European journal of pharmacology最新文献

{"title":"Visceral adipose tissue regulatory T cells: A potential new target for treating atherosclerosis","authors":"Shanshan Huang ,&nbsp;Fayin Huang ,&nbsp;Chunmei Yi ,&nbsp;Wenlan Zhang ,&nbsp;Lin Guo ,&nbsp;Tong Xia ,&nbsp;Yunong Chen ,&nbsp;Yumou Yang ,&nbsp;Weiye Tian ,&nbsp;Huhu Li ,&nbsp;Bin Yu ,&nbsp;Xiaoli Pang","doi":"10.1016/j.ejphar.2025.177998","DOIUrl":"10.1016/j.ejphar.2025.177998","url":null,"abstract":"<div><div>Atherosclerosis (AS) is the primary potential contributor to cardiovascular disease. Recent studies have demonstrated that obesity (OB)-induced visceral adipose tissue (VAT) inflammation is closely related to AS. This VAT inflammation can cause excessive proinflammatory cytokines and adipokines to enter the blood circulation, resulting in an accumulation of immune cells and proinflammatory cytokines within the arterial wall, thereby leading to vascular dysfunction and facilitating the formation of AS. Studies in animal models suggest that regulatory T cells (Tregs) present in VAT have the function of inhibiting VAT inflammation and improving metabolic disorders, thereby reducing the risk factors that induce AS. However, the underlying mechanism remains unclear. In this review, we summarize the potential mechanisms by which VAT-Treg regulate VAT inflammation, as well as relevant methods and drugs to enhance Tregs. This aims to provide a reference for assisting in the treatment of AS.</div></div>","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":"1004 ","pages":"Article 177998"},"PeriodicalIF":4.7,"publicationDate":"2025-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144729035","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":"Efficacy and safety of adjunctive intra-arterial thrombolysis after successful recanalization in patients with large vessel occlusion acute ischemic stroke: A systematic review and meta-analysis","authors":"Laila Shalabi ,&nbsp;Ahmed Ibrahim ,&nbsp;Sofian Zreigh ,&nbsp;Abdelrahman M. Tawfik ,&nbsp;Mohamed Rifai ,&nbsp;Shahed Shalabi ,&nbsp;Khayri Karban ,&nbsp;Ibrahim Elsabbagh ,&nbsp;Bahaa Shat ,&nbsp;Amr Ehab El-Qushayri ,&nbsp;Raheel Ahmed","doi":"10.1016/j.ejphar.2025.178000","DOIUrl":"10.1016/j.ejphar.2025.178000","url":null,"abstract":"<div><h3>Background</h3><div>While endovascular thrombectomy (EVT) achieves recanalization in acute large vessel occlusion (LVO) stroke, residual or recurrent distal emboli can undermine clinical outcomes. This meta-analysis examines whether adjunctive intra-arterial thrombolysis (IAT) administered post-EVT improves therapeutic efficacy without compromising safety.</div></div><div><h3>Methods</h3><div>A systematic search of PubMed, Scopus, Cochrane Library, and Web of Science (up to May 25, 2025) was conducted to identify randomized controlled trials (RCTs), comparing adjuvant intra-arterial thrombolysis to EVT alone in patients with large vessel occlusion undergoing successful EVT. Statistical analysis was performed using RStudio (v4.4.2) with a random-effects model.</div></div><div><h3>Results</h3><div>Our meta-analysis of four RCTs (1375 patients) demonstrated that adjunctive IAT significantly increased the probability of excellent functional outcome (modified Rankin Scale 0–1) at 90 days (RR 1.16; 95 % CI 1.03–1.31; P = 0.01) and reduced neurological deficit NIHSS scores (MD, −0.75; 95 % CI, −1.4 to −0.10; P = 0.02) compared to EVT alone. No significant differences were observed for 90-day mortality (RR: 0.94, 95 % CI: 0.76–1.17; P = 0.57). Furthermore, the analysis showed a statistically significant, albeit marginal, increase in radiological intracranial hemorrhage (RR: 1.26, 95 % CI: 1.00–1.58; P = 0.045), without a corresponding increase in symptomatic intracranial hemorrhage or systemic bleeding.</div></div><div><h3>Conclusion</h3><div>Adjuvant IAT after successful recanalization may improve functional outcomes in acute ischemic stroke patients without increasing risks. Future studies should focus on identifying ideal candidates and investigating adjunctive approaches to improve microvascular reperfusion.</div></div><div><h3>Systematic review protocol</h3><div>CRD420251001384 <strong>(PROSPERO)</strong></div></div>","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":"1004 ","pages":"Article 178000"},"PeriodicalIF":4.7,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144717777","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":"Loganin and morroniside: Therapeutic effects and molecular mechanisms in diabetes mellitus and its complications—A review","authors":"Wei Jiang ,&nbsp;Kaixi Ding ,&nbsp;Tingting Gong ,&nbsp;Zhipeng Hu ,&nbsp;Rensong Yue ,&nbsp;Maoyi Yang","doi":"10.1016/j.ejphar.2025.177993","DOIUrl":"10.1016/j.ejphar.2025.177993","url":null,"abstract":"<div><div>Diabetes mellitus (DM) and its complications not only seriously affect people's health but also impose a heavy burden on society. It is necessary to strive for further exploration of the pathogenesis of these diseases and the discovery of new drugs. <em>Cornus officinalis</em>, a typical traditional medicinal plant in Asia, is widely recognized for its multiple bioactive effects. Two active ingredients from <em>Cornus officinalis</em>, loganin, and morroniside, have been shown to have antidiabetic effects, such as promoting insulin secretion, improving insulin resistance, and regulating glucose and lipid metabolism. These properties highlight their potential as therapeutic agents in the management of DM. In addition, loganin and morroniside have shown potential therapeutic effects on several diabetic complications, including diabetic nephropathy, diabetic osteoporosis, diabetic testicular injury, diabetic neuropathy, and diabetes-related liver injury. These effects are attributed to their anti-inflammatory, antioxidant, anti-apoptotic, anti-fibrotic, and lipid-modulating properties. This review summarizes the preclinical therapeutic effects and molecular mechanisms of loganin and morroniside related to DM and its complications. Current evidence indicates potential benefits, but the mechanisms require further investigation. Clinical studies are needed to evaluate their efficacy and safety.</div></div>","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":"1003 ","pages":"Article 177993"},"PeriodicalIF":4.7,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144717779","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-depth study of gastrointestinal motility, intestinal barrier function and secretory function in an irritable bowel syndrome post-inflammatory rat model","authors":"Nikita Hanning ,&nbsp;Rosanne Verboven ,&nbsp;Annemieke Smet ,&nbsp;Jean-Pierre Timmermans ,&nbsp;Joris G. De Man ,&nbsp;Benedicte Y. De Winter","doi":"10.1016/j.ejphar.2025.177990","DOIUrl":"10.1016/j.ejphar.2025.177990","url":null,"abstract":"<div><div>The presence of intestinal barrier dysfunction during 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced acute colitis in rats has been well described. However, it has not been studied extensively in the post-inflammatory model of irritable bowel syndrome (IBS) in pharmacological research, despite its frequent use. Therefore, we aimed to explore the intestinal barrier function in post-colitis rats in a comprehensive manner. To do so, colitis was induced in Sprague Dawley rats with a TNBS-enema, after which mucosal healing was followed via repeated colonoscopies. In the post-inflammatory phase, intestinal permeability was assessed <em>in vivo</em> by measuring the recovery of creatinine, 4 kDa FITC-dextran or sugars in serum or urine after orogastric gavage. In addition, Ussing chamber and qPCR experiments were performed. Gastrointestinal motility and renal function were assessed as potential confounders of the <em>in vivo</em> assays. Rats reached the post-inflammatory stage 10–14 days after the administration of TNBS. With the exception of an increased recovery of creatinine and changes in the mRNA expression of some tight junction molecules, no profound signs of intestinal barrier dysfunction were found. Gastric emptying was delayed 30 min after administration of Evans blue but not at later timepoints and no effects on gastric emptying were found using the solid bead assay. Renal function was unaltered in post-colitis animals indicating no confounding effects of renal and motility function. Taken together, the intestinal barrier function remains largely uncompromised in this IBS post-inflammatory rat model, with only a slight but significant effect on pore pathway permeability.</div></div>","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":"1004 ","pages":"Article 177990"},"PeriodicalIF":4.7,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144717778","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":"Reduced circulating levels of CXCL14 are associated with cardiovascular damage in people living with HIV","authors":"Tania Quesada-López ,&nbsp;Alberto Mestres-Arenas ,&nbsp;Pere Domingo ,&nbsp;Paula Prieto ,&nbsp;Isabel Mur ,&nbsp;José Alberto Hidalgo Pérez ,&nbsp;Mariana P. Guimarães ,&nbsp;Joan Villarroya ,&nbsp;María del Mar Gutiérrez ,&nbsp;María Gracia Mateo ,&nbsp;Joan Carles Domingo ,&nbsp;Anna Planavila ,&nbsp;Francesc Villarroya ,&nbsp;Marta Giralt ,&nbsp;Rubén Cereijo","doi":"10.1016/j.ejphar.2025.177996","DOIUrl":"10.1016/j.ejphar.2025.177996","url":null,"abstract":"<div><div>Combined antiretroviral therapy (cART) has improved quality of life of people living with HIV (PLWH). However, alterations in adiposity with concomitant cardiovascular disease (CVD) and circulating systemic disturbances reminiscent of the metabolic syndrome still occur. We recently identified chemokine C-X-C motif ligand 14 (CXCL14) as a brown adipokine involved in M2 macrophage migration to adipose tissues to promote energy expenditure and insulin sensitivity, also exerting cardioprotective actions. Here, we aimed to study CXCL14 regulation and potential association with CVD in PLWH. Serum levels of CXCL14 and adipocytokines of interest were quantified in cohort of 50 cART-treated PLWH and 38 age- and sex-matched controls (50.6 ± 10.1 years, 74.1 % males). Adipose biopsies were extracted for <em>CXCL1</em>4 mRNA expression assessment using RT-qPCR. Cardiac computed tomography angiography with contrast-enhanced scan was used to determine atherosclerotic coronary burden, and multivariant models were used to integrate data. CXCL14 circulating levels and mRNA expression in subcutaneous fat were reduced in cART-treated PLWH, especially women. While no association with insulin resistance was observed, circulating CXCL14 negatively correlated with visceral adiposity and tumor necrosis factor alpha (TNFα), fibroblast growth factor 23 (FGF23) and phospholipase A2 Group VII (PLA2G7) levels, and with presence of noncalcified atheromatous plaque in PLWH. This reduction in CXCL14 levels and negative association with inflammation and visceral fat in cART-treated PLWH were reminiscent of its regulation in diabesity. Despite further research is needed, association of circulating CXCL14 with noncalcified atheromatous plaque can result in applications as a novel subclinical biomarker for CVD in PLWH.</div></div>","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":"1003 ","pages":"Article 177996"},"PeriodicalIF":4.2,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144713040","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":"Salidroside ameliorates monocrotaline-induced pulmonary arterial hypertension in rats by modulating BKCa channels","authors":"Guo-Qing Lu ,&nbsp;Hong-Yan Sun ,&nbsp;Mei-Yang Xu ,&nbsp;Zheng-Yu Sun ,&nbsp;Ying Tang ,&nbsp;Qing Chen ,&nbsp;Wen-Di Jiang ,&nbsp;Zi-Yi Chen ,&nbsp;Lei Wang ,&nbsp;Le-Qiang Liu ,&nbsp;Hong-Ju Wang ,&nbsp;Qin Gao ,&nbsp;Bi Tang ,&nbsp;Pin-Fang Kang","doi":"10.1016/j.ejphar.2025.177950","DOIUrl":"10.1016/j.ejphar.2025.177950","url":null,"abstract":"<div><div>Salidroside (Sal) is a natural active ingredient extracted from Crassulaceae plants, which has pharmacological effects such as anti-tumor, anti-oxidation, and cardiovascular protection. Potassium channel function in pulmonary artery smooth muscle cells (PASMCs) is crucial in the development of pulmonary arterial hypertension (PAH). This study explored the effects of Sal on large-conductance calcium-activated potassium channels (BKCa) in these cells, focusing on the mechanisms underlying its protective effect in PAH. A rat model of PAH was established using monocrotaline (MCT) alongside an in vitro model of primary PASMCs stimulated by platelet-derived growth factor-BB. This study thoroughly assesses Salidroside's impact on PAH across tissue function, molecular mechanisms, and electrophysiological characteristics. Our results show that Sal treatment reduced right ventricular pressure in MCT-induced PAH rats, ameliorated pulmonary vascular remodeling and right ventricular reconstruction, and enhanced pulmonary vasoconstriction and relaxation activity. It increased the expression of BKCa channel proteins on the membrane of PASMCs, inhibited the proliferation of PASMCs, promoted their apoptosis, and improved the electrophysiological remodeling of PASMCs and pulmonary vascular remodeling caused by PAH. Activation and excessive expression of PKC α markedly suppressed BKCa channel function. Sal was able to activate BKCa channels by inhibiting PKC α, leading to enhanced K⁺ efflux, cellular hyperpolarization, and vasodilation. In conclusion,by reinstating BKCa channel activity in PASMCs, Sal rectified the dysregulation between cell proliferation and apoptosis within the pulmonary vasculature. This mechanism, potentially mediated indirectly by Sal's modulation of PKC α, offers a novel therapeutic approach for PAH.</div></div>","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":"1004 ","pages":"Article 177950"},"PeriodicalIF":4.7,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144717782","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":"Repositioning of a nutraceutical, scoparone, in the management of MK-801-induced schizophrenia-like behavior in Mice: An insight into SIRT1/PGC-1α/TFAM pathway","authors":"Mostafa A. Rabie ,&nbsp;Wagih H. Marcus ,&nbsp;Mohamed A. Sadek ,&nbsp;Hassan A. Ruby ,&nbsp;Khloud A.F. Emam ,&nbsp;Barbara Budzynska ,&nbsp;Krystyna Skalicka-Wożniak ,&nbsp;Rabab H. Sayed ,&nbsp;Lamiaa A. Ahmed ,&nbsp;Nesrine S. El Sayed","doi":"10.1016/j.ejphar.2025.177981","DOIUrl":"10.1016/j.ejphar.2025.177981","url":null,"abstract":"<div><div>Schizophrenia is a prevalent neurodevelopmental psychiatric disorder that remains inadequately managed by current treatments, highlighting the urgent need for new pharmacotherapeutic approaches. Nutraceuticals have gained attention due to their favorable safety and multifaceted pharmacological benefits. Among these, scoparone exhibits a well-documented neuropsychopharmacological profile; however, its potential therapeutic effects on schizophrenia remain unclear and warrant further investigation. Consequently, this study aimed to evaluate the influence of scoparone treatment on MK-801-induced schizophrenia-like behaviors in C57BL/6 mice. C57BL/6 mice were injected with MK-801 (0.6 mg/kg/day, i.p.) for 7 consecutive days to induce schizophrenia. Mice were treated with scoparone (25 mg/kg/day, i.p.) 2 h after the MK-801 administration. Interestingly, scoparone attenuated MK-801-induced positive, negative, and cognitive symptoms of schizophrenia, as demonstrated in behavioral tests. Furthermore, it hindered MK-801-induced histopathological changes in the hippocampus. Importantly, the biochemical analysis shed light on the ability of scoparone to activate the neuroprotective silent mating type information regulation 2 homolog 1/peroxisome proliferator-activated receptor-γ coactivator-1-α/mitochondrial transcription factor A (SIRT1/PGC-1α/TFAM) signaling pathway, thereby regulating mitochondrial homeostasis. Concisely, PGC-1α activation hinders dynamin-related protein 1 (Drp1) levels, restricting mitochondrial fission. Conversely, it augments the fusion of adjacent mitochondria by boosting Mitofusin 2 (MFN2) and protein optic atrophy 1 (OPA1) levels. Moreover, it enhanced mitophagy for selective removal of damaged mitochondria. In conclusion, this study underscores scoparone's beneficial effect in MK-801-induced schizophrenia-like behaviors <em>via</em> SIRT1 activation, which manipulates multiple axes involved in the pathophysiology of schizophrenia.</div></div>","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":"1004 ","pages":"Article 177981"},"PeriodicalIF":4.7,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144717781","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":"Luteolin targets peroxiredoxin 2 to augment T-cell-mediated cytotoxicity and suppress lung adenocarcinoma progression","authors":"Xuan Li ,&nbsp;Ying Bai ,&nbsp;Jiawei Zhou ,&nbsp;Anqi Cheng ,&nbsp;Jianqiang Guo ,&nbsp;Maoqian Chen ,&nbsp;Dong Hu ,&nbsp;Jing Wu","doi":"10.1016/j.ejphar.2025.177984","DOIUrl":"10.1016/j.ejphar.2025.177984","url":null,"abstract":"<div><div>Lung adenocarcinoma (LUAD), as a prevalent and life-threatening malignancy, poses a significant global health burden, particularly impacting patients and their families profoundly. Peroxiredoxin-2 (PRDX2) exhibits high expression levels in LUAD tissues. However, the identification of efficient and low-toxicity small-molecule inhibitors targeting PRDX2 from traditional Chinese medicine remains a challenging task. This study aims to identify potential inhibitors of PRDX2 in lung adenocarcinoma and elucidate their mechanism of action. Molecular docking and thermal shift assays were employed to evaluate the interaction between luteolin and PRDX2 protein. The effects of luteolin on lung cancer cell behavior were assessed through in vitro cellular experiments, and its efficacy on tumor growth was validated in a mouse model. Additionally, flow cytometry and Western blot analysis were utilized to investigate the mechanism of luteolin's action. Molecular docking and thermal shift experiments confirmed the binding affinity of luteolin to PRDX2. In vitro experiments demonstrated that luteolin significantly inhibits the proliferation and migration of LUAD cells. In vivo experiments showed that luteolin effectively suppresses tumor growth in an immunocompetent lung cancer mouse model. Western blot results untangled that luteolin promotes apoptosis of lung cancer cells by enhancing T-cell-mediated killing pathways via PRDX2. In summary, luteolin binds to PRDX2, inhibiting the JAK2/STAT3 pathway, suppressing PD-L1 expression, promoting the release of perforin and granzyme B from CD8⁺ T cells, and inhibiting immune evasion in LUAD, thereby inhibiting the progression of lung adenocarcinoma.</div></div>","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":"1004 ","pages":"Article 177984"},"PeriodicalIF":4.7,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144717780","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":"Taurine alleviates oxidative stress, inflammation, and mitochondrial apoptosis in lipopolysaccharide-induced bovine endometrial epithelial cells by activating nrf2/HO-1 and inhibiting TLR4-mapk/NF-κb and Caspase-3 pathways","authors":"Jianxu Xiao ,&nbsp;Ming Yang ,&nbsp;Ke Li ,&nbsp;Zhongkun Guo ,&nbsp;Likun Chen ,&nbsp;Li Jia ,&nbsp;Wei Yang ,&nbsp;Ning Zhang ,&nbsp;Yuzhong Ma","doi":"10.1016/j.ejphar.2025.177986","DOIUrl":"10.1016/j.ejphar.2025.177986","url":null,"abstract":"<div><div>Bovine endometritis negatively impacts reproductive performance and causes significant economic losses in the dairy industry. Taurine is known for its antioxidant and anti-inflammatory properties; however, its protective roles in bovine endometritis remain unclear. This study aimed to investigate the protective effects of taurine against injury in lipopolysaccharide (LPS)-induced bovine endometrial epithelial cells. The results confirmed that taurine treatment protected LPS-induced cells in a time- and dose-dependent manner. First, oxidative stress was alleviated by increasing the activities of superoxide dismutase and glutathione, as well as upregulating protein expression in the nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) pathway, while decreasing levels of malondialdehyde and reactive oxygen species. Second, inflammation was reduced by suppressing mRNA expression of Toll-like receptor 4 (TLR4) and proinflammatory cytokines, and by decreasing phosphorylation of extracellular signal-regulated kinase, p38 mitogen-activated protein kinase, c-Jun N-terminal kinase, inhibitor of kappa B alpha, and nuclear factor kappa B p65 subunit in the nuclear factor kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) pathways. Third, mitochondrial apoptosis was mitigated by restoring mitochondrial membrane potential and modulating apoptosis-related protein levels. Overall, taurine acts as a natural protective agent against LPS-induced damage in bovine endometrial epithelial cells through its antioxidant, anti-inflammatory, and anti-apoptotic effects via modulation of the Nrf2/HO-1, TLR4-MAPK/NF-κB, and cysteine-aspartic acid protease-3 pathways. These findings highlight taurine's potential as a therapeutic agent for bovine endometritis.</div></div>","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":"1003 ","pages":"Article 177986"},"PeriodicalIF":4.2,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144706865","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":"Systemic administration of Neochamaejasmin B inhibits mast cell activation to reduce inflammation in a rosacea mouse model by targeting MRGPRX2","authors":"Yi Zheng ,&nbsp;Mengyao Yi ,&nbsp;Tao Jia ,&nbsp;Yifan Xia ,&nbsp;Yuxin Zhang ,&nbsp;Weihui Zeng ,&nbsp;Delu Che","doi":"10.1016/j.ejphar.2025.177988","DOIUrl":"10.1016/j.ejphar.2025.177988","url":null,"abstract":"<div><div>Rosacea is a chronic inflammatory disease characterised by facial erythema, telangiectasia, papules, pustules, and ocular manifestations. Mas-related G protein-coupled receptor X2 (MRGPRX2), suggested as a key receptor in the pathogenesis and inflammation of rosacea, is a potential therapeutic target to treat rosacea. Antibiotics are used to treat rosacea; however, drugs for targeted treatment are lacking. Few studies have investigated drugs that inhibit MRGPRX2 expression in rosacea. Neochamaejasmin B (NCB), the most abundant component in the dried roots of the toxic perennial herb <em>Stellera chamaejasme</em> L., exhibits various pharmacological activities, including anti-inflammatory effects. However, the pharmacological mechanism of NCB remains unclear. In this study, we investigated the effect of NCB on the inhibition of MRGPRX2 activation in an LL-37-induced rosacea mouse model. Hematoxylin and eosin staining, immunohistochemistry, and immunofluorescence staining were used to evaluate the effects of NCB on pathogenesis. Inflammatory mediators were measured using RNA sequencing and enzyme-linked immunosorbent assay. The MRGPRX2-mediated mast cell (MC) degranulation model, molecular docking, molecular dynamics simulations, and surface plasmon resonance were used to evaluate the inhibitory effect of NCB on MRGPRX2. Finally, the downstream signalling pathway of MRGPRX2 was analyzed by western blotting. NCB reduced the pathogenesis and inflammation of rosacea <em>in vivo</em> by inhibiting MC activation and MRGPRX2-mediated MC activation <em>in vitro</em>. NCB showed a strong binding affinity for MRGPRX2 and inhibited NF-κB pathway activation. Our study showed that NCB reduced the pathogenesis and inflammation of rosacea by inhibiting MRGPRX2 activation.</div></div>","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":"1003 ","pages":"Article 177988"},"PeriodicalIF":4.2,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144685479","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}