European journal of pharmacology最新文献

{"title":"Peimisine ameliorates allergic asthma by suppressing Th2-associated inflammation and oxidative stress","authors":"Shu-Chen Cheng,&nbsp;Chian-Jiun Liou,&nbsp;Yun-Yi Guo,&nbsp;Po-Ting Lin,&nbsp;Wen-Chung Huang","doi":"10.1016/j.ejphar.2026.179085","DOIUrl":"10.1016/j.ejphar.2026.179085","url":null,"abstract":"<div><div><em>Fritillaria thunbergii</em> Miq. has been traditionally used to treat respiratory disorders in Chinese medicine. Peimisine, a major <em>F. thunbergii</em> alkaloid, has anti-inflammatory and antioxidant effects, but its role in allergic asthma and mucus-driven airway remodeling remains unclear.</div><div>This study investigated whether peimisine could attenuate asthmatic phenotypes and explored its mechanistic links to Th2 inflammation, epithelial activation, and oxidative stress. Female BALB/c mice were sensitized and challenged with ovalbumin (OVA) and treated with peimisine. Airway hyperresponsiveness (AHR) and lung function were measured, and lung tissues were evaluated for inflammatory infiltration, goblet cell hyperplasia/mucus hypersecretion, and remodeling. Inflammatory mediators and oxidative stress indices were determined in bronchoalveolar lavage fluid (BALF) and lung homogenates. In vitro, BEAS-2B bronchial epithelial cells were used to assess inflammatory activation, intracellular reactive oxygen species (ROS) generation, and monocyte–epithelial adhesion. Peimisine significantly improved AHR and reduced airway inflammatory cell infiltration. It also suppressed goblet cell expansion, mucus hypersecretion, and collagen deposition. Mechanistically, peimisine attenuated Th2-skewed inflammation, reducing BALF eosinophils, Th2 cytokines, eotaxins, and OVA-specific IgE/IgG1 while increasing Th1-associated markers and OVA-specific IgG2a. Peimisine restored redox balance and inhibited NF-κB activation in lung tissue. Consistently, peimisine downregulated epithelial eotaxins, ICAM-1, and pro-inflammatory cytokines in BEAS-2B cells, concomitant with reduced ROS production and diminished monocyte adhesion. Overall, peimisine alleviated allergic asthma by reducing airway inflammation and oxidative stress and by limiting Th2 immune activation, thereby decreasing epithelial inflammatory responses, mucus hypersecretion, and airway remodeling. These results suggest that peimisine may be a promising therapeutic candidate for allergic asthma.</div></div>","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":"1030 ","pages":"Article 179085"},"PeriodicalIF":5.7,"publicationDate":"2026-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148316369","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":"Valsartan repurposing to mitigate autoimmune encephalomyelitis via ACE2/Ang1-7/MasR axis pathway cognitive and neuroinflammation modulation; an experimental and chem-bio-informatics study","authors":"Mostafa A. Rabie,&nbsp;Rania M. Rahmo,&nbsp;Hekmat M. El Magdoub,&nbsp;Nadia M. Hamdy,&nbsp;Lobna H. Khedr","doi":"10.1016/j.ejphar.2026.179146","DOIUrl":"10.1016/j.ejphar.2026.179146","url":null,"abstract":"<div><div>Multiple sclerosis (MS) is a debilitating neuroinflammatory disease frequently associated with cognitive impairment. Recent research suggests that targeting the renin-angiotensin system (RAS) may offer a promising therapeutic strategy for alleviating cognitive deficits in neurodegenerative disorders. This study aimed to explore the interactions between valsartan (VAL), an angiotensin II receptor antagonist, ACE2/Ang 1–7/MasR signaling, and PI3K/Akt/CREB/BDNF pathway in preserving cognitive function using an experimental autoimmune encephalomyelitis (EAE) mouse model. EAE was induced in mice through spinal cord homogenate, leading to motor and cognitive impairments that mimic those observed in MS patients. In addition, comprehensive bioinformatics and chemo-bioinformatics analyses were conducted.</div><div>Oral administration of VAL (40 mg/kg/day) significantly ameliorated EAE-induced cognitive deficit in spatial and learning memory as evidenced by improved performance in the novel object recognition (NOR) and Morris water maze (MWM), along with a reduction in EAE clinical scoring. Histological analysis further revealed that VAL treatment mitigated EAE-induced demyelination in the corpus callosum.</div><div>Mechanistically, VAL activated ACE2/Ang 1-7/MasR signaling pathway, stimulating the p-PI3K/p-Akt/p-CREB axis, and consequently elevating BDNF, its receptor TrkB and synapsin I, thereby establishing a cycle of neuroprotection. Furthermore, VAL mitigated EAE-induced neuroinflammation by reducing p-NFκB p65, TNF-α and IL-6 contents, while restoring redox balance by enhancing SOD and GPx activities, elevating GSH content and reducing MDA content. Collectively, these findings highlight the potential of VAL in preserving cognitive function in EAE by modulating key neuroprotective and anti-inflammatory pathways, offering valuable insights into novel therapeutic strategies for MS and related neuroinflammatory disorders. These conclusions are further supported by complementary bioinformatics analyses.</div></div>","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":"1030 ","pages":"Article 179146"},"PeriodicalIF":5.7,"publicationDate":"2026-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148454994","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 impact of phytochemicals on statin efficacy and safety: A review","authors":"Pooya Vatankhah,&nbsp;Vahab Alamdari-Palangi,&nbsp;Mehdi Kian,&nbsp;Fatemeh Hosseinpour-Soleimani,&nbsp;Amir Savardshtaki,&nbsp;Amir Tajbakhsh,&nbsp;Mohammad Hashem Hashempur","doi":"10.1016/j.ejphar.2026.179129","DOIUrl":"10.1016/j.ejphar.2026.179129","url":null,"abstract":"<div><div>Statins are widely prescribed lipid-lowering agents but are associated with adverse effects such as myopathy and, less commonly, cognitive disturbances. Increasing evidence suggests that plant-derived phytochemicals can interact with statins, producing both beneficial and potentially harmful effects. Preclinical and limited clinical evidence suggests that selected phytochemicals may enhance certain therapeutic effects of statins and may contribute to adverse effect mitigation; however, their potential to support statin dose reduction requires confirmation in well-designed clinical trials. Phytochemicals may reduce inflammation and oxidative stress, potentially enabling lower statin doses. By elucidating these interactions, healthcare providers can develop personalized treatment strategies that enhance therapeutic outcomes of statins while minimizing risks. This review aims to clarify the intricate relationship between specific phytochemicals and statins, emphasizing the need for further investigation into their combined effects on cardiovascular health. The strength of evidence varies considerably across the available literature, ranging from randomized controlled trials to preclinical <em>in vitro</em> and animal studies. Consequently, the translational applicability of many reported phytochemical–statin interactions remains uncertain and warrants further clinical investigation. In addition to potentially beneficial effects, several phytochemicals may pose clinically relevant safety concerns through mechanisms, such as CYP3A4 inhibition, leading to increased statin exposure and toxicity; OATP inhibition, potentially reducing hepatic statin uptake and therapeutic efficacy; and hERG channel blockade, which may increase the risk of QT prolongation. These interactions may contribute to adverse outcomes, including statin-associated myopathy and, in rare cases, rhabdomyolysis.</div></div>","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":"1030 ","pages":"Article 179129"},"PeriodicalIF":5.7,"publicationDate":"2026-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148454904","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":"L-carnosine attenuates endometrial fibrosis by targeting the ERK/PTGS2 axis","authors":"Yaru Zhu,&nbsp;Xi'er Zhang,&nbsp;Xinyu Zhang,&nbsp;Qinhong Zhuang,&nbsp;Xinya Wang,&nbsp;Xin Zhang,&nbsp;Yali Hu,&nbsp;Dan Liu,&nbsp;Guangfeng Zhao","doi":"10.1016/j.ejphar.2026.179089","DOIUrl":"10.1016/j.ejphar.2026.179089","url":null,"abstract":"<div><h3>Aim</h3><div>Intrauterine adhesions (IUA) remain a significant clinical challenge, as current surgical interventions are limited by high recurrence rates. While metabolic dysregulation is implicated in various fibrotic diseases, its specific role in IUA pathogenesis remains largely unexplored. In this study, metabolomic analysis revealed a marked depletion of L-carnosine in IUA patients, prompting us to investigate its pathophysiological role and therapeutic potential.</div></div><div><h3>Methods</h3><div>We evaluated the anti-fibrotic effects of L-carnosine in vitro using TGF-β-induced human endometrial stromal cells (hESCs) and in vivo using a mouse model of IUA. Subsequently, RNA-seq was performed on hESCs to compare the TGF-β-treated group with the TGF-β plus L-carnosine group, aiming to identify differentially expressed genes and enriched signaling pathways, thereby elucidating the molecular mechanisms by which L-carnosine attenuates endometrial fibrosis.</div></div><div><h3>Results</h3><div>We demonstrated that L-carnosine treatment effectively reversed TGF-β-induced fibrosis in hESCs in vitro and attenuated uterine fibrosis in an IUA mouse model in vivo. Mechanistically, the anti-fibrotic effects of L-carnosine were mediated by the inhibition of ERK phosphorylation, which subsequently led to increased the expression of prostaglandin-endoperoxide synthase 2 (PTGS2). The functional importance of this ERK/PTGS2 axis was validated: exogenous PGE2 (the major product of PTGS2) mimicked the anti-fibrotic effects, whereas inhibition of PTGS2 with celecoxib (a specific PTGS2 inhibitor) abrogated the protective effects of L-carnosine. Conversely, pharmacological activation of ERK using mSIRK (an ERK activator) blunted the L-carnosine-induced upregulation of PTGS2.</div></div><div><h3>Conclusion</h3><div>These findings identify L-carnosine depletion as a pivotal metabolic hallmark of IUA and position L-carnosine supplementation as a viable anti-fibrotic strategy by specifically targeting the ERK/PTGS2 pathway.</div></div>","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":"1030 ","pages":"Article 179089"},"PeriodicalIF":5.7,"publicationDate":"2026-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148316421","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":"Maresin-1 protects against lipopolysaccharide (LPS)-induced depressive-like behavior in adolescent mice and promotes M2 microglial polarization via ERK/NF-κB signaling","authors":"Jiamei Guo,&nbsp;Xiang Cao,&nbsp;Chenxi Liu,&nbsp;Feng Chen,&nbsp;Zixuan Ye,&nbsp;Tian Qiu","doi":"10.1016/j.ejphar.2026.179093","DOIUrl":"10.1016/j.ejphar.2026.179093","url":null,"abstract":"<div><div>Adolescence is a critical developmental stage characterized by heightened vulnerability to psychiatric symptoms associated with neuroimmune challenges. Maresin-1 (MaR1), a specialized pro-resolving mediator, exerts potent anti-inflammatory actions; however, its effects on inflammation-associated mood-related behavioral alterations during adolescence remain unclear. This study investigated the prophylactic effects of MaR1 in a lipopolysaccharide (LPS)-induced acute inflammatory challenge model using male adolescent C57BL/6J mice. MaR1 (5 μg/kg, i.p.) was administered 1 h before LPS challenge, and behavioral assessments were conducted 24 h later, a time point selected to reduce, but not eliminate, potential confounding by acute sickness-like responses. MaR1 pretreatment attenuated LPS-induced reductions in sucrose preference and increases in tail suspension immobility. MaR1 also reduced hippocampal inflammatory responses, as indicated by decreased TNF-α and IL-1β levels and changes in M1/M2-associated microglial marker profiles. Whole hippocampal tissue analyses showed that MaR1 dampened LPS-induced hippocampal ERK/NF-κB activation in vivo, while BV-2 cell experiments showed that MaR1 suppressed LPS-induced ERK and NF-κB phosphorylation in vitro. The MEK inhibitor U0126 partially mimicked the behavioral and inflammatory effects of MaR1, and co-administration did not produce additive behavioral benefits, consistent with the involvement of an ERK-related component. Collectively, these findings suggest that MaR1 pretreatment mitigates LPS-induced inflammation-associated depressive-like behavioral alterations in male adolescent mice, accompanied by reduced hippocampal inflammatory signaling and modulation of microglia-associated inflammatory marker profiles. These results support further investigation of MaR1 and related pro-resolving mediators as candidate modulators of inflammation-associated mood-related disturbances during development.</div></div>","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":"1030 ","pages":"Article 179093"},"PeriodicalIF":5.7,"publicationDate":"2026-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148338377","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":"Phosphorylated HAND1 contributes to trophoblast cell migration during placentation by activating the Vav2-Rac1-PAK signaling","authors":"Weifeng Ye,&nbsp;Chongying Zhu,&nbsp;Yiyao Bao,&nbsp;Lin Li,&nbsp;Zihao An,&nbsp;Yan Song,&nbsp;Qiang Xu,&nbsp;Meiyuan Jin,&nbsp;Chao Tang","doi":"10.1016/j.ejphar.2026.179096","DOIUrl":"10.1016/j.ejphar.2026.179096","url":null,"abstract":"<div><div>Trophoblastic cell migration is essential for the attachment of the placenta to uterine wall, which is a critical step for fetal development. Aberrant migration of trophoblastic cells can lead to pregnant pathologies such as preeclampsia (PE), while the molecular mechanisms remain largely unknown. The current study investigated the effects and molecular mechanisms of the HAND1-Rac1-PAK axis in trophoblast migration using the HTR-8/SVneo cell line, isolated human primary cytotrophoblasts, and human placental tissues. We report herein that HAND1 is highly expressed in human early placenta and promotes trophoblastic cell migration. Mechanistically, HAND1 potentiates human trophoblastic cell migration via activating Vav2/Rac1/PAKs signaling, and the elevated capacity of HAND1 in inducing migration is dependent on its Serine/Threonine phosphorylation status, which is reciprocally regulated by PAK2 and is directly associated with the subsequent degradation of HAND1 protein, thereby generating a positive feed-back for HAND1-mediated trophoblasts migration during human pregnancy. The data suggest that HAND1 is essential for regulating human trophoblast function, potentially enhancing our understanding of pregnancy maintenance and contributing to new therapies for gestational disorders.</div></div>","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":"1030 ","pages":"Article 179096"},"PeriodicalIF":5.7,"publicationDate":"2026-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148338383","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":"Network pharmacology and in vivo validation reveal the protective mechanism of 6-gingerol against diabetic encephalopathy","authors":"Rui-Xuan Liu,&nbsp;Fang-Cheng Cheng,&nbsp;Tian-Shu Zhang,&nbsp;Ze-Yu Li,&nbsp;Jian-Hua Ge,&nbsp;Hai-Min Wang,&nbsp;Feng Wang,&nbsp;Hao Wang,&nbsp;Ji-Guo Zhang,&nbsp;Feng Zhang","doi":"10.1016/j.ejphar.2026.179101","DOIUrl":"10.1016/j.ejphar.2026.179101","url":null,"abstract":"<div><div>Diabetic encephalopathy (DE) is a prevalent and severe neurological complication associated with the advanced stages of type 2 diabetes mellitus (T2DM). Its pathogenesis is multifactorial and not yet fully understood, and currently, there are no effective therapeutic interventions available. 6-Gingerol, a natural phenolic compound derived from ginger, exhibits favorable brain-targeting properties and diverse pharmacological activities, making it a promising candidate for the treatment of DE. In this study, the multi-target mechanism of 6-gingerol in DE was systematically investigated by integrating network pharmacological analysis with in vivo experimental validation. Network pharmacology results identified PPARG (namely PPARγ), mTOR, and ESR1 as key core targets of 6-gingerol, which were primarily enriched in pathways related to inflammatory regulation, amyloid-β metabolism, and neuroprotection. Animal experiments demonstrated that four weeks of 6-gingerol treatment significantly reduced fasting blood glucose (FBG), total cholesterol (TC), triglycerides (TG) and body weight, while improving cognitive function in 13-week-old db/db mice. Additionally, 6-gingerol markedly attenuated neuroinflammatory responses and decreased soluble amyloid-β levels in the hippocampus. Notably, partial beneficial effects of 6-gingerol were significantly attenuated by GW9662 (a selective PPARγ antagonist), while pioglitazone (a well-known PPARγ agonist) replicated the neuroprotective effects of 6-gingerol in multiple pathological endpoints. Collectively, these findings imply that 6 - gingerol may exert its protective effect against DE via a multi-target synergistic mechanism in which PPARγ plays a key regulatory role.</div></div>","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":"1030 ","pages":"Article 179101"},"PeriodicalIF":5.7,"publicationDate":"2026-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148351399","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":"Theranekron prevents endotoxin-induced acute kidney injury by modulating inflammatory and mitochondrial apoptotic pathways","authors":"Atila Altuntas,&nbsp;Halil Asci,&nbsp;Ilter Ilhan,&nbsp;Sefa Alperen Ozturk,&nbsp;Esra Sirazi,&nbsp;Ozlem Ozmen,&nbsp;Zeynep Akpınar,&nbsp;Dudu Seher Yurt","doi":"10.1016/j.ejphar.2026.179100","DOIUrl":"10.1016/j.ejphar.2026.179100","url":null,"abstract":"<div><h3>Background</h3><div>Lipopolysaccharide (LPS)–induced acute kidney injury (AKI) is characterized by oxidative stress, inflammation, and apoptotic injury. Theranekron (THERA) has been suggested to exert immunomodulatory effects; however, its impact on renal oxidative status and related molecular pathways remains unclear.</div></div><div><h3>Methods</h3><div>Thirty-two male Wistar albino rats were allocated into four groups: Control, LPS, LPS + THERA, and THERA. Renal oxidative stress was assessed by measuring total antioxidant status (TAS), total oxidant status (TOS), and oxidative stress index (OSI). Serum creatinine and urea levels, histopathological alterations, and immunohistochemical expression of endothelial nitric oxide synthase (eNOS), interferon-gamma (IFN-γ), and interleukin-8 (IL-8) were evaluated. Sirtuin-1 (SIRT1), nuclear factor erythroid 2–related factor 2 (NRF2), heme oxygenase-1 (HO-1), B-cell lymphoma-2 (BCL2), BCL2-associated X protein (BAX), aquaporin-2 (AQP2), tumor necrosis factor-alpha (TNF-α), and interleukin-10 (IL-10) gene expression were measured.</div></div><div><h3>Results</h3><div>LPS significantly increased urea and creatinine levels and induced marked renal histopathological injury. Renal TAS was significantly decreased, and OSI was significantly increased. THERA treatment significantly increased TAS and reduced OSI compared with the LPS group. LPS significantly reduced SIRT1, NRF2, and HO-1 mRNA expression, and prophylactic THERA treatment significantly increased only HO-1 expression. LPS induced a pro-apoptotic shift and reduced AQP2 expression, all of which were significantly prevented by THERA. In parallel, THERA significantly reduced TNF-α expression and IL-10 levels, decreased IFN-γ and IL-8 immunoreactivity, and reduced eNOS immunoreactivity.</div></div><div><h3>Conclusion</h3><div>Prophylactic THERA administration partially protected against early renal injury by improving renal antioxidant capacity, upregulating HO-1, and suppressing inflammatory and apoptotic responses, with preservation of AQP2 expression.</div></div>","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":"1030 ","pages":"Article 179100"},"PeriodicalIF":5.7,"publicationDate":"2026-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148359929","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":"Astaxanthin inhibits platelet-mediated thrombosis via suppression of bidirectional αIIbβ3 signaling","authors":"Hado Choi,&nbsp;Yeon-Ji Kim,&nbsp;Hyun Woung Shin,&nbsp;Sang Mok Jung,&nbsp;Kyungho Kim","doi":"10.1016/j.ejphar.2026.179109","DOIUrl":"10.1016/j.ejphar.2026.179109","url":null,"abstract":"<div><div>Platelets are central mediators of hemostasis and thrombosis, and dysregulated platelet activation substantially contributes to the pathogenesis of cardiovascular diseases. Astaxanthin (AZ), a xanthophyll carotenoid and a bioactive compound derived from <em>Haematococcus lacustris</em>, possesses potent antioxidant and anti-inflammatory properties. Nevertheless, its regulatory effects on platelet function remain insufficiently elucidated. This study investigated the impact of AZ on platelet function and thrombosis. In vitro experiments demonstrated that AZ significantly inhibited agonist-induced platelet aggregation, secretion of dense and α-granules, intracellular calcium mobilization, αIIbβ3 integrin activation, platelet spreading, and clot retraction. In addition, AZ reduced intracellular reactive oxygen species (ROS) generation under collagen-related peptide (CRP)-stimulated platelet activation in a concentration-dependent manner. Mechanistic analyses revealed that AZ suppressed the phosphorylation of key kinases involved in the bidirectional signaling of αIIbβ3 integrin, including spleen tyrosine kinase (Syk), phospholipase C (PLC), phosphoinositide 3-kinase (PI3K), Akt, proline-rich tyrosine kinase 2 (Pyk2), and focal adhesion kinase (FAK). <em>In vivo</em>, oral administration of AZ significantly prolonged FeCl₃-induced carotid artery occlusion time and tail bleeding time. Collectively, these findings suggest that AZ modulates platelet activation and thrombosis through coordinated effects on integrin-associated signaling, intracellular kinase phosphorylation, and redox-related regulatory mechanisms.</div></div>","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":"1030 ","pages":"Article 179109"},"PeriodicalIF":5.7,"publicationDate":"2026-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148374883","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":"Repurposing of alogliptin to mitigate experimentally-induced ulcerative colitis and its associated pulmonary injury in rats through regulating inflammatory, necroptotic, and ER stress pathways","authors":"Manar A. Didamoony,&nbsp;Mustafa M. Shokr,&nbsp;Reem M. Eladawy,&nbsp;Lamiaa A. Ahmed","doi":"10.1016/j.ejphar.2026.179113","DOIUrl":"10.1016/j.ejphar.2026.179113","url":null,"abstract":"<div><div>Lung injury is one of the clinically reported conditions associated with inflammatory bowel diseases. The purpose of this study was to assess, for the first time, alogliptin's possible therapeutic effect in acetic acid (AA)-induced UC and its associated lung injury in rats, with investigation of the probable molecular mechanisms of protection. To induce UC, rats were given a single intrarectal injection of 1 ml of 4% AA. Following 24 h of induction, rats were treated orally with ALO for 2 weeks at doses of 15 or 30 mg/kg/day. Higher-dose of ALO provided an ancillary improvement towards the treatment of AA-induced UC and its associated lung injury compared to lower-dose of ALO. Notably, ALO improved the rats' overall health, body weights and mitigated the pathological changes induced by AA in the colon and lungs. Besides, ALO enhanced tight junction integrity by modulating the gut DPP-4/GLPs axis, which in turn led to inhibition of systemic inflammation induced by TNF-α/claudin-1 axis. These outcomes subsequently prevented the pulmonary injury associated with TLR4/NF-κB p65/TNF-α, RIPK1/MLKL/HMGB1, IRE-1α/p-JNK, oxidative stress, and TGF-β1/COL1A1/COL3A1 cascades with notable anti-fibrotic effects. In this context, ALO could be a promising nominee for the treatment of UC and its associated pulmonary injury through attenuating colonic inflammation, preserving gut integrity, and preventing systemic inflammation and its associated lung-induced injury.</div></div>","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":"1030 ","pages":"Article 179113"},"PeriodicalIF":5.7,"publicationDate":"2026-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148374933","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}