European journal of pharmacology最新文献

{"title":"Activation of the Nrf2 pathway by a novel bipyrazole compound mitigates doxorubicin-induced cardiotoxicity in Wistar albino rats","authors":"Abdelrahim Alqudah ,&nbsp;Esam Qnais ,&nbsp;Yousra Bseiso ,&nbsp;Sireen Abdul Rahim Shilbayeh ,&nbsp;Alaa A.A. Aljabali ,&nbsp;Omar Gammoh","doi":"10.1016/j.ejphar.2025.177731","DOIUrl":"10.1016/j.ejphar.2025.177731","url":null,"abstract":"<div><h3>Background</h3><div>Doxorubicin (DOX) clinical utility is limited by its dose-dependent cardiotoxicity. This study aimed to evaluate the cardioprotective potential of 2′,3,3,5′-Tetramethyl-4′-nitro-2′H-1,3′-bipyrazole (TMNB) in a rat model of DOX-induced cardiac injury.</div></div><div><h3>Methods</h3><div>Rats were divided into control, DOX, TMNB, and TMNB + DOX groups. TMNB was administered for 14 days. A single dose of DOX was given on day 7. Serum, oxidative stress, cytokines, apoptosis markers, and Nrf2 pathway gene expression were assessed. One-way ANOVA followed by Tukey's post-hoc test were used.</div></div><div><h3>Results</h3><div>TMNB pretreatment reduced CK-MB and LDH levels by 42.9 % and 50 %, respectively (Cohen's d &gt; 6.4, <em>p</em> &lt; 0.001). Histologically, TMNB significantly reduced myocardial damage (d = 6.63). MDA levels declined by 45.1 % in TMNB-treated rats (d = 7.18), while antioxidant enzymes SOD and CAT increased by 99.4 % and 74.1 %, respectively (<em>p</em> &lt; 0.001). TMNB restored GSH and GPx-1 levels, reversing DOX-induced oxidative depletion (all d &gt; 4.7). Pro-inflammatory cytokines TNF-α and IL-1β were reduced with TMNB pretreatment by over 40 % (d &gt; 9.3, <em>p</em> &lt; 0.001). Similarly, TMNB significantly downregulated NF-κB gene expression (d = 9.46). Caspase-3 and Bax were reduced by 44.9 % and 65.5 %, respectively (<em>p</em> &lt; 0.001), while Bcl-2 expression was restored. TUNEL staining confirmed reduced apoptosis (d = 11.20). TMNB increased Nrf2, HO-1, and NQO1 expression (Nrf2 d = 8.21) while decreasing Keap1 (<em>p</em> &lt; 0.0001).</div></div><div><h3>Conclusion</h3><div>TMNB significantly mitigates DOX-induced cardiotoxicity likely via Nrf2 pathway activation. These findings support TMNB's potential as a cardioprotective adjunct during chemotherapy, warranting further investigation in chronic and clinical models.</div></div>","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":"1000 ","pages":"Article 177731"},"PeriodicalIF":4.2,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144068667","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":"Estradiol replacement enhances sweet taste preference in ovariectomized Rats: Interaction with energy intake regulation","authors":"Natsumi Kosugi ,&nbsp;Konomi Kanamori ,&nbsp;Sayaka Kondo ,&nbsp;Aoi Takahashi ,&nbsp;Nanako Sakagawa ,&nbsp;Mio Nishimaki ,&nbsp;Keiko Morimoto ,&nbsp;Akira Takamata","doi":"10.1016/j.ejphar.2025.177719","DOIUrl":"10.1016/j.ejphar.2025.177719","url":null,"abstract":"<div><div>Estrogens exert anorectic and anti-obesity effects via homeostatic regulation. However, their role in hedonic ingestive behavior, particularly in sweet taste preference, remains unclear. We examined the effects of estradiol replacement on the intake of sweetened solutions, water, and total energy in ovariectomized rats with concurrent access to sweetened solutions, water, and a standard rodent chow. Compared with the non-replaced (E2 (−)) group, the estradiol-replaced (E2 (+)) group exhibited a higher intake of various sweetened solutions, including those containing non-caloric artificial sweeteners and natural sugars. Food intake was lower in the E2 (+) group than in the E2 (−) group. Total energy intake was lower in the E2 (+) group than in the E2 (−) group when rats consumed water, sucralose, and fructose, but not when rats consumed glucose or sucrose. To explore the involvement of μ-opioid receptors in the estrogen-induced enhancement of sucrose intake, we chronically infused naltrexone (NTX), a partial μ-opioid receptor antagonist. NTX attenuated sucrose intake in the E2 (+) group but not in the E2 (−) group. By contrast, NTX reduced food intake in the E2 (−) group. Additionally, c-Fos expression in the nucleus accumbens shell was attenuated by NTX in the E2 (+) group during the short-term sucrose preference test. These findings suggest that estrogen enhances sweet taste preference and that available palatable glucose or sucrose diminishes the estrogen-induced attenuation of homeostatic energy intake. Moreover, μ-opioid receptors possibly play a role in the estrogen-induced enhancement of hedonic sweet taste preference, while they are involved in the enhancement of homeostatic food/energy intake in the absence of estrogen.</div></div>","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":"1000 ","pages":"Article 177719"},"PeriodicalIF":4.2,"publicationDate":"2025-05-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143977698","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":"Menstrual blood and endometrial mesenchymal stem/stromal cells: A frontier in regenerative medicine and cancer therapy","authors":"Maryam Rahnama ,&nbsp;Navid Ghasemzadeh ,&nbsp;Zeinab Latifi ,&nbsp;Fatemeh Kheradmand ,&nbsp;Fariba Abbasi Koukia ,&nbsp;Sharun Khan ,&nbsp;Ali Golchin","doi":"10.1016/j.ejphar.2025.177726","DOIUrl":"10.1016/j.ejphar.2025.177726","url":null,"abstract":"<div><div>The acquisition of suitable stem cell sources is a significant issue in regenerative medicine. There has been considerable interest in utilizing mesenchymal stem cells (MSCs) derived from endometrial and menstrual blood as a promising resource of MSCs, owing to their unique biochemical properties and prospective use in clinical therapies. This population of stem cells has distinct characteristics in terms of immunophenotype, proliferation rate, and differentiation capacity. A notable characteristic of these stem cells is their capacity to develop into mesodermal lineages, highlighting their regenerative capability. Moreover, the presence of certain surface markers facilitates the augmentation of clonogenic endometrial MSCs. Their distinctive characteristics, along with their swift multiplication ability, underscore their significant promise for therapeutic applicability in regenerative medicine and cell-based treatments. Current investigations are examining possible usage of diverse stem cell resources in the treatment of inflammatory diseases and perhaps intractable illnesses like Parkinson's disease, utilizing their immunomodulatory properties. This review aims to analyze stem cell-related research that has utilized endometrial and menstrual blood-derived MSCs (enMSCs and MenSCs) with a special focus on their clinical application. We will explore the existing evidence about the therapeutic potential for these stem cells across many medical diseases and address the obstacles and prospective trajectories in this domain. Additionally, we will study the unique properties of enMSCs and MenSCs that make them promising candidates for regenerative medicine.</div></div>","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":"1000 ","pages":"Article 177726"},"PeriodicalIF":4.2,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143990458","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":"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}