European journal of pharmacology最新文献

{"title":"Single-cell omics: moving towards a new era in ischemic stroke research","authors":"Jieqiong Zeng ,&nbsp;Huifen Zhou ,&nbsp;Haitong Wan ,&nbsp;Jiehong Yang","doi":"10.1016/j.ejphar.2025.177725","DOIUrl":"10.1016/j.ejphar.2025.177725","url":null,"abstract":"<div><div>Ischemic stroke (IS) is a highly complex and heterogeneous disease involving multiple pathophysiological events. A better understanding of the pathophysiology of IS will enhance preventive, diagnostic and therapeutic strategies. Despite significant advances in modern medicine, the molecular mechanisms of IS are still largely unknown. The high-throughput omics approach opens new avenues for identifying IS biomarkers and elucidating disease pathogenesis mechanisms. Single-cell omics enables a more thorough and in-depth analysis of the cellular interactions and properties in IS. This will lead to a better understanding of the onset, treatment and prognosis of IS. In this paper, we first reviewed the disease signatures and mechanisms research of IS. Subsequently, the use of single-cell omics to comprehend the mechanisms of IS was discussed, along with some recent developments in the field. To further delineate the upstream pathogenic alterations and downstream molecular impacts of IS, we also discussed the current use of machine learning approaches to single-cell omics data analysis. Particularly, single-cell omics is being used to inform risk assessment, early patient diagnosis and treatment strategies, and their potential impact on precision medicine. Thus, we summarized the role of single-cell omics in precision medicine. Despite the relative youth of the field, the development of single-cell omics promises to provide a powerful tool for elucidating the pathogenesis of IS.</div></div>","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":"1000 ","pages":"Article 177725"},"PeriodicalIF":4.2,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143948425","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":"In vivo and In vitro Crosstalk Among CBD, Aβ, and endocannabinoid system enzymes and receptors","authors":"Fangyuan Duan ,&nbsp;Dan Xiao ,&nbsp;Jiayu Wang ,&nbsp;Runze Li ,&nbsp;Xiaoyue Si ,&nbsp;Weihong Lu","doi":"10.1016/j.ejphar.2025.177720","DOIUrl":"10.1016/j.ejphar.2025.177720","url":null,"abstract":"<div><div>Cannabidiol (CBD), a non-psychotropic compound derived from <em>Cannabis sativa</em>, has garnered attention as a potential therapeutic agent for various neurodegenerative diseases, including Alzheimer's disease (AD). Despite growing interest, additional research is required to clarify the specific mechanisms by which CBD influences the pathological accumulation of β-amyloid (Aβ) associated with AD. Moreover, the interactions between CBD and the endocannabinoid system (ECS), both in the presence and absence of Aβ expression, remain a subject of active investigation. Elucidating these mechanisms may provide valuable insights for advancing both our understanding and the development of targeted interventions in neurodegenerative disease management.</div><div>Using a multifaceted approach that integrates pharmacological interventions, immunofluorescence imaging, flow cytometry, and biochemical assays, we examined the effects of CBD on Aβ40 and Aβ42. Additionally, we analyzed the modulation of cannabinoid receptor 1(CB1 receptor) and fatty acid amide hydrolase (FAAH) in the presence or absence of Aβ expression, uncovering the intricate regulatory mechanisms of CBD. Our findings indicate a nuanced response to CBD; while it may produce side effects in non-pathological cells, it demonstrates an ability to induce autophagy and apoptosis in Aβ-expressing cells via the activation of the Microtubule-associated protein 1 light chain 3 B(LC3B) and Caspase-3 pathways. Furthermore, our investigation into <em>faah-1</em> involvement highlighted its role in alleviating pharyngeal dysfunction and counteracting weight loss in Aβ-expressing <em>Caenorhabditis eleg</em>ans(<em>C. elegans)</em> strains. These insights advance our understanding of CBD's therapeutic potential in addressing neurodegenerative pathologies.</div></div>","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":"1000 ","pages":"Article 177720"},"PeriodicalIF":4.2,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143991393","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":"Eating a high fat/high carbohydrate diet enhances morphine tolerance, while eating a ketogenic diet mitigates morphine withdrawal in male rats","authors":"Nina M. Beltran ,&nbsp;Leslie L. Sullivan ,&nbsp;Gabriela M. Naime ,&nbsp;Vanessa Minervini ,&nbsp;Katherine M. Serafine","doi":"10.1016/j.ejphar.2025.177709","DOIUrl":"10.1016/j.ejphar.2025.177709","url":null,"abstract":"<div><div>Obesity is associated with greater prescription rates of pain-relieving drugs (i.e., opioids). However, it is not known if opioid sensitivity is altered by diet, in particular with regard to fat and carbohydrate consumption. While eating a high fat/high carbohydrate diet leads to weight gain, a high fat/low carbohydrate diet (i.e., a ketogenic diet) leads to weight loss. In this report, male Sprague-Dawley rats (<em>n</em> = 7–8/dietary group) ate either a standard, high fat/high carbohydrate, or ketogenic diet. Morphine-induced antinociception was evaluated using the warm water tail withdrawal procedure following saline or cumulative doses of morphine (0.32–56 mg/kg; i.p.). After acute morphine testing, rats were administered morphine twice-daily, increasing in quarter log doses every 3 days (3.2–56 mg/kg; i.p) for 19 days to induce dependence and evaluate tolerance. Next, naltrexone-precipitated withdrawal was evaluated. Based on previous data, it was hypothesized that the magnitude of tolerance would be greater from eating a high fat/high carbohydrate diet, while withdrawal would be less severe for rats eating a ketogenic diet. Antinociception induced by acute doses of morphine was comparable among groups, regardless of diet. Further, rats in all groups developed tolerance to morphine; however, the magnitude of tolerance was greater for rats eating the high fat/high carbohydrate diet as compared to those eating a ketogenic diet. Rats eating a ketogenic diet displayed less severe withdrawal than rats in other groups. These results suggest that dietary intake can impact morphine sensitivity in ways that might be relevant for chronic pain management and opioid use disorder.</div></div>","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":"1000 ","pages":"Article 177709"},"PeriodicalIF":4.2,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143980360","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":"Delirium risk associated with esketamine, sevoflurane, propofol, and dexmedetomidine: A real-world study based on the FDA adverse event reporting system","authors":"Yichun Shuai,&nbsp;Yan Liu,&nbsp;Xiahong Yang,&nbsp;Qiaoqian Wan,&nbsp;Jie Zhao,&nbsp;Xin Wang","doi":"10.1016/j.ejphar.2025.177723","DOIUrl":"10.1016/j.ejphar.2025.177723","url":null,"abstract":"<div><h3>Objective</h3><div>Delirium is a serious postoperative complication, increasingly recognized for its heightened risk following the use of sedative drugs. This study aimed to assess the relationship of esketamine, sevoflurane, propofol, and dexmedetomidine with the risk of delirium.</div></div><div><h3>Methods</h3><div>Data were obtained from the FDA Adverse Event Reporting System (FAERS) database covering the period from the first quarter of 2004 to the second quarter of 2024. Cases of delirium associated with these medications were identified using preferred terms (PTs) defined by the Medical Dictionary for Regulatory Activities (MedDRA 20.0). Disproportionality analyses employed reported odds ratios (ROR) and multiple gamma-Poisson shrinkage (MGPS), while logistic regression assessed the effects of age and sex on the risk of delirium.</div></div><div><h3>Results</h3><div>A total of 21,433,114 adverse events (AEs) were recorded in the FAERS database, including 16 cases of delirium associated with esketamine, 189 with propofol, 90 with sevoflurane, and 103 with dexmedetomidine. Propofol (ROR: 5.44, EBGM05: 4.8), sevoflurane (ROR: 9.9, EBGM05: 8.26), and dexmedetomidine (ROR: 21.1, EBGM05: 17.67) were significantly associated with the delirium risk, whereas esketamine (ROR: 1.45, EBGM05: 0.96) did not show a significant association. Age was identified as a significant risk factor for delirium, particularly in patients aged 55 years and older.</div></div><div><h3>Conclusion</h3><div>The findings indicate a significant correlation between propofol, sevoflurane, and dexmedetomidine and the risk of delirium, whereas esketamine does not appear to have a significant association with delirium. Future studies should further explore drug administration and dosage effects on delirium risk to improve clinical safety.</div></div>","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":"1000 ","pages":"Article 177723"},"PeriodicalIF":4.2,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143989177","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 the novel σ1 receptor ligand (S)-L1 on brain endothelial cells and cerebrovascular reactivity challenged by ischemia","authors":"Szilvia Kecskés ,&nbsp;Mária Mészáros ,&nbsp;Szabolcs Dvorácskó ,&nbsp;Írisz Szabó ,&nbsp;Gergő Porkoláb ,&nbsp;Lilla Barna ,&nbsp;András Harazin ,&nbsp;Anikó Szecskó ,&nbsp;Ákos Menyhárt ,&nbsp;Ferenc Bari ,&nbsp;Mária A. Deli ,&nbsp;Botond Penke ,&nbsp;Eszter Farkas ,&nbsp;Szilvia Veszelka","doi":"10.1016/j.ejphar.2025.177724","DOIUrl":"10.1016/j.ejphar.2025.177724","url":null,"abstract":"<div><div>Intracellular sigma-1 receptors (σ₁ receptors) have a versatile function through the regulation of lipid rafts, neuroreceptors and ion channels, and can influence signal transduction and neuronal plasticity. Since decreased activity of σ₁ receptors is a common pathological feature in the early stages of many neurological diseases, σ₁ receptor agonists may represent a promising therapeutic tool for the treatment of these disorders. In this study, we aimed to comprehensively investigate the potential protective effects of the novel synthetic σ₁ receptor agonist (S)-L1 against endothelial endoplasmic reticulum (ER) stress and cerebral ischemia. In binding affinity experiments, we showed that (S)-L1 has a high affinity and selectivity for σ₁ receptor with virtually no affinity for any of the other receptors tested. Next, (S)-L1 exerted protection against endoplasmic reticulum stress in human brain endothelial cells, consistent with the localization of σ₁ receptors in endothelial cells. Furthermore, (S)-L1 penetration was demonstrated across the cell culture model of the blood-brain barrier, providing a rationale for neuronal action in addition to endothelial protection. Finally, (S)-L1 inhibited spreading depolarization, suppressed apoptosis and rescued astrocytes in a rat model of cerebral ischemia. Based on our results, (S)-L1 exerts a protective effect on both brain endothelial cells and neural tissue. Moreover, since these experiments revealed no affinity for serotonergic receptors, the compound holds promise as an adjuvant therapy for the treatment of cerebrovascular disease without potential psychedelic side effects.</div></div>","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":"1000 ","pages":"Article 177724"},"PeriodicalIF":4.2,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143984376","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 butyrate against heat Stress–Induced intestinal damage, systemic inflammation, and multiple organ Dysfunction: Insights from in vitro and in vivo experiments","authors":"Hung-Yen Ke ,&nbsp;Ming-Hua Chen ,&nbsp;Cheng-Ming Tsao ,&nbsp;Hiong-Ping Hii ,&nbsp;Chia-Wen Kuo ,&nbsp;Shuk-Man Ka ,&nbsp;Chin-Chen Wu ,&nbsp;Chih-Chin Shih","doi":"10.1016/j.ejphar.2025.177710","DOIUrl":"10.1016/j.ejphar.2025.177710","url":null,"abstract":"<div><div>Global warming is a major risk factor for life-threatening heat stroke (HS). Systemic inflammation plays a key role in the pathophysiology of HS, substantially affecting clinical outcomes. Reduced intestinal blood flow during HS causes ischemia-reperfusion injury, compromising the intestinal barrier and triggering systemic inflammation and organ damage. Butyrate, a short-chain fatty acid, plays a multifaceted role in maintaining intestinal health, inhibiting inflammation, and alleviating oxidative stress. Therefore, this study aimed to evaluate butyrate's therapeutic potential against HS and explored the mechanisms underlying its protective effects. Male Wistar rats were divided into 4 groups: control, control + butyrate, HS, and HS + butyrate. Hemodynamic changes, biochemical parameters, coagulation markers, cytokine levels, polymorphonuclear neutrophil infiltration, and survival rates were analyzed. Additionally, ileal samples (from rats) and LS174T cells were used to investigate the effect of butyrate on intestinal function. Heat stress induced cytotoxicity; reduced transepithelial resistance in intestinal goblet cells; and triggered intestinal inflammation, oxidative stress, and apoptosis in HS rats. These rats exhibited systemic inflammation, hypotension, tachycardia, coagulopathy, multiple organ dysfunction, and mortality. Butyrate treatment reduced cytotoxicity and improved transepithelial resistance in LS174T cells. Butyrate also reduced intestinal heat stress, inflammation, oxidative stress, and apoptosis, as well as systemic inflammation in HS rats. Furthermore, butyrate ameliorated hypotension, tachycardia, coagulopathy, and multiple organ dysfunction and increased survival in HS rats. These findings indicate that butyrate is a promising intervention for mitigating heat stress–induced intestinal damage, systemic inflammation, and multiple organ dysfunction.</div></div>","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":"999 ","pages":"Article 177710"},"PeriodicalIF":4.2,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143936857","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":"OpiCa1 reduces inflammation and ROS levels counteracting heat stress-induced cardiac injury","authors":"Zhixiao Yang ,&nbsp;Xiaoyu Hua ,&nbsp;Fei Wang ,&nbsp;Yi Wang ,&nbsp;Xiaochuan Hou ,&nbsp;Fengling Yang ,&nbsp;XiaoXiao Chen ,&nbsp;Tianwen Liu ,&nbsp;Xiaofen Ma ,&nbsp;Héctor H. Valdivia ,&nbsp;Liang Xiao ,&nbsp;Baojing Li","doi":"10.1016/j.ejphar.2025.177711","DOIUrl":"10.1016/j.ejphar.2025.177711","url":null,"abstract":"<div><div>Heat stress exacerbates heart disease by increasing myocardial workload, and long-term exposure to high temperatures elevates cardiovascular risks. As a natural cell-penetrating peptide, OpiCa1 can rapidly bind to ryanodine receptors (RyRs), inducing a semi-open conformation and triggering calcium release. We explored OpiCa1's protective role against heat stress at 42 °C using cell viability assays, transcriptomics, and whole animal studies. Experiments showed that OpiCa1 treatment in heat-stressed H9C2 cells significantly reduced ROS, apoptosis, and inflammatory factors while increasing cell survival. OpiCa1 binds to RyRs, inducing a subconductive state and consequently restoring mitochondrial calcium homeostasis. It inhibits FOS-mediated apoptosis via modulation of the Bax/Bcl-2 ratio and suppresses inflammatory responses by regulating MAPK and PI3K signaling pathways. In heat-stressed mice, OpiCa1 significantly mitigated cardiac injury, reduced the expression levels of IL-1α and IL-6, and improved tissue integrity. Our findings reveal OpiCa1's dual function in mitigating oxidative stress and inflammation via critical apoptotic and signaling pathways, thereby presenting a promising therapeutic approach for heat-related cardiovascular disorders.</div></div>","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":"999 ","pages":"Article 177711"},"PeriodicalIF":4.2,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143931461","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":"Dihydromyricetin restores mucus hypersecretion in Air–Liquid interface cultures in COPD by targeting the SRC-MAPK signaling pathway","authors":"Yiqi Liu ,&nbsp;Nan Di ,&nbsp;Changjiang Li ,&nbsp;Yachao Cui ,&nbsp;Jinlan He ,&nbsp;Liping Wei","doi":"10.1016/j.ejphar.2025.177703","DOIUrl":"10.1016/j.ejphar.2025.177703","url":null,"abstract":"<div><div>Chronic obstructive pulmonary disease (COPD) is a heterogeneous condition characterized by chronic respiratory symptoms due to bronchitis and emphysema, often leading to persistent airflow obstruction. Dihydromyricetin (DHM), a Garcinia cambogia extract, exhibited anti-inflammatory, antitumor, and antioxidant effects without significant toxicity to normal cells in vitro and <em>in vivo</em>. This study aimed to investigate the effect of DHM on mucus hypersecretion in air–liquid interface (ALI) cultures in COPD and to explore the underlying mechanism. Bronchial epithelial cells from five COPD patients and five Non-COPD subjects were collected by bronchoscopy at ALI. ALI cultures from COPD and Non-COPD subjects, as well as airway organoids, were differentiated for 2 weeks subsequently treated with DHM (50 μM) for an additional 2 weeks. The potential molecular mechanisms of DHM were investigated using network pharmacology analysis and molecular docking techniques. DHM reduced mucus hypersecretion and increased cilia number in ALI cultures (Average fold change = 6.52, <em>P</em> = 0.0033; average fold change = 11.56, <em>P</em> = 0.0011) and airway organoids (average fold change = 1.68, <em>P</em> = 0.0096; average fold change = 1.60, <em>P</em> = 0.0130) from COPD patients. Network pharmacology analysis, supported by experimental validation, confirmed that DHM alleviated COPD-related mucus hypersecretion and improved ciliary morphology by binding to SRC and regulating autophagy-related proteins and the MAPK signaling pathway. These findings suggest that DHM could be a potential therapeutic agent for preventing mucus hypersecretion in COPD. This study is the first to combine network pharmacology analysis to investigate the mechanism of DHM in alleviating COPD-associated mucus hypersecretion.</div></div>","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":"1000 ","pages":"Article 177703"},"PeriodicalIF":4.2,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143936973","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":"Involvement of glucagon-like peptide-1 receptor in fisetin tetramethyl ether-enhanced insulin secretion in MIN6 cells","authors":"Kazunori Hashimoto ,&nbsp;Chihiro Ito ,&nbsp;Eka Takahashi ,&nbsp;Rico Nishio ,&nbsp;Ryoga Tsurigami ,&nbsp;Naoto Kato ,&nbsp;Satsuki Miyazaki ,&nbsp;Jun-ichi Miyazaki ,&nbsp;Motoyuki Shimizu ,&nbsp;Masashi Kato ,&nbsp;Hugh T.-W. Tan ,&nbsp;Tomiyasu Murata","doi":"10.1016/j.ejphar.2025.177722","DOIUrl":"10.1016/j.ejphar.2025.177722","url":null,"abstract":"<div><h3>Background</h3><div><em>Pongamia pinnata</em> (L.) Pierre, long used as a traditional medicine to treat diabetes and metabolic disorders, shows an insulinotropic effect.</div></div><div><h3>Objective</h3><div>This study aimed to determine the insulinotropic property and underlying mechanism of a constituent of <em>Pongamia pinnata</em>, fisetin tetramethyl ether (FTM).</div></div><div><h3>Methods</h3><div>The insulinotropic property of FTM was investigated using pancreatic beta cell line MIN6, while secreted insulin and residual insulin were detected by an insulin assay. Furthermore, the underlying mechanism was examined with use of an ATP assay, Ca²⁺ flux assay, and immunoblot analysis, as well as the insulin assay with pharmacological inhibitors.</div></div><div><h3>Results</h3><div>FTM increased insulin secretion in a dose-dependent manner. In addition, 10 mM or more of glucose increased insulin secretion regardless of the presence of FTM. Nimodipine, a voltage-dependent Ca channel antagonist, completely eliminated insulin secretion induced by glucose and FTM. However, FTM treatment had minimal effects on ATP and intracellular Ca²⁺ levels, suggesting its enhancement of glucose-stimulated insulin secretion (GSIS) independent of glucose metabolism. Additionally, a newly developed glucagon-like peptide-1 (GLP-1) receptor antagonist, VU0650991, reduced FTM-enhanced GSIS. Moreover, FTM-enhanced GSIS was reduced by barbadin, an inhibitor of the β-arrestins-mediated signaling pathway, as well as GSK215, a degrader of focal adhesion kinase (FAK), though not by HJC0350, an inhibitor of exchange protein activated by cAMP 2 involved in insulin granule exocytosis.</div></div><div><h3>Conclusion</h3><div>The GLP-1 receptor-β-arrestins/FAK pathway is involved in FTM-enhanced GSIS. This study showed that FTM, a constituent of <em>Pongamia pinnata</em>, is an insulinotropic phytochemical possessing biased GLP-1 receptor agonistic potential.</div></div>","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":"1000 ","pages":"Article 177722"},"PeriodicalIF":4.2,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143993248","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":"Caffeine plays a prevention role in stress-induced depression by modulating gut-brain axis function","authors":"Wentao Wu ,&nbsp;Jiaolin Wang ,&nbsp;Jianjun Chen ,&nbsp;Jing Xie ,&nbsp;Ke Xu ,&nbsp;Yi Ren ,&nbsp;Qi Zhong ,&nbsp;Fei He ,&nbsp;Ying Wang ,&nbsp;Peng Xie","doi":"10.1016/j.ejphar.2025.177721","DOIUrl":"10.1016/j.ejphar.2025.177721","url":null,"abstract":"<div><h3>Background</h3><div>Caffeine intake is inversely associated with depression in epidemiological studies and can impact gut microbiota. Considering the close relationship between depression and gut microbiota, we conducted this study to investigate whether prophylactic caffeine use could influence the development of depression by affecting gut-brain axis.</div></div><div><h3>Methods</h3><div>Male C57BL/6J mice were randomly divided into three groups: a control group, one group receiving chronic unpredictable stress (CUS) as CUS group, and one group receiving CUS after intraperitoneal injection with caffeine (CAF) as CAF group. Depressive- and anxiety-like behaviors were assessed, and gut-brain axis related molecules were examined.</div></div><div><h3>Results</h3><div>Compared to control group, CUS group had significantly lower body weight, sucrose preference, center distance (%) and higher immobility time; however, the values of these indexes were similar between control group and CAF group. Furthermore, the significantly decreased intestinal barrier integrity-related factors (Zonula Occludens-1 (ZO-1), claudin-1 and Mucin2 (MUC2)) in CUS were not observed in CAF group; and the altered levels of two inflammation factors in plasma (lipopolysaccharide (LPS) and NOD-like receptor thermal protein domain-associated protein 3 (NLRP3)) and four inflammation-related factors in hippocampus (tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), adenylyl cyclase (AC) and brain-derived neurotrophic factor (BDNF)) in CUS group were not observed in CAF group. In addition, we found that six differential genera were identified between control group and CUS group, but not between control group and CAF group; and sucrose preference were significantly correlated with five of these six differential genera.</div></div><div><h3>Conclusions</h3><div>The results suggested that early caffeine intervention might prevent depression by regulating gut microbiota, intestinal barrier integrity and neuroinflammation.</div></div>","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":"1000 ","pages":"Article 177721"},"PeriodicalIF":4.2,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143942563","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}