosis-related markers, oxidative stress, and mitochondrial function. Utilizing network pharmacology and molecular docking analysis, potential targets were identified and subsequently validated through pharmacological inhibition of the PI3K pathway with LY294002. The findings demonstrate that Corilagin exhibited significant cardioprotective effects against I/R injury, as evidenced by reduced myocardial injury markers, decreased infarct size, and improved cardiac function. In vitro studies revealed that Corilagin treatment enhanced cell viability, reduced ROS levels and iron content, and restored mitochondrial membrane potential. Network pharmacology and molecular docking identified PI3K as a crucial target, with subsequent activation of the PI3K/AKT pathway. Notably, PI3K inhibition abolished Corilagin's suppression of ferroptosis, underscoring its pathway-dependent action. Corilagin alleviates myocardial I/R injury by activating the PI3K/AKT pathway to suppress ferroptosis, highlighting its potential as a therapeutic candidate for clinical translation.</div></div>","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":"1006 ","pages":"Article 178158"},"PeriodicalIF":4.7,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145080057","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}