European journal of pharmacology最新文献

{"title":"Beta-asarone alleviated cerebral ischemia/reperfusion injury by targeting PINK1/Parkin-dependent mitophagy","authors":"Yujiao Wang ,&nbsp;Daojun Xie ,&nbsp;Shijia Ma ,&nbsp;Yuhe Wang ,&nbsp;Chengcheng Zhang ,&nbsp;Zhuyue Chen","doi":"10.1016/j.ejphar.2025.177831","DOIUrl":"10.1016/j.ejphar.2025.177831","url":null,"abstract":"<div><div>Cerebral ischemia–reperfusion injury (CIRI) describes a secondary type of brain damage that happens when blood flow is restored to brain tissue; it ranks among the primary contributors of disability and mortality. The activation of PINK1/Parkin-mediated mitophagy exerts neuroprotective effects during CIRI. Beta-asarone (β-ASA), the principal active component of traditional natural drugs such as Acori tatarinowii rhizoma and Ligusticum chuanxiong Hort, possesses anti-inflammatory, antioxidant, and autophagy-enhancing properties. However, whether β-ASA can ameliorate CIRI by regulating the PINK1/Parkin-dependent mitophagy pathway remains unclear and warrants further investigation. The purpose of this study is to explore the underlying mechanism through which β-ASA influences PINK1/Parkin-mediated mitophagy in the hippocampus following ischemia<strong>–</strong>reperfusion. In the results section, the present study examined the effects of β-ASA on middle cerebral artery occlusion/reperfusion (MCAO/R)-induced neurological deficits using the Longa test and TTC staining, rats were then treated with β-ASA (20, 40, and 80 mg/kg). The findings demonstrate that β-ASA promotes functional recovery in post-ischemic stroke, as evidenced by improved neurological function, reduced infarct volume, decreased neuronal damage, and lowered neuronal apoptosis. Furthermore, β-ASA significantly enhanced autophagy by increasing Beclin1 expression while reducing P62 and LC3-I/LC3-II expression. Additionally, β-ASA markedly activated PINK1/Parkin-mediated mitophagy. Finally, the introduction of mitophagy inhibitors was employed to clarify the relationship between autophagy and β-ASA, indicating that β-ASA promotes autophagy by activating the PINK1/Parkin signalling pathway. In conclusion, this study elucidates that β-ASA alleviates cerebral infarction, neurological impairment, and neuronal damage by targeting PINK1/Parkin-dependent mitophagy, thereby presenting a potential therapeutic strategy for CIRI.</div></div>","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":"1002 ","pages":"Article 177831"},"PeriodicalIF":4.2,"publicationDate":"2025-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144255059","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":"Therapeutic potential of flavonoids against α-synuclein aggregation in Parkinson's Disease: Integrative in silico and in vitro analysis","authors":"Fereshteh Ramezani Khorsand,&nbsp;Bahareh Dabirmanesh,&nbsp;Khosro Khajeh","doi":"10.1016/j.ejphar.2025.177829","DOIUrl":"10.1016/j.ejphar.2025.177829","url":null,"abstract":"<div><div>Amyloidogenic protein aggregation is the key factor in neurodegenerative diseases. Due to the cost-effectiveness and low side effects, attention to herbal medicines has been recently increased. Flavonoids are a group of plant compounds with high potential for reducing the accumulation of amyloidogenic proteins. This research aims to identify the most effective flavonoids for inhibiting the fibrillation of α-synuclein (α-syn). For this purpose, 98 flavonoids from different databases were selected for analysis. The pharmacokinetic properties of these flavonoids were evaluated using OSIRIS and Swiss-ADME web tools. The interaction of α-syn and flavonoids was investigated in the positions predicted via DoGSiteScorer and CASTp web servers. Subsequently, luteolin and baicalein, the flavonoids with the most negative binding energy and interaction with the amino acids of α-syn amyloidogenic regions, were selected for further <em>in vitro</em> studies. In this phase, α-syn was incubated under fibrillation conditions in the presence and absence of flavonoid treatment. Results from the thioflavin T (ThT) fluorescence assay, atomic force microscopy (AFM), and proteinase K (PK) enzymatic digestion assay showed that baicalein and luteolin significantly inhibited α-syn fibril formation. Fourier transform infrared spectroscopy (FTIR) demonstrated a decrease in β-sheet content and confirmed the inhibitory effect of baicalein and luteolin. In addition, cell culture analysis also showed that luteolin could increase the viability of SH-SY5Y cells exposed to α-syn fibrils by destabilizing toxic fibrils and converting them into non-toxic amorphous aggregates. These findings can be useful to develop flavonoid-based therapeutic strategies for synucleinopathies, such as Parkinson's disease (PD).</div></div>","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":"1002 ","pages":"Article 177829"},"PeriodicalIF":4.2,"publicationDate":"2025-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144257702","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":"Preincubation with antipsychotic drugs protects against in vitro phencyclidine-mediated spontaneous neuronal network suppression","authors":"Timo Jendrik Faustmann ,&nbsp;Stephan Theiss ,&nbsp;Philipp Görtz ,&nbsp;Christian Lange-Asschenfeldt","doi":"10.1016/j.ejphar.2025.177810","DOIUrl":"10.1016/j.ejphar.2025.177810","url":null,"abstract":"<div><div>Phencyclidine (PCP), a non-competitive N-methyl-D-aspartate receptor antagonist, is known to produce schizophrenia-like psychosis in humans, including positive and negative symptoms as well as cognitive dysfunction. Moreover, acute administration of PCP can emulate corresponding behavioral symptoms in rodents.</div><div>We investigated the effect of PCP and the possible protective potential of typical and atypical antipsychotic drugs (APDs) <em>in vitro</em> on spontaneously active neuronal networks. To this end, murine primary cortical cells were cultured on microelectrode arrays (MEAs). Concentration-response curves of PCP ranging from 0.01 to 200 μM were generated and network spike and burst rate as well as burst peak firing rate (PFR) and burst duration was measured in stable 2-min recordings. Measurements were done with and without pre-incubation with the APDs aripiprazole, clozapine, and haloperidol.</div><div>We found a concentration-dependent network activity suppression reflected by a decrease in captured spike rate and network PFR upon PCP application relative to baseline. Preexposure with any of the three APDs mediated a right-shift of the PCP concentration-response curve (spike rate, PFR). However, as assessed by their IC₅₀ values and Hill coefficients, the atypical APDs aripiprazole and clozapine exhibited a 20- to 30-fold protective potency—higher than the typical APD haloperidol (6-fold).</div><div>In summary, a disruptive network effect of PCP as well as a protection by APDs could be demonstrated in the order of potency: clozapine &gt; aripiprazole ≫ haloperidol. We propose this simple, noninvasive setup as a plausible electrophysiological model for testing current and future pharmaceuticals against schizophrenia-spectrum disorders.</div></div>","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":"1002 ","pages":"Article 177810"},"PeriodicalIF":4.2,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144247133","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":"Combined effects of gabapentin with verapamil and metoprolol on cardiovascular function of anesthetized male rats","authors":"Sarah Pribil Pardun ,&nbsp;Spencer Duff ,&nbsp;Ian Papenfus ,&nbsp;Will Bruening ,&nbsp;Yulong Li ,&nbsp;Gurudutt Pendyala ,&nbsp;Lie Gao","doi":"10.1016/j.ejphar.2025.177828","DOIUrl":"10.1016/j.ejphar.2025.177828","url":null,"abstract":"<div><div>Gabapentin (GBP), at high plasma concentrations, negatively impacts cardiovascular function, causing bradycardia, hypotension, and impaired left ventricular (LV) function in rats. This study examines the combined effects of GBP with Verapamil (Ver) or Metoprolol (Met) on cardiovascular function in anesthetized male rats and its impact on Ca²⁺ current and calmodulin (CaM) protein expression in cultured H9c2 cells. Twenty-two male Sprague Dawley rats were assigned to four groups: Saline + Ver, GBP + Ver, Saline + Met, and GBP + Met. Under isoflurane anesthesia, rats underwent ECG monitoring and LV hemodynamic and blood pressure (BP) assessment. GBP (50 mg/kg) was administered intravenously, followed by Ver (0.05–0.4 mg/kg) or Met (0.5 mg/kg). In the first experiment, Ver induced a dose-dependent reduction in BP, heart rate (HR), and maximal dP/dt, while increasing minimal dP/dt, in both saline control and GBP-treated groups with the latter group showing greater effects. In the second experiment, GBP significantly reduced BP, HR, and maximal dP/dt while increasing minimal dP/dt compared to baseline. These effects were further exacerbated by Met, leading to greater reductions in BP, HR, and maximal dP/dt, and increases in minimal dP/dt compared to Met alone. In addition, in vitro experiments demonstrated that GBP reduced Ca²⁺ current and downregulated CaM protein. These findings suggest that, at high plasma concentrations, GBP enhances the negative chronotropic, negative inotropic, and hypotensive effects of both Ver and Met, further highlighting the need for additional preclinical and clinical studies to characterize the potential drug interactions between GBP and calcium channel blockers or beta-1 blockers, particularly in patients with cardiovascular disease.</div></div>","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":"1002 ","pages":"Article 177828"},"PeriodicalIF":4.2,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144242434","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":"LRP1 at the crossroads of Parkinson's and Alzheimer's: Divergent roles in α-synuclein and amyloid pathology","authors":"Sultan M. Alshahrani ,&nbsp;Hayder M. Al-kuraishy ,&nbsp;Ali I. Al-Gareeb ,&nbsp;Ali K. Albuhadily ,&nbsp;Mustafa M. Shokr ,&nbsp;Sultan F. Kadasah ,&nbsp;Athanasios Alexiou ,&nbsp;Marios Papadakis ,&nbsp;Gaber El-Saber Batiha","doi":"10.1016/j.ejphar.2025.177830","DOIUrl":"10.1016/j.ejphar.2025.177830","url":null,"abstract":"<div><div>Parkinson's disease (PD) is the second most common neurodegenerative disease that represents the commonest movement disorder in the elderly population. PD neuropathology is due to the progressive deposition of mutant alpha synuclein (α-Syn) in the dopaminergic neurons (DNs) of the substantia nigra pars compacta (SNpc). Additionally, amyloid protein (Aβ) and tau protein, which are the hallmarks of Alzheimer's disease (AD), are also involved in PD and the development of PD-related dementia. Notably, α-Syn, Aβ, tau protein, and neuronal cholesterol metabolism are regulated by a transmembrane protein, low-density lipoprotein receptor-related protein 1 (LRP1), which is highly expressed in the SNpc and mediates the transmission and seeding of α-Syn in the brain. It has been reported that deletion of the LRP1 gene protects against the development and progression of PD. However, LRP1 has a neuroprotective effect against AD neuropathology by improving Aβ clearance across the blood-brain barrier (BBB) and enhancing tau protein proteolysis. Nevertheless, the exact role of LRP1 in PD neuropathology, mostly about α-Syn, is not completely explained. Therefore, this review aims to discuss and explain the role of LRP1 in PD and how targeting neuronal LRP1 may be helpful in the management of PD. In this review, online databases were involved by searching Scopus, Web of Science, and other search engine to detect the relationship between the expression of LRP1 and the pathogenesis of PD.</div></div>","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":"1002 ","pages":"Article 177830"},"PeriodicalIF":4.2,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144242496","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":"CYT997 Induces Apoptosis in Hypertrophic Scar Fibroblasts and Inhibits Scar Formation.","authors":"Xia Li, Fan Tian, Zhen-Yu Zhang, Jun-Jie Wu, Zheng-Dong Yuan, Feng-Lai Yuan, Jinghua Chen","doi":"10.1016/j.ejphar.2025.177815","DOIUrl":"https://doi.org/10.1016/j.ejphar.2025.177815","url":null,"abstract":"<p><p>Emerging evidence indicates that hypertrophic scars (HS) display tumor-like behaviors, characterized by excessive, rapid cellular proliferation. To investigate potential therapeutic interventions, this study focused on the effects of CYT997, a novel anti-cancer drug, on hypertrophic scar fibroblasts (HSFs). HS tissues were collected from patients and compared with normal skin samples. CYT997 decreased HSF viability in a concentration-dependent manner, with a selected concentration for further experiments. It selectively induced apoptosis in HSFs but not in normal fibroblasts, as shown by flow cytometry and fluorescence microscopy. CYT997 also reduced HSF migration, contractility, and expression of collagen I and α-smooth muscle actin (α-SMA), indicating decreased fibrosis. In a rabbit ear hypertrophic scar model, CYT997 treatment inhibited scar formation, reduced the scar elevation index, and promoted apoptosis in HSFs. It also regulated apoptosis-related proteins poly(ADP-ribose) polymerase (PARP) and caspase-3 in HSFs. These findings suggest that CYT997 has potential as a targeted therapy for hypertrophic scars by inducing apoptosis in HSFs and reducing fibrotic activity.</p>","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":" ","pages":"177815"},"PeriodicalIF":4.2,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144247130","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":"Dietary alpha-lipoic acid prevents depression-like and anxiety-like behavior under aircraft noise exposure in young adult male mice","authors":"Kangli Zhang ,&nbsp;Liyong Yan ,&nbsp;Xiaojing Lin ,&nbsp;Chenyi Li ,&nbsp;Xueqing Yi ,&nbsp;Zhongya Shi ,&nbsp;Cheng-Hsien Lin ,&nbsp;Gang Sun","doi":"10.1016/j.ejphar.2025.177834","DOIUrl":"10.1016/j.ejphar.2025.177834","url":null,"abstract":"<div><h3>Objective</h3><div>Alpha-lipoic acid (ALA) can act as a dietary supplement with antioxidant and anti-inflammatory properties and an exercise-mimetic therapy. In this study, we hypothesized that dietary supplementation with ALA would protect against aircraft noise (AN)-induced depression-like and anxiety-like behaviors and spatial memory loss in a mouse mode.</div></div><div><h3>Methods</h3><div>Mice were randomly divided into four groups. Group 1 and group 2 mice received vehicle diet plus non-AN and vehicle diet plus AN 2h daily for 6 weeks, respectively. Group 3 and group 4 mice received ALA diet plus non-AN and ALA diet plus AN 2h daily for 6 weeks, respectively. Six weeks later, neurobehavioral function, intestinal and blood-brain barrier permeability, stress reactions, and blood levels of endotoxin, pro-inflammatory cytokines, and oxidative damaged markers in the blood or other tissues were assessed for these groups of mice.</div></div><div><h3>Results</h3><div>Compared with controls, AN mice with ALA had a lesser extent of depression-like and anxiety-like behavior and spatial memory loss, exacerbated stress reactions, gut barrier disruption, endotoxemia, blood-brain barrier disruption, and inflammatory and oxidative injury to the heart, duodenum and hippocampal tissues. All the depression-like and anxiety-like behaviors, spatial memory, and causative factors that occurred during AN exposure were all significantly (P &lt; 0.01) attenuated by ALA supplementation.</div></div><div><h3>Conclusions</h3><div>These findings suggest that AN can lead to exacerbated stress reactions, endotoxemia, blood-brain barrier disruption, hippocampal inflammation, and oxidative stress, which may act as causative factors for depression-like and anxiety-like behavior and spatial memory loss. ALA, an anti-inflammatory, antioxidant, and exercise-mimetic agent, inhibited aircraft noise-induced depression-like and anxiety-like behavior in mice.</div></div>","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":"1002 ","pages":"Article 177834"},"PeriodicalIF":4.2,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144247131","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":"Glycyrrhizic acid mitigates hepatocyte steatosis and inflammation through ACE2 stabilization via dual modulation of AMPK activation and MDM2 inhibition","authors":"Longyue Zhou ,&nbsp;Yun Yi ,&nbsp;Bingqi Lin ,&nbsp;Zhenwen Qiu ,&nbsp;Chunxia Wang ,&nbsp;Yuhao Li","doi":"10.1016/j.ejphar.2025.177817","DOIUrl":"10.1016/j.ejphar.2025.177817","url":null,"abstract":"<div><div>As a hepatoprotective phytochemical derived from <em>Glycyrrhiza</em> species, glycyrrhizic acid (GA) exhibits unique dual-target therapeutic efficacy against metabolic-driven hepatic steatosis and inflammation. Building upon our previous finding that GA-mediated amelioration of murine steatohepatitis is closely associated with restoration of hepatic ACE2/Ang (1–7)/Mas axis signaling, this study was designed to identify the role of hepatocyte ACE2 both in vitro and <em>in vivo</em>, and mechanistically decipher how GA reprograms ACE2 signaling. We found that GA treatment mitigated steatosis and inflammation in LPS/free fatty acid-stimulated hepatocytes. GA reversed the downregulation of ACE2 and Mas protein expression, while it suppressed the overexpression of Ang II and sterol regulatory element-binding protein 1c proteins. Notably, the ACE2 gene silencing abolished the beneficial effects. Furthermore, GA not only reversed the downregulation of ACE2 Y781 and phosphorylated AMPKα protein levels, but also inhibited the overexpression of total and phosphorylated MDM2 proteins in both the livers of LPS/D-galactosamine-induced steatohepatitic mice and in LPS/free fatty acid-stimulated hepatocytes. The GA-induced recovery of downregulated ACE2 protein expression in hepatocytes was abolished by either the AMPKα gene silencing or MDM2 overexpression. Therefore, this study first identifies GA as an agent that ameliorates hepatocyte steatosis and inflammation through the ACE2-dependent pathway. Further, our results demonstrate that GA regulates ACE2 by targeting AMPK and MDM2. We propose that GA stabilizes ACE2 via both AMPK-mediated phosphorylation and MDM2-mediated ubiquitination. Our findings offer new insights into the molecular mechanisms underlying the hepatoprotective effects of GA.</div></div>","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":"1002 ","pages":"Article 177817"},"PeriodicalIF":4.2,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144242433","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":"IκBζ promotes acute myocardial infarction via endonuclear STAT3 deactivation","authors":"Tong Zhou ,&nbsp;Hong Hong ,&nbsp;Lu Zhang ,&nbsp;Yang Qiao ,&nbsp;Yuan Jiang ,&nbsp;Ximing Chen ,&nbsp;Zheng Dong ,&nbsp;Bo Zhang ,&nbsp;Mingyu Zhang ,&nbsp;Chaoqian Xu ,&nbsp;Rong Zhang","doi":"10.1016/j.ejphar.2025.177811","DOIUrl":"10.1016/j.ejphar.2025.177811","url":null,"abstract":"<div><div>The protein IkappaB-Zeta (IκBζ), which is a member of the IkappaB (IκB) family, has been implicated in the onset and progression of immune-mediated inflammation and cancer. However, its role in cardiovascular disease remains totally unexplored. We employed advanced molecular techniques to investigate the upregulation of IκBζ protein in mouse models of acute myocardial infarction (AMI) and cellular oxygen-glucose deprivation (OGD), with a focus on nuclear localization. Our results indicate that inhibiting IκBζ protein expression both <em>in vivo</em> and <em>in vitro</em> can reduce cardiomyocyte apoptosis and alleviate cardiac hypoxic injury. Mechanistically, IκBζ influences cardiomyocyte apoptosis by binding to and regulating the activity of the intracellular signal transduction factor and transcriptional activator (STAT3). Upon AMI occurrence, the janus kinase 2-signal transducer and activator of transcription 3 (JAK2/STAT3) signaling pathway is activated, leading to STAT3 phosphorylation and its subsequent translocation into the nucleus. It interacts with activated IκBζ in the nucleus, resulting in decreased STAT3 activity and exacerbating cardiomyocyte apoptosis. Treatment with a STAT3-specific agonist mitigated the pro-apoptotic effects caused by IκBζ overexpression. In conclusion, our study describes for the first time the molecular link in IκBζ and STAT3 and reveals that pro-apoptotic IκBζ plays a crucial role in AMI pathogenesis by downregulating STAT3 activity. These findings suggest that targeting IκBζ may provide a foundation for developing novel therapeutic strategies for the prevention and treatment of myocardial infarction.</div></div>","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":"1002 ","pages":"Article 177811"},"PeriodicalIF":4.2,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144247132","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 liver-gut axis perspective: Exploring the pathogenesis of fatty liver","authors":"Zonghui Yang ,&nbsp;Jinbao Zhang ,&nbsp;Xiaona Liu ,&nbsp;Honggang Chen ,&nbsp;Haijing Duan ,&nbsp;Qian Wang ,&nbsp;Wenlong Zhao ,&nbsp;Ling Jin","doi":"10.1016/j.ejphar.2025.177822","DOIUrl":"10.1016/j.ejphar.2025.177822","url":null,"abstract":"<div><div>Fatty liver is one of the most common chronic liver diseases globally, affecting approximately a quarter of the world's population. It poses a significant burden on global health. Its pathogenesis is highly complex. In recent years, increasing attention has been paid to exploring the pathogenesis of fatty liver from the perspective of the liver-gut axis. We first discuss the liver-gut axis in fatty liver, detailing the bidirectional communication between the liver and the intestines. Specifically, the liver releases primary bile acids and numerous bioactive mediators into the biliary tract and systemic circulation, which then interact with the intestine. Conversely, intestinal microorganisms and their metabolites are transported to the liver via the portal vein, thereby influencing liver function. In addition, the interactions between intestinal microbes, the host's immune system, and various soluble factors are described, including their contributions to fatty liver development. Second, we describe the mediators of communication between the intestine and the liver in the pathological state of fatty liver, focusing on three key substances: endotoxins, bile acids, and short-chain fatty acids. Third, we summarize the emerging treatments derived from the liver-gut axis in fatty liver, highlighting frontier findings that may lead to the development of novel therapies. Finally, we offer suggestions for future research directions. We hope that future studies will propose better research strategies for the interaction of the liver-gut axis to promote the development of new treatment strategies and the discovery of precise therapeutic targets for fatty liver.</div></div>","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":"1002 ","pages":"Article 177822"},"PeriodicalIF":4.2,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144247134","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}