European journal of pharmacology最新文献

{"title":"Discovery of the first isoform-specific sGC activator: Selective activation of GC-1 by runcaciguat","authors":"Svenja Stomberg ,&nbsp;Anne Rühle ,&nbsp;Theresa Wittrien ,&nbsp;Peter Sandner ,&nbsp;Sönke Behrends","doi":"10.1016/j.ejphar.2025.177557","DOIUrl":"10.1016/j.ejphar.2025.177557","url":null,"abstract":"<div><div>Drug research and development programmes targeting soluble guanylyl cyclase (sGC) have been highly successful, leading to the launch of the sGC stimulators riociguat for pulmonary hypertension (2013) and vericiguat for chronic heart failure (2021). As the main receptor for nitric oxide, sGC plays a vital role in various physiological processes. It consists of an alpha and a beta subunit, with two distinct isoforms identified in humans: GC-1 (α₁/β₁) and GC-2 (α₂/β₁). Growing evidence indicates that these isoforms engage in different downstream signalling pathways, indicating that isoform-specific approaches could lead to novel therapeutic opportunities and reduce potential side effects.</div><div>In this study, we performed concentration-response measurements with the sGC activators BAY 60–2770, BI 703704 and runcaciguat (BAY 1101042) in cell systems expressing each isoform and in purified enzymes. We found that runcaciguat selectively activated GC-1, while acting as a competitive antagonist to other activators in GC-2, without interfering with nitric oxide. BAY 60–2770 and BI 703704 activated both isoforms, albeit with varying efficacy.</div><div>Our findings challenge the historical view that the two sGC isoforms are functionally indistinguishable. In fact, we demonstrate that the isoforms can be activated independently, highlighting their distinct functional profiles. Notably, runcaciguat is the first sGC activator identified to selectively target GC-1 at therapeutic concentrations. This selective targeting of isoforms not only opens avenues for new therapeutic strategies but also provides an alternative to knockout animal models for investigating isoform-specific functions.</div></div>","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":"996 ","pages":"Article 177557"},"PeriodicalIF":4.2,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143729506","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Oligo-peptide I-C-F-6 mitigates polymicrobial sepsis-induced cardiac dysfunction in mice","authors":"Hongxiao Li ,&nbsp;Guang Li ,&nbsp;Yuan Gao ,&nbsp;Yulin Ma ,&nbsp;Zixuan Yu ,&nbsp;Anna Zhang ,&nbsp;Guoling Yang ,&nbsp;Zhiqi Hou ,&nbsp;Yuefan Zhang ,&nbsp;Yongsheng Yu ,&nbsp;Zhigang Zhang","doi":"10.1016/j.ejphar.2025.177545","DOIUrl":"10.1016/j.ejphar.2025.177545","url":null,"abstract":"<div><div>Cardiomyopathy accounts for worse clinical outcome and higher mortality rate during sepsis globally. Here we assessed whether post-operative administration of I-C-F-6, a small molecule oligo-peptide (Gly-Ala-Gly-Pro-His-Gly-Gly) derived from <em>Carapax trionycis</em>, protected against septic cardiomyopathy in mice. Male adult mice were exposed to cecal ligation and puncture (CLP) and I-C-F-6 was administered intravenously (0.4 mg/kg or 4.0 mg/kg) 30 min following surgery. Administration of I-C-F-6 extended survival period and decreased sepsis severity score in septic mice. Furthermore, administration of I-C-F-6 mitigated cardiac atrophy and preserved cardiac function in septic mice. Mechanistically, I-C-F-6 inhibited inflammation and promoted M2 polarization in myocardium of septic mice. In addition, I-C-F-6 activated nuclear factor erythroid 2-related factor 2 (Nrf2)/haem oxygenase-1 (HO-1)/glutathione peroxidase 4 (GPX4) pathway, mitigated oxidative damage and inhibited ferroptosis in myocardium of septic mice. In conclusion, post-operative administration of I-C-F-6 in mice exposed to CLP improved survival and mitigated myocardial impairment. Our work established a clear therapeutic potential of I-C-F-6 for sepsis-induced cardiomyopathy.</div></div>","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":"996 ","pages":"Article 177545"},"PeriodicalIF":4.2,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143729195","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":"Genistein reverses the exacerbating effect of 17β-estradiol on experimental occlusal interference induced chronic masseter hyperalgesia through suppressing ERK1/2 signal pathway in spinal trigeminal nucleus of ovariectomized rats","authors":"Si-Yi Mo ,&nbsp;Yuan Li ,&nbsp;Ying-Ying Fan ,&nbsp;Yao-Jun Zhang ,&nbsp;Jing-Wen Liu ,&nbsp;Xu-Tong Song ,&nbsp;Xiao-Xiang Xu ,&nbsp;Ye Cao ,&nbsp;Jian-Qiu Jin ,&nbsp;Qiu-Fei Xie","doi":"10.1016/j.ejphar.2025.177544","DOIUrl":"10.1016/j.ejphar.2025.177544","url":null,"abstract":"<div><h3>Background</h3><div>Temporomandibular disorder (TMD) pain is more prevalent in females than in males, with high estrogen levels potentially being a risk factor. Research indicates that 17β-estradiol (E2) exacerbates experimental occlusal interference (EOI)-induced orofacial hyperalgesia, which can be reversed by genistein. This study aimed to explore the central mechanisms within the spinal trigeminal nucleus (Sp5) related to the pain-exacerbating effect of E2 and the antiestrogenic properties of genistein in a model of EOI-induced chronic masseter pain.</div></div><div><h3>Methods</h3><div>Female rats underwent ovariectomy (OVX), followed by pretreatment with genistein or genistin (a control drug for genistein that does not inhibit protein tyrosine kinases (PTKs)), E2 replacement, and EOI application. The head withdrawal thresholds (HWTs) of the bilateral masseters were measured to evaluate pain sensitivity. Expression levels of p-ERK and two PTKs (Yes-associated protein, YAP; Src kinase, Src) in bilateral Sp5 were assessed through immunofluorescent staining and/or Western blotting. The ERK inhibitor PD98059 or vehicle was administered via intrathecal injection (i.t.) to inhibit the ERK1/2 signaling pathway.</div></div><div><h3>Results</h3><div>E2 intensified EOI-induced masseter mechanical hyperalgesia in OVX rats, and upregulated the phosphorylation of ERK1/2 in bilateral Sp5. Blocking phosphorylation of ERK1/2 in Sp5 reversed the exacerbating effect of E2. Genistein partially reversed the masseter hyperalgesia induced by E2 combined with EOI, possibly through the inhibition of PTKs and p-ERK1/2 upregulation in bilateral Sp5.</div></div><div><h3>Conclusion</h3><div>Genistein alleviates the pain-exacerbating effect of E2 on EOI-induced chronic mechanical hyperalgesia by inhibiting YAP and Src tyrosine kinases as well as the downstream ERK1/2 signaling pathway in Sp5.</div></div>","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":"998 ","pages":"Article 177544"},"PeriodicalIF":4.2,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143728766","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":"Dipeptidyl peptidase-4 inhibitors enhance memory retention via neuropeptide Y","authors":"Iulia Zoicas ,&nbsp;Stephan von Hörsten ,&nbsp;Anne-Christine Plank ,&nbsp;Johannes Kornhuber","doi":"10.1016/j.ejphar.2025.177556","DOIUrl":"10.1016/j.ejphar.2025.177556","url":null,"abstract":"<div><div>We have previously shown that neuropeptide Y (NPY) prolongs the retention of memory in the object discrimination test in mice. In this study, we investigated the potential memory-enhancing effects of dipeptidyl peptidase-4 (DPP4) inhibitors, commonly referred to as gliptins, which are known to prevent the degradation of NPY, thereby increasing its concentration. We show that administration of sitagliptin (50 and 100 mg/kg/day) and linagliptin (5 and 10 mg/kg/day) via the drinking water facilitates the retention of object memory in male CD1 mice, extending memory retention to time points when control mice no longer retain memory. Similar to gliptin-treated mice, male and female homozygous and heterozygous DPP4 deficient mice displayed intact object memory at time points when wild-type littermates showed no memory. Sitagliptin treatment, however, did not facilitate the retention of memory in male and female homozygous NPY deficient mice, indicating that NPY is essential for the memory-enhancing effects of sitagliptin. These results indicate that sitagliptin exerts memory-enhancing effects through an NPY-dependent mechanism and highlight the potential of gliptins as cognitive enhancers in healthy individuals.</div></div>","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":"996 ","pages":"Article 177556"},"PeriodicalIF":4.2,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143729505","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy of mangiferin, kaempferol, and diosgenin on models of depression: A systematic review and network meta-analysis of rodent studies","authors":"Lan Lei,&nbsp;Cong-Ya Chen,&nbsp;Yu-Fei Wang,&nbsp;Xuan Yang,&nbsp;Zhen-Yu Guo,&nbsp;Yi Zhang","doi":"10.1016/j.ejphar.2025.177555","DOIUrl":"10.1016/j.ejphar.2025.177555","url":null,"abstract":"<div><h3>Background</h3><div>Mangiferin (MGF), kaempferol (KMP), and diosgenin (DIO) are active compounds extracted from the dried rhizomes of <em>Anemarrhena asphodeloides</em> Bunge. that are proven to have antidepressant activity. However, no studies comprehensively compare and analyze the efficacy of MGF, KMP, and DIO.</div></div><div><h3>Methods</h3><div>We searched electronic databases (e.g., Cochrane Library, Embase, Scopus, and PubMed) for studies of three compounds in rodents from inception to October 2024, performing a systematic review and network meta-analysis. We used animal behavioral tests as outcome indicators, including the forced swimming test, tail suspension test, and sucrose preference test.</div></div><div><h3>Results</h3><div>A total of ten studies were included, involving 440 animals and six interventions. In the forced swimming test, the efficacy of fluoxetine was superior to KMP, MGF, and DIO. In the tail suspension test, DIO was more effective than fluoxetine, MGF, and KMP. In the sucrose preference test, the efficacy of fluoxetine was superior to MGF, DIO, and KMP. Specifically, MGF, KMP, and DIO significantly reduced the immobility time of the FST or TST and increased the sucrose preference index.</div></div><div><h3>Conclusions</h3><div>MGF, KMP, and DIO significantly improved depression-like behaviors of rodents, providing evidence for further development of new clinical antidepressants. Also, MGF, KMP, and DIO exert antidepressant effects primarily through anti-inflammatory, anti-oxidative stress, and regulation of neurotrophic factor and neurotransmitter levels.</div></div>","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":"997 ","pages":"Article 177555"},"PeriodicalIF":4.2,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143726274","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":"New perspectives on the treatment of diabetic nephropathy: Challenges and prospects of mesenchymal stem cell therapy","authors":"Canyu Chen ,&nbsp;Bo Xu ,&nbsp;Weiyi Li ,&nbsp;Jixiang Chen ,&nbsp;Mingxia Yang ,&nbsp;Lili Gao ,&nbsp;Jiecan Zhou","doi":"10.1016/j.ejphar.2025.177543","DOIUrl":"10.1016/j.ejphar.2025.177543","url":null,"abstract":"<div><div>Diabetic nephropathy (DN) is one of the most common microvascular complications of diabetes mellitus. Traditional treatment methods have certain limitations and it is difficult to effectively delay the disease progression. Mesenchymal stem cells (MSCs), owing to their potential for self-renewal, multidirectional differentiation, and immunomodulatory abilities, can regulate the renal immune microenvironment and repair damaged tissues, providing a new strategy for the treatment of DN. However, MSCs face problems such as immune rejection, cell inactivation, challenges in directed differentiation, insufficient homing ability, and low cell retention rate after delivery. These issues limit their clinical application in patients with DN. This review aims to propose optimization strategies targeting DN pathological features to improve MSC effectiveness and reduce their side effects. Specifically, it involves optimizing cell culture systems and cryopreservation protocols, along with pre-transplantation pharmacological conditioning to boost the functionality and viability of MSCs. Additionally, the exploration of synergistic drug-MSC combination therapies was carried out, taking advantage of diverse mechanisms of action to improve therapeutic outcomes. The integration of biomaterials and gene editing technologies to significantly enhance cell survival, target specificity, and tissue engraftment was also pursued. Concurrently, the determination of optimal therapeutic dosages and administration routes remained crucial. These multifaceted strategies not only provide a theoretical framework for overcoming existing technical limitations but also lay a robust foundation for accelerating the clinical translation of MSC-based therapies.</div></div>","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":"998 ","pages":"Article 177543"},"PeriodicalIF":4.2,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143725021","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":"Factors influencing the learning experience in pharmaceutical internships: A qualitative interview study.","authors":"Rozita Abdolrahimi Raeni, Arnout Jan de Beaufort, Anna Diewerke Arianna Pranger","doi":"10.1016/j.ejphar.2025.177530","DOIUrl":"https://doi.org/10.1016/j.ejphar.2025.177530","url":null,"abstract":"<p><strong>Introduction: </strong>experience-based learning (EBL) is the chosen educational strategy in the Master of Pharmacy curriculum at Leiden University. This strategy contributes to the development of the competence profile of a pharmacist by offering multiple internships. However, it is conceivable that what students learn during their internships may vary. This variability is an important issue that has not yet been investigated in literature. Therefore, the aim is to explore factors influencing learning experiences during pharmaceutical internships.</p><p><strong>Methods: </strong>we performed a descriptive qualitative study. We conducted semi-structured interviews (n=25) with Master of Pharmacy students (n=12), pharmaceutical internship supervisors (n=8), and curriculum stakeholders (n=5). The interviews were transcribed verbatim and coded in ATLAS.ti®, followed by thematic analysis.</p><p><strong>Results: </strong>we identified five themes influencing the learning experiences at pharmaceutical internships: (1) learning goals and experience (2) commitment, (3) diversity of the internships, (4) importance of the assessment, and (5) role of the curriculum. All three perspectives of the participants on the themes were aligned except for a discrepancy between the perspective of the curriculum stakeholders and the students about the safe learning environment.</p><p><strong>Conclusion: </strong>EBL reveals factors, (e.g. the student's dedication, the supervisor's involvement, uniformity in assessment and role of the curriculum) influencing learning experiences at pharmaceutical internships. The EBL strategy leads to variability between students' learning experiences that may lead to differences in competency development and may ultimately affect their readiness to work as a pharmacist. The factors that emerged from our research help to optimize the students' learning experiences during pharmaceutical internships.</p>","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":" ","pages":"177530"},"PeriodicalIF":4.2,"publicationDate":"2025-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143700001","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":"Targeting sensitive and multidrug resistant leukemia cells with a novel benzofuran-isatin conjugate","authors":"Chunmei Jin ,&nbsp;Mahmoud Emam ,&nbsp;Sabine M. Klauck ,&nbsp;Nadeen T. Ali ,&nbsp;Rofaida Salem ,&nbsp;Wagdy M. Eldehna ,&nbsp;Thomas Efferth ,&nbsp;Mohamed-Elamir F. Hegazy ,&nbsp;Mona Dawood","doi":"10.1016/j.ejphar.2025.177538","DOIUrl":"10.1016/j.ejphar.2025.177538","url":null,"abstract":"<div><div>Benzofuran-isatin conjugates are considered as promising compounds in cancer prevention and treatment. However, it is not known yet whether these compounds are useful to effectively treat multidrug-resistant tumors. In this study, we investigated the activity of <strong>G-5e</strong>, a novel benzofuran-isatin conjugate in a panel of cell lines exhibiting well-known drug resistance mechanisms (P-gp, BCRP, TP53, EGFR). P-glycoprotein overexpressing CEM/ADR5000 cell line displayed notable hypersensitivity (collateral sensitivity) to <strong>G-5e</strong>, which was mediated through autophagic cell death activation including downregulation of the autophagy suppressor RND2, upregulation of the autophagy inducer LC3B, and G0/G1 phase arrest during cell cycle progression. Independent of collateral sensitivity, transcriptomic analyses also revealed that <strong>G-5e</strong> caused downregulation of NF-κB and ERK1/2 pathways. Our findings highlight the potential of benzofuran-isatin conjugates to combat multidrug resistance and the role of RND2 for collateral sensitivity.</div></div>","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":"997 ","pages":"Article 177538"},"PeriodicalIF":4.2,"publicationDate":"2025-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143691417","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":"Melatonin induces urethral contraction and increases intraurethral pressure via MT1 receptor activation in female rats","authors":"Shigeo Matsui,&nbsp;Hiroko Yanai-Inamura,&nbsp;Masashi Kajiro,&nbsp;Hajime Takamatsu,&nbsp;Masayuki Tanahashi,&nbsp;Masanori Yokono","doi":"10.1016/j.ejphar.2025.177539","DOIUrl":"10.1016/j.ejphar.2025.177539","url":null,"abstract":"<div><div>Melatonin is released by the pineal gland and exerts numerous physiological effects via specific G protein-coupled receptors named MT₁ and MT₂ receptors. It is well known that melatonin acts as a key regulator of circadian rhythm through the activation of these receptors on the central nervous system. However, the expression and function of melatonin receptors in the lower urinary tract remain unclear. This study aimed to investigate the expression and function of melatonin receptors in female urethra. mRNA expression analysis exhibited high expression of MT₁ and MT₂ receptor mRNA in human and rat female urethra. A study of isolated female rat urethral tissue strips using melatonin receptor agonists and an antagonist strongly revealed that stimulation of melatonin MT₁ receptor induced urethral smooth muscle contraction. Further investigation of the mechanism underlying this melatonin MT₁ receptor-related urethral contraction demonstrated that stimulation of MT₁ receptors in urethra activates intracellular Ca²⁺ mobilization via G_q protein-dependent pathways, resulting in smooth muscle contraction. In vivo studies also revealed that melatonin receptor agonists induced an increase in urethral perfusion pressure in female rats. This is the first study to clearly demonstrate the expression and function of melatonin receptors in the urethra. These findings suggested that activation of MT₁ receptors could be a potential pharmacological target for modulation of urethral function.</div></div>","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":"998 ","pages":"Article 177539"},"PeriodicalIF":4.2,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143691150","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":"Rutin protects the pancreas from inflammatory injury and oncogene-driven tumorigenesis by inhibiting acinar to ductal metaplasia","authors":"Xueni Wang ,&nbsp;Mengyuan Gong ,&nbsp;Zeen Zhu ,&nbsp;Bo Zhang ,&nbsp;Liang Han ,&nbsp;Wei Li ,&nbsp;Zheng Wu ,&nbsp;Qingyong Ma ,&nbsp;Zheng Wang ,&nbsp;Weikun Qian","doi":"10.1016/j.ejphar.2025.177536","DOIUrl":"10.1016/j.ejphar.2025.177536","url":null,"abstract":"<div><div>Rutin is a valuable traditional Chinese medicine known for its anti-inflammatory and anticancer effects. It has been shown to be effective in treating various inflammation-associated diseases. Here, we investigated the influence of rutin on acute pancreatitis and tumorigenesis. Using C57BL/6J mice and Kras mutant transgenic mice, we induced pancreatitis and acinar regeneration models. Pancreatic malondialdehyde (MDA), superoxide dismutase (SOD) activity and reduced glutathione (GSH) contents were measured for oxidative stress. Histological staining and a pancreatic acinar 3D culture model were used to clarify the influence of rutin on ADM <em>in vivo</em> and <em>in vitro</em>. Western blotting was adopted to detect ADM markers amylase and CK19. We found that rutin ameliorated inflammatory injury to the pancreas in both caerulein<em>-</em> and arginine-induced AP. Then, we revealed that the anti-damage effect of rutin may be due to its inhibition of oxidative stress. In addition, an acinar 3D culture model showed that rutin inhibited the formation of ADM by activating AMPK in acinar cells. Finally, the activation of AMPK is believed to be a potential mechanism by which rutin exerts inhibitory effects on Kras-driven tumorigenesis. Rutin inhibited AP-induced pancreatic injury and oncogenic Kras-driven tumorigenesis by inhibiting ADM.</div></div>","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":"998 ","pages":"Article 177536"},"PeriodicalIF":4.2,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143691152","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}