European journal of pharmacology最新文献

{"title":"Dipeptidyl peptidase 3 induces myocardial ischemia-reperfusion injury by mediating mitophagy and the intrinsic apoptotic pathway","authors":"Xiao Wang,&nbsp;Yaofeng Xie,&nbsp;Hongjiao Du,&nbsp;Cheng Chang,&nbsp;Chunyang Tian,&nbsp;Yuyao Yin,&nbsp;Xiaodong Li,&nbsp;Yilong Pan","doi":"10.1016/j.ejphar.2025.177592","DOIUrl":"10.1016/j.ejphar.2025.177592","url":null,"abstract":"<div><h3>Background</h3><div>Dipeptidyl peptidase 3 (DPP3) is a zinc-dependent hydrolase that is regarded as a “myocardial inhibitor”. However, the role of DPP3 in myocardial ischemia-reperfusion injury (MIRI) remain to be investigated. The present study aimed to investigate the potential role of DPP3 in MIRI and elucidate the underlying mechanisms.</div></div><div><h3>Methods</h3><div>The AC16 cardiomyocyte cell line was used to investigate the interactions between DPP3 and its protein interactors, and assess its effects on the apoptosis of cardiomyocytes following oxygen glucose deprivation/reperfusion (OGD/R) treatment <em>in vitro</em>. An animal model of ischemia/reperfusion (I/R) injury was established using C57BL/6J mice for <em>in vivo</em> analyses. The role of DPP3 and the underlying mechanisms were investigated both <em>in vitro</em> and <em>in vivo</em> following DPP3 knockdown and overexpression.</div></div><div><h3>Results</h3><div>DPP3 interacted with Parkinson’s disease protein 7 (Park7), and DPP3 overexpression altered the expression levels of proteins related to the intrinsic apoptotic pathway and autophagy. This significantly downregulated the mitochondrial expression of cytochrome C, thereby exacerbating mitochondrial injury and increasing the rate of apoptosis following reperfusion. DPP3 knockdown reversed these effects; however, the simultaneous knockdown of DPP3 and Park7 did not confer the beneficial effects observed with DPP3 knockdown alone. DPP3 knockdown alleviated the extent of myocardial injury and improved cardiac function in the mouse model of I/R injury.</div></div><div><h3>Conclusions</h3><div>The study demonstrated that DPP3 mediates mitophagy and apoptosis in MIRI through its interaction with Park7. These findings have important implications, suggesting that targeting DPP3 and its associated signaling pathways may serve as a potential therapeutic strategy, and that the downregulation of DPP3 can potentially alleviate MIRI.</div></div>","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":"997 ","pages":"Article 177592"},"PeriodicalIF":4.2,"publicationDate":"2025-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143794554","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 sodium-glucose cotransporter 2 inhibitor tofogliflozin induces vasodilation of rabbit femoral artery by activating Kv channels, the SERCA pump, and the sGC/cGMP pathway","authors":"Wenwen Zhuang ,&nbsp;Minju Park ,&nbsp;Junsu Jeong ,&nbsp;Hye Ryung Kim ,&nbsp;YeEun Jang ,&nbsp;Mi Seon Seo ,&nbsp;Jin Ryeol An ,&nbsp;Hongzoo Park ,&nbsp;Won-Kyo Jung ,&nbsp;Il-Whan Choi ,&nbsp;Won Sun Park","doi":"10.1016/j.ejphar.2025.177595","DOIUrl":"10.1016/j.ejphar.2025.177595","url":null,"abstract":"<div><div>Tofogliflozin is a sodium-glucose cotransporter 2 inhibitor widely used to treat type 2 diabetes mellitus, but it also exhibits cardio-protective effects. This study investigated the vasodilatory action of tofogliflozin using rabbit femoral artery rings pre-contracted with phenylephrine (1 μM). The results showed the concentration-dependent induction of vasodilation by tofogliflozin, a response that remained unchanged following endothelial removal, pretreatment with the nitric oxide synthase inhibitor L-NAME (100 μM), or the inhibition of low- and intermediate-conductance Ca²⁺-activated K⁺ channels using apamin (1 μM) in combination with TRAM-34 (1 μM). Furthermore, pretreatment with the voltage-dependent K⁺ (Kv) channel inhibitor 4-AP (3 mM) reduced the vasodilatory effects of tofogliflozin whereas pretreatment with the ATP-sensitive K⁺ channel inhibitor glibenclamide (10 μM) or the large-conductance Ca²⁺-activated K⁺ channel inhibitor paxilline (1 μM) did not. Notably, our findings indicated that Kv7.X, rather than Kv1.5 or Kv2.1, is the primary Kv subtype involved in tofogliflozin-induced vasodilation. The vasodilatory effects of tofogliflozin were also significantly inhibited in femoral arterial rings pretreated with the sarco/endoplasmic reticulum Ca²⁺-ATPase (SERCA) pump inhibitors thapsigargin (1 μM) and cyclopiazonic acid (10 μM). Tofogliflozin-induced vasodilation was unaltered in arterial rings exposed to the adenylyl cyclase inhibitor SQ 22536 (50 μM), the protein kinase A (PKA) inhibitor KT 5720 (1 μM), and the protein kinase G inhibitor KT 5823 (1 μM) whereas it was effectively reduced by the soluble guanylyl cyclase (sGC) inhibitor ODQ (10 μM). These findings suggest that tofogliflozin-induced vasodilation is mediated by the activation of the SERCA pump, the sGC/cGMP pathway, and Kv channels.</div></div>","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":"996 ","pages":"Article 177595"},"PeriodicalIF":4.2,"publicationDate":"2025-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143792309","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":"Fisetin and resveratrol exhibit senotherapeutic effects and suppress cellular senescence in osteoarthritic cartilage-derived chondrogenic progenitor cells","authors":"Justin Jacob ,&nbsp;Aditya Aggarwal ,&nbsp;Shalmoli Bhattacharyya ,&nbsp;Daisy Sahni ,&nbsp;Vinit Sharma ,&nbsp;Anjali Aggarwal","doi":"10.1016/j.ejphar.2025.177573","DOIUrl":"10.1016/j.ejphar.2025.177573","url":null,"abstract":"<div><div>Chondrogenic progenitor cells (CPCs) in the articular cartilage of knee osteoarthritis (OA) patients exhibit cellular senescence and its associated secretory phenotype (SASP). We hypothesized that the senescence of CPCs can be suppressed using natural compounds. This study aimed to evaluate the senotherapeutic effects of fisetin and resveratrol to suppress the cellular senescence in CPCs. <em>In vitro</em>, pre-treatment of CPCs with increasing doses of fisetin and resveratrol (5μM–100μM) were non-cytotoxic, decreased the senescence index and dampened the expression of cellular senescence markers, p53 and p38MAPK. Additionally, SASP-related genes and proteins (MMP-9, MMP13) and inflammatory mediators (IL-1β, TGF-β, and IL-6) were downregulated. Further, <em>in silico</em> analysis confirmed the high binding affinity of these natural drugs to OA-related proteins. Overall, fisetin and resveratrol dampened the senescence of CPCs by downregulating the p53 effector protein and effectively reducing the SASP. From this study, natural compound candidates proved to be potential drug candidates that suppress senescence via p53.</div></div>","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":"997 ","pages":"Article 177573"},"PeriodicalIF":4.2,"publicationDate":"2025-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143794773","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":"FKBP5 mediates glucocorticoid signaling in estrogen deficiency-associated endothelial dysfunction","authors":"Ruiwen Zhu ,&nbsp;Yiyue Xu ,&nbsp;Huixian Li ,&nbsp;Chufeng He ,&nbsp;Fung Ping Leung ,&nbsp;Lin Wang ,&nbsp;Wing Tak Wong","doi":"10.1016/j.ejphar.2025.177598","DOIUrl":"10.1016/j.ejphar.2025.177598","url":null,"abstract":"<div><h3>Background</h3><div>Cardiovascular disease (CVD) is the leading cause of mortality among postmenopausal women, with atherosclerosis being a major underlying factor. Endothelial dysfunction, a key initiating event in atherosclerosis, can be triggered by hormonal and metabolic changes. While estrogen deficiency has been linked to increased cardiovascular risk, the molecular mechanisms by which it exacerbates endothelial dysfunction, particularly in the presence of elevated glucocorticoid levels, remain poorly understood. This study aims to explore the role of FK506-binding protein 5 (FKBP5) in mediating glucocorticoid-induced endothelial dysfunction in estrogen-deficient females.</div></div><div><h3>Methods</h3><div>Estrogen deficiency was developed in female mice by ovariectomy (OVX). Female mice and human umbilical vein endothelial cells (HUVECs) were treated with dexamethasone (DEX) to mimic elevated cortisol levels <em>in vivo</em> and <em>vitro</em>. Endothelial function of the mice aorta was assessed using wire myography. Oxidative stress and inflammation were evaluated through reactive oxygen species (ROS) detection, immunofluorescence and mRNA expression analysis. The selective FKBP5 inhibitor SAFit2 was used to study the functional role of FKBP5 in these processes.</div></div><div><h3>Results</h3><div>Estrogen deficiency contributed to endothelial dysfunction in female mice, an effect exacerbated by elevated glucocorticoid levels. FKBP5 expression was upregulated in both ovariectomized mice aortas and DEX-treated endothelial cells. Inhibition of FKBP5 reversed endothelial dysfunction, reduced ROS levels, and suppressed the expression of pro-inflammatory mediators, including ICAM-1, IL-1β, TNF-α, and NF-κB.</div></div><div><h3>Conclusion</h3><div>FKBP5 mediates glucocorticoid-induced endothelial dysfunction under estrogen-deficient conditions. Inhibition of FKBP5 represents a promising therapeutic strategy to ameliorate endothelial dysfunction and improve vascular health in estrogen-deficient women.</div></div>","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":"996 ","pages":"Article 177598"},"PeriodicalIF":4.2,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143785964","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":"Effects of decrease in Klotho protein expression on insulin signaling and levels of proteins related to brain energy metabolism","authors":"Ana Maria Marques Orellana ,&nbsp;Caio Henrique Mazucanti ,&nbsp;Diana Zukas Andreotti ,&nbsp;Larissa de Sá Lima ,&nbsp;Elisa Mitiko Kawamoto ,&nbsp;Cristoforo Scavone","doi":"10.1016/j.ejphar.2025.177587","DOIUrl":"10.1016/j.ejphar.2025.177587","url":null,"abstract":"<div><div>Mutations in Klotho have been associated with premature ageing and cognitive dysfunction. Although highly expressed in specific regions of the brain, the actions of Klotho in the central nervous system (CNS) remain largely unknown. Here, we show that animals with a mutated hypomorphic Klotho gene have altered glycaemic regulation, suggesting higher insulin sensitivity. In the CNS, pathways related to insulin intracellular signalling were found to be up-regulated in the hippocampus, with higher activation of protein kinase B and mammalian target of rapamycin and inactivation of the transcription factors forkhead box O (FOXO)-1 and FOXO-3a. In addition, the present study showed that in the hippocampi of wild-type aged mice, where Klotho is naturally downregulated, the levels of some proteins related to energy metabolism and metabolic coupling between neurones and astrocytes, such as monocarboxylate transporter 2 and 4, 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase isoform 3 and lactate dehydrogenase enzymes isoforms A and B were altered. These findings suggest that Klotho plays an essential role in regulating proteins and genes related to metabolic coupling in the brain.</div></div>","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":"997 ","pages":"Article 177587"},"PeriodicalIF":4.2,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143788241","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":"Unravelling soluble (pro)renin receptor-mediated endothelial dysfunction","authors":"Lachlan G. Schofield ,&nbsp;Juyi Zhao ,&nbsp;Yu Wang ,&nbsp;Sarah J. Delforce ,&nbsp;Saije K. Endacott ,&nbsp;Eugenie R. Lumbers ,&nbsp;Dan Ma ,&nbsp;Kirsty G. Pringle","doi":"10.1016/j.ejphar.2025.177601","DOIUrl":"10.1016/j.ejphar.2025.177601","url":null,"abstract":"<div><h3>Background</h3><div>Preeclampsia is characterized by maternal endothelial dysfunction and new-onset hypertension. Preeclamptic pregnancies have elevated levels of maternal soluble prorenin receptor (s(P)RR) and previous studies have shown that recombinant s(P)RR produces hypertension and vascular dysfunction. This study aimed to investigate the effects of PRO20, an s(P)RR antagonist, on s(P)RR-induced endothelial dysfunction and its interaction with the Angiotensin II Type 1 Receptor (AT₁R).</div></div><div><h3>Methods</h3><div>Human uterine microvascular endothelial cells (HUtMECs) were treated with 100 nM s(P)RR, with/without 10 nM PRO20, 10 μM Losartan (AT₁R antagonist), or 10 μM Aliskerin (renin inhibitor). The ability of PRO20 to prevent endothelial dysfunction induced by patient serum from preeclamptic pregnancies was also assessed. Endothelial dysfunction markers were measured using immunoblot, qPCR, and ELISA. For AT₁R mechanism studies, HUtMECs were treated with control or AT₁R siRNA before s(P)RR exposure. AT₁R and s(P)RR protein structures were predicted via AlphaFold-2 and docking examined using Schrödinger.</div></div><div><h3>Results</h3><div>PRO20 mitigated s(P)RR-induced increases in the mRNA expression of endothelial dysfunction markers, endothelin-1, VCAM-1 and ICAM-1 and prevented s(P)RR and preeclamptic serum-induced increases in endothelin-1 and VCAM-1 protein. Aliskerin had no effect on s(P)RR-induced endothelial dysfunction. Losartan and an AT₁R siRNA were able to prevent s(P)RR induced increases in VCAM-1 protein levels and ET-1 mRNA expression, respectively. Modelling suggested that PRO20 can impair s(P)RR-AT₁R complex formation.</div></div><div><h3>Conclusions</h3><div>Elevated s(P)RR induces endothelial dysfunction at least partially through AT₁R. PRO20 prevents s(P)RR-AT₁R formation, suggesting it could be an effective therapeutic for preeclampsia and conditions requiring renin-angiotensin system suppression.</div></div>","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":"996 ","pages":"Article 177601"},"PeriodicalIF":4.2,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143788271","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":"The protective effect of amylin in type 2 diabetes: Yes or no","authors":"Mansour Alanazi ,&nbsp;Hayder M. Al-Kuraishy ,&nbsp;Ali K. Albuhadily ,&nbsp;Ali I. Al-Gareeb ,&nbsp;Ahmed M. Abdelaziz ,&nbsp;Athanasios Alexiou ,&nbsp;Marios Papadakis ,&nbsp;Gaber El-Saber Batiha","doi":"10.1016/j.ejphar.2025.177593","DOIUrl":"10.1016/j.ejphar.2025.177593","url":null,"abstract":"<div><div>Amylin, which is also called a human islet amyloid polypeptide, is a peptide hormone made up of 37 amino acids that is released from pancreatic β cells. It helps keep blood sugar levels stable by controlling the release of insulin and glucagon. Various studies have indicated its involvement in the pathogenesis of type 2 diabetes (T2D) through the induction of apoptosis in pancreatic cells. Conversely, other studies found that amylin plays a critical role in the pathogenesis of T2D by affecting the release of insulin and glucagon. Therefore, amylin has protective and detrimental effects on the pathogenesis of T2D. Consequently, this review aims to discuss the beneficial and detrimental roles of amylin in T2D.</div></div>","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":"996 ","pages":"Article 177593"},"PeriodicalIF":4.2,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143788266","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":"Chrysin's anti-inflammatory action in the central nervous system: A scoping review and an evidence-gap mapping of its mechanisms","authors":"Lucian Del Fabbro ,&nbsp;Vandreza Cardoso Bortolotto ,&nbsp;Luana Mota Ferreira ,&nbsp;Marcel Henrique Marcondes Sari ,&nbsp;Ana Flávia Furian","doi":"10.1016/j.ejphar.2025.177602","DOIUrl":"10.1016/j.ejphar.2025.177602","url":null,"abstract":"<div><div>Neuroinflammation is a key driver in the progression of neurodegenerative diseases and central nervous system (CNS) injuries. Chrysin, a natural flavonoid, has demonstrated significant neuroprotective effects due to its anti-inflammatory, antioxidant, and anti-apoptotic properties. This scoping review systematically analyzed 29 studies published between 2005 and 2023, identified through a search of PubMed, Scopus, and Web of Science databases (yielding 1919 initial records). Chrysin mitigates neuroinflammation by inhibiting NF-κB signaling, downregulating pro-inflammatory cytokines (TNF-α, IL-6, IL-1β), and suppressing the expression of key inflammatory enzymes, including iNOS and COX-2. It also modulates critical signaling pathways, such as PI3K/Akt/mTOR and JNK, while enhancing antioxidant defenses through increased activity of enzymes like superoxide dismutase and glutathione peroxidase. Importantly, chrysin exhibits anti-apoptotic effects by regulating the expression of apoptotic markers, including the downregulation of Bax and caspase-3 and the upregulation of Bcl-2, thereby preventing neuronal cell death. These mechanisms have been validated in preclinical CNS inflammation models, including spinal cord injury, traumatic brain injury, ischemia/reperfusion injury, Parkinson's disease, and experimental autoimmune encephalomyelitis. Despite its promising therapeutic potential, limitations such as low bioavailability and the lack of comprehensive clinical studies warrant further investigation. Addressing these gaps could enhance chrysin's translational potential as a viable neuroprotective agent for managing neuroinflammatory and neurodegenerative conditions.</div></div>","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":"997 ","pages":"Article 177602"},"PeriodicalIF":4.2,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143788230","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":"Corrigendum to \"Dysregulation of serotonergic neurotransmission in Parkinson disease: A key duet\" [Eur. J. Pharmacol. 995 (2025) 177419].","authors":"Manal M Khowdiary, Hayder M Al-Kuraishy, Ali I Al-Gareeb, Ali K Albuhadily, Ahmed A Elhenawy, Ahmad O Babalghith, Mustafa M Shokr, Athanasios Alexiou, Marios Papadakis, Gaber El-Saber Batiha","doi":"10.1016/j.ejphar.2025.177540","DOIUrl":"10.1016/j.ejphar.2025.177540","url":null,"abstract":"","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":" ","pages":"177540"},"PeriodicalIF":4.2,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143794375","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":"Tomentosin mitigates the LPS induced cardiac injury by regulating Nrf-2/Nf-κβ pathway in mice","authors":"Mehmet Güvenç ,&nbsp;Tuba Aydin ,&nbsp;Tuncer Kutlu ,&nbsp;Muhammed Etyemez ,&nbsp;Cafer Tayer İşler","doi":"10.1016/j.ejphar.2025.177589","DOIUrl":"10.1016/j.ejphar.2025.177589","url":null,"abstract":"<div><div>Endotoxemic shock is a severe complication characterized by multiple organ failure, hypotension, and impaired tissue perfusion, all contributing to high morbidity and mortality. Recent studies have highlighted the anti-inflammatory and antioxidant properties of tomentosin. This study investigates the protective effects of tomentosin against lipopolysaccharide (LPS)-induced cardiac injury and elucidates its underlying mechanisms.</div><div>Mice were pre-treated with tomentosin before the LPS administration. Subsequently, cardiac injury markers, oxidative stress parameters, inflammatory mediators, and Nrf-2/NF-κB protein expression levels were analysed.</div><div>The results demonstrated that tomentosin significantly reduced Troponin and CK-MB levels, alleviated oxidative stress, and suppressed inflammatory responses. Furthermore, tomentosin inhibited NF-κB activation while enhancing Nrf-2 expression.</div><div>In conclusion, our findings suggest that tomentosin exerts cardioprotective effects by modulating the Nrf-2/NF-κB pathway, positioning it as a potential therapeutic candidate for preventing LPS-induced cardiac dysfunction.</div></div>","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":"996 ","pages":"Article 177589"},"PeriodicalIF":4.2,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143785961","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}