European journal of pharmacology最新文献

{"title":"Dimethyl fumarate is repurposed to ameliorate aortic aneurysm and dissection in mice","authors":"Xuan Wang ,&nbsp;Jin Kuang ,&nbsp;Xiao-Tian Li ,&nbsp;Xi Hu ,&nbsp;Yu-Hang Liu ,&nbsp;Chang-Ping Hu ,&nbsp;Mi Wang ,&nbsp;Qing Wang ,&nbsp;Zheng Zhang","doi":"10.1016/j.ejphar.2024.177215","DOIUrl":"10.1016/j.ejphar.2024.177215","url":null,"abstract":"<div><div>Aortic aneurysm and dissection pose fatal threats but no effective drug therapies are available. Previous work has been directed to reduce risk factors or target key pathological events, but none of the translational efforts succeeds. Here, we attempt to repurpose dimethyl fumarate (DMF), an FDA-approved immunomodulatory drug for multiple sclerosis, for the treatment of aortic aneurysm and dissection. In three preclinical mouse models of abdominal aortic aneurysm (porcine pancreatic elastase perfusion or CaCl₂ incubation) and thoracic aortic aneurysm and dissection (β-Aminopropionitrile feeding), DMF invariably protected mice from aneurysm growth, aortic dissection, rupture and death. Histological H&amp;E and EVG staining demonstrated aortic architecture-preserving effects of DMF. Through transcriptome profiling and the connectivity map (CMap), we showed that DMF restored SRC-FAK signaling in aortic smooth muscle cells and increased collagen I turnover in the tunica media. Our work suggests the potential of DMF being repurposed for aortic aneurysm and dissection, and highlights the importance of SRC-FAK signaling in aortic homeostasis.</div></div>","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":"988 ","pages":"Article 177215"},"PeriodicalIF":4.2,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142871712","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":"Effects of canagliflozin preconditioning on post-resuscitation myocardial function in a diabetic rat model of cardiac arrest and cardiopulmonary resuscitation","authors":"Minjie Wang ,&nbsp;Tianfeng Hua ,&nbsp;Yijun Zhang ,&nbsp;Qihui Huang ,&nbsp;Wei Shi ,&nbsp;Yuqian Chu ,&nbsp;Yan Hu ,&nbsp;Sinong Pan ,&nbsp;Bingrui Ling ,&nbsp;Wanchun Tang ,&nbsp;Min Yang","doi":"10.1016/j.ejphar.2024.177212","DOIUrl":"10.1016/j.ejphar.2024.177212","url":null,"abstract":"<div><h3>Background</h3><div>Canagliflozin can reduce the risk of cardiovascular disease in patients except for its targeted antidiabetic effects. However, it remains unknown whether canagliflozin alleviates the post-resuscitation myocardial dysfunction (PRMD) in type 2 diabetes mellitus.</div></div><div><h3>Objective</h3><div>To explore the effects and potential mechanisms of canagliflozin on myocardial function after cardiac arrest (CA) and cardiopulmonary resuscitation (CPR) in a type 2 diabetic rat model.</div></div><div><h3>Methods</h3><div>Twenty-four type 2 diabetic rats were randomized into four groups: (1) sham + canagliflozin, (2) sham + placebo, (3) CPR + placebo, and (4) CPR + canagliflozin. Except for the sham + canagliflozin and placebo groups, both the CPR + placebo and canagliflozin groups underwent 8 min of CPR after the induction of ventricular fibrillation for 6 min. Myocardial function and hemodynamics were assessed at baseline and within 6 h after autonomous circulation (ROSC) return. Left ventricular tissues were sampled to determine the expressions of relevant proteins in the NLRP3 inflammasome pathway.</div></div><div><h3>Results</h3><div>The results demonstrated that the mean arterial pressure (MAP) was significantly improved in the CPR + canagliflozin group after ROSC compared with the CPR + placebo group (p &lt; 0.05). Meanwhile, both ejection fraction (EF) and fraction shortening (FS) were dramatically increased in the CPR + canagliflozin group when compared with the CPR + placebo group at 2h, 4h, and 6h after ROSC (p &lt; 0.05). In addition, the levels of NT-proBNP, cTn-I, and NLRP3 inflammatory inflammasome-associated proteins were significantly decreased in the CPR + canagliflozin group compared with the CPR + placebo group.</div></div><div><h3>Conclusions</h3><div>In type 2 diabetic rats, pretreatment of canagliflozin alleviates PRMD. The potential mechanisms may include inhibition of the NLRP3/caspase-1 signaling pathway.</div></div>","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":"988 ","pages":"Article 177212"},"PeriodicalIF":4.2,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142871714","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 efficacy of targeted therapy and/or immunotherapy with or without chemotherapy in patients with colorectal cancer: A network meta-analysis","authors":"Haoyan Guo ,&nbsp;Longjie Miao ,&nbsp;Chengdong Yu","doi":"10.1016/j.ejphar.2024.177219","DOIUrl":"10.1016/j.ejphar.2024.177219","url":null,"abstract":"<div><h3>Background</h3><div>The use of targeted drugs and immunotherapy has significantly impacted the treatment of Colorectal Cancer. However, horizontal comparison among various regimens is extremely rare. Therefore, we evaluated the survival efficacy of multiple treatment regimens of targeted therapy and/or immunotherapy with or without chemotherapy in patients with Colorectal Cancer.</div></div><div><h3>Methods</h3><div>A systematic search was conducted in PubMed, EMBASE, and Cochrane databases, covering the period from the establishment of the databases to October 29, 2024. To obtain articles that met the inclusion and exclusion criteria and contained the required data for conducting a network meta-analysis (NMA). The NMA evaluated overall survival (OS) and progression-free survival (PFS).</div></div><div><h3>Results</h3><div>A total of 90 studies were identified, comprising a sample size of 33,167 subjects. In terms of PFS, compared with simple chemotherapy strategies, most of the other single or combined strategies are significantly effective, among which targeted therapy strategies have more advantages. Encorafenib + Binimetinib + Cetuximab (ENC-BIN-CET) shows significant benefits in all comparisons except when compared with Chemotherapy + Cetuximab + Dalotuzumab (Chemo-CET-DAL), Encorafenib + Cetuximab (ENC-CET), and Panitumumab + Sotorasib (PAN-SOT). The ENC-CET and PAN-SOT targeted strategies also show significant benefits. Pembrolizumab (PEM) monotherapy has advantages over all others except when it is not superior to some targeted strategies. Chemotherapy + Bevacizumab + Atezolizumab is only inferior to some strategies. In terms of OS, the combinations of Chemotherapy + Bevacizumab, ENC-CET, Chemotherapy + Panitumumab, and ENC-BIN-CET are superior to simple chemotherapy regimens. ENC-BIN-CET shows OS benefits in all comparisons except some. ENC-CET significantly improves OS in most cases, and PEM also significantly improves OS in some regimens. In the probability ranking of OS and PFS, ENC-BIN-CET has the best effect, followed by ENC-CET.</div></div><div><h3>Conclusions</h3><div>In conclusion, pembrolizumab is still effective in prolonging survival. Dual- and triple-drug targeted strategies are the best in terms of OS and PFS, and the combination of targeted immunotherapy and chemotherapy also works. However, not all combinations are beneficial. As targeted drugs play an active role, specific drugs for colorectal cancer regimens should be carefully selected.</div></div>","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":"988 ","pages":"Article 177219"},"PeriodicalIF":4.2,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142880672","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":"Phosphatidic acid as a cofactor of mTORC1 in platinum-based chemoresistance: Mechanisms and therapeutic potential","authors":"Hadi Alizadeh,&nbsp;Sana Kerachian,&nbsp;Keyvan Jabbari,&nbsp;Bahram Mohammad Soltani","doi":"10.1016/j.ejphar.2024.177220","DOIUrl":"10.1016/j.ejphar.2024.177220","url":null,"abstract":"<div><div>Platinum-based chemotherapeutics, such as cisplatin and carboplatin, are widely used to treat various malignancies. However, the development of chemoresistance remains a significant challenge, limiting their efficacy. This review explores the multifaceted mechanisms of platinum-based chemoresistance, with a particular focus on the mammalian target of rapamycin complex 1 (mTORC1) signaling pathway, which plays a critical role in promoting tumor survival and resistance to platinum compounds. Additionally, we examined the role of phosphatidic acid (PA) and its synthesizing enzymes, phospholipase D (PLD) and lysophosphatidic acid acyltransferase (LPAAT), in the regulation of mTORC1 activity. Given the involvement of mTORC1 in chemoresistance, we evaluated the potential of mTOR inhibitors as a therapeutic strategy to overcome platinum resistance. Finally, we discuss combination therapies targeting the mTOR pathway alongside conventional chemotherapy to improve treatment outcomes. This review highlights the potential of targeting mTORC1 and related pathways to improve therapeutic strategies for chemoresistant cancers.</div></div>","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":"988 ","pages":"Article 177220"},"PeriodicalIF":4.2,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142880658","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":"Orofacial pain models induce impairment in spatial learning and working memory in rodents: A systematic review and meta-analysis","authors":"Fernanda Tibolla Viero,&nbsp;Ricardo Iuri Felix Morais,&nbsp;Patrícia Rodrigues,&nbsp;Sabrina Qader Kudsi,&nbsp;Leonardo Gomes Pereira,&nbsp;Gabriela Trevisan","doi":"10.1016/j.ejphar.2024.177225","DOIUrl":"10.1016/j.ejphar.2024.177225","url":null,"abstract":"<div><div>Orofacial pain is one of the most common causes of chronic pain leading to physical and cognitive disability. Several clinical and pre-clinical studies suggest that chronic pain results in cognitive impairment. However, there is a lack of meta-analyses examining the effects of orofacial pain models on behavioral learning and memory in rodents. Thus, this study aimed to evaluate whether orofacial pain models can impair learning and memory in rodents. The protocol was registered in PROSPERO (CRD42023355502). We used CAMARADES and SYRCLE to estimate the quality and the publication bias by using Egger's and Begg's test. Here, 21 studies were included in this systematic review and meta-analysis. We included 12 studies with trigeminal neuralgia models, 4 with migraine-like pain models, 4 with tooth nociception, and 1 with acute orofacial pain model. Spontaneous nociception and facial mechanical allodynia were observed in orofacial pain models. Regarding spatial learning we detected that latency to find the platform in the Morris water maze (MWM) was increased in orofacial pain models (related to facial mechanical allodynia or spontaneous nociception). Although the mean quality of the articles was high, we identify publication bias in the Begg's test for the time in the quadrant in the MWM. Our findings revealed that spontaneous nociception and facial mechanical allodynia in orofacial pain models contribute to the working memory and spatial learning dysfunction. Therefore, further studies are still needed to evaluate the influence of sex, age, social isolation, and environmental enrichment in orofacial pain-related learning and memory.</div></div>","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":"988 ","pages":"Article 177225"},"PeriodicalIF":4.2,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142909493","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 phosphodiesterase-4 inhibitor Zl-n-91 suppresses glioblastoma growth via EGR1/PTEN/AKT pathway","authors":"Yuyu Li ,&nbsp;Xin He ,&nbsp;Shiri Li ,&nbsp;Shenjie Chen ,&nbsp;Zhenggang Zhao ,&nbsp;Yunping Mu ,&nbsp;Allan Z. Zhao ,&nbsp;Sujin Zhou ,&nbsp;Fanghong Li","doi":"10.1016/j.ejphar.2024.177230","DOIUrl":"10.1016/j.ejphar.2024.177230","url":null,"abstract":"<div><div>Glioblastoma multiforme (GBM) is a highly heterogeneous and aggressive brain tumor, which presents significant challenges for treatment in clinical settings. Phosphodiesterase 4 (PDE4) inhibitors can prevent the degradation of cAMP and have been used as a potential targeted therapeutic approach for different cancer types. However, their clinical use is restricted by side effects such as nausea and vomiting. Herein, we investigated the efficacy and therapeutic mechanisms of a specific PDE4 inhibitor, Zl-n-91, on GBM cells. The results demonstrated that Zl-n-91 exhibited greater effectiveness than the well-known PDE4 inhibitor Rolipram in treating GBM. It can notably suppress the proliferation of GBM cells by inducing G0/G1 phase arrest and apoptosis. Additionally, Zl-n-91 significantly inhibited the growth of subcutaneous glioma xenografts. Mechanistically, Zl-n-91 treatment increased the expression and nuclear transcription of Early growth response (EGR1), while knockdown of EGR1 could decrease PTEN levels and increase p-AKT levels, restoring the inhibition of cell proliferation induced by Zl-n-91. Collectively, we revealed for the first time that PDE4 inhibitor Zl-n-91 could inhibit the growth of GBM cells through the EGR1/PTEN/AKT signaling pathway. Zl-n-91, a specific PDE4 inhibitor, may be a promising therapeutic candidate for GBM.</div></div>","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":"988 ","pages":"Article 177230"},"PeriodicalIF":4.2,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142893241","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":"Protective effect of Astragaloside II against lung injury in COPD based on mTORC1/GSK-3β signaling pathway","authors":"Fengxi Chen ,&nbsp;Yeqing Zhang ,&nbsp;Xuejian Wang ,&nbsp;Mei Jing ,&nbsp;Ling Zhang ,&nbsp;Ke Pei ,&nbsp;Tong Zhao ,&nbsp;Kelei Su","doi":"10.1016/j.ejphar.2024.177214","DOIUrl":"10.1016/j.ejphar.2024.177214","url":null,"abstract":"<div><h3>Background</h3><div>Astragaloside II (AST II) is one of the principal bioactive components of <em>Astragalus mongholicus</em> Bunge, exhibiting multiple pharmacological properties. However, the therapeutic efficacy of AST II in Chronic Obstructive Pulmonary Disease (COPD) remains to be fully elucidated. The study explored the effects and mechanisms of AST II in a COPD model induced by exposure to cigarette smoke (CS) and lipopolysaccharide (LPS) in mice.</div></div><div><h3>Methods</h3><div>An animal model of COPD was established by intratracheal instillation of LPS and cigarette smoking in mice. Serum samples were collected to determine inflammatory cell infiltration and cytokine levels. Lung tissues were collected for histological, immunofluorescence and Western blot analysis. The RAW264.7 macrophage cell line was employed to investigate the molecular mechanism of AST II in vitro.</div></div><div><h3>Results</h3><div>Lung dysfunction, histopathological damage, inflammatory infiltration, and pro-inflammatory factors secretion in COPD mice induced by CS and LPS were mitigated by AST II. AST II exerted an anti-inflammatory effect by enhancing the activation of the mammalian target of rapamycin complex 1 (mTORC1)/glycogen synthase kinase-3β (GSK-3β) signaling pathway, which promoted the binding of CREB-binding protein (CBP) to CREB, thereby antagonizing the binding to nuclear factor-κB (NF-κB) and inhibiting its transcriptional activity. However, AST II did not demonstrate a protective effect against LPS-induced inflammatory damage to RAW264.7 cells when mTORC1 was inhibited by rapamycin.</div></div><div><h3>Conclusion</h3><div>AST II exhibits potential therapeutic benefits as an alternative medication for COPD and other respiratory inflammatory conditions since it may reduce lung injury and inflammatory response in mice exposed to CS and LPS.</div></div>","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":"988 ","pages":"Article 177214"},"PeriodicalIF":4.2,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142871666","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":"NRF-mediated autophagy and UPR: Exploring new avenues to overcome cancer chemo-resistance","authors":"Sanaz Dastghaib ,&nbsp;Sayed Mohammad Shafiee ,&nbsp;Fatemeh Ramezani ,&nbsp;Niloufar Ashtari ,&nbsp;Farhad Tabasi ,&nbsp;Javad Saffari-Chaleshtori ,&nbsp;Morvarid Siri ,&nbsp;Omid Vakili ,&nbsp;Somayeh Igder ,&nbsp;Mozhdeh Zamani ,&nbsp;Maryam Niknam ,&nbsp;Mahshid Moballegh Nasery ,&nbsp;Fariba Kokabi ,&nbsp;Emilia Wiechec ,&nbsp;Zohreh Mostafavi-Pour ,&nbsp;Pooneh Mokarram ,&nbsp;Saeid Ghavami","doi":"10.1016/j.ejphar.2024.177210","DOIUrl":"10.1016/j.ejphar.2024.177210","url":null,"abstract":"<div><div>The development of chemo-resistance remains a significant hurdle in effective cancer therapy. NRF1 and NRF2, key regulators of redox homeostasis, play crucial roles in the cellular response to oxidative stress, with implications for both tumor growth and resistance to chemotherapy. This study delves into the dualistic role of NRF2, exploring its protective functions in normal cells and its paradoxical support of tumor survival and drug resistance in cancerous cells. We investigate the interplay between the PERK/NRF signaling pathway, ER stress, autophagy, and the unfolded protein response, offering a mechanistic perspective on how these processes contribute to chemoresistance. Our findings suggest that targeting NRF signaling pathways may offer new avenues for overcoming resistance to chemotherapeutic agents, highlighting the importance of a nuanced approach to redox regulation in cancer treatment. This research provides a molecular basis for the development of NRF-targeted therapies, potentially enhancing the efficacy of existing cancer treatments and offering hope for more effective management of resistant tumors.</div></div>","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":"988 ","pages":"Article 177210"},"PeriodicalIF":4.2,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142871715","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Isoquinolinequinone N-oxides with diverging mechanisms of action induce collateral sensitivity against multidrug resistant cancer cells","authors":"Mélanie A.G. Barbosa ,&nbsp;Ryan D. Kruschel ,&nbsp;Maria João Almeida ,&nbsp;Rúben F. Pereira ,&nbsp;Cristina P.R. Xavier ,&nbsp;Florence O. McCarthy ,&nbsp;M. Helena Vasconcelos","doi":"10.1016/j.ejphar.2024.177234","DOIUrl":"10.1016/j.ejphar.2024.177234","url":null,"abstract":"<div><div>Multidrug resistance (MDR) is a major challenge in cancer research. Collateral sensitizers, compounds that exploit the enhanced defense mechanisms of MDR cells as weaknesses, are a proposed strategy to overcome MDR. Our previous work reported the synthesis of two novel Isoquinolinequinone (IQQ) <em>N</em>-oxides that induce collateral sensitivity in MDR ABCB1-overexpressing non-small cell lung cancer (NSCLC) and colorectal cancer cells. Herein, we aimed to investigate underlying mechanisms of antitumor and collateral sensitivity activity of these compounds. We evaluated their effect on cancer cell viability, proliferation, cell cycle profile, and studied their cytotoxicity in non-tumorigenic cells. Their antitumor effect was further studied using NSCLC and colorectal cancer MDR spheroids. To understand underlying collateral sensitivity mechanisms, we assessed the effect on rhodamine-123 accumulation, ROS production, GSH/GSSG balance and expression of key proteins associated with metabolism and redox balance. Both compounds reduced the viability of MDR cells, as 2D cultures or as spheroids, without decreasing the growth of a human nontumorigenic cell line, and increased rhodamine-123 accumulation in MDR NCI-H460/R cells. Moreover, RK2 increased ROS, disrupted GSH balance, and altered expression of proteins associated with oxidative stress protection, particularly in NCI-H460/R cells. The collateral sensitivity effect of RK3 could not be attributed to redox balance disruption, but increased IDH1 expression following treatment suggests a potential metabolic shift in MDR cells. These findings highlight RK2 and RK3 as promising candidates for next stages of drug development. Their distinct mechanisms of action could lead to therapeutic solutions for MDR-related cancers, specifically linked to ABCB1 overexpression.</div></div>","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":"988 ","pages":"Article 177234"},"PeriodicalIF":4.2,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142893213","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":"Repeated intermittent administration of 3,4-methylenedioxymethamphetamine mitigates demyelination in the brain from cuprizone-treated mice.","authors":"Mingming Zhao, Akifumi Eguchi, Rumi Murayama, Dan Xu, Tingting Zhu, Biao Xu, Guiling Liu, Chisato Mori, Jianjun Yang, Kenji Hashimoto","doi":"10.1016/j.ejphar.2025.177345","DOIUrl":"https://doi.org/10.1016/j.ejphar.2025.177345","url":null,"abstract":"<p><p>3,4-Methylenedioxymethamphetamine (MDMA), commonly known as a recreational drug, may also offer therapeutic benefits for mental health. Population-based studies suggest that MDMA users have a lower risk of demyelinating diseases, such as depression. Given the role of the gut microbiota in mediating MDMA's effects, we hypothesized that MDMA might confer mental health benefits via the gut-brain axis. Cuprizone (CPZ) induces demyelination by chelating copper, which leads to oligodendrocyte death and subsequent myelin loss. This study investigated the impact of MDMA on brain demyelination in CPZ-treated mice, focusing on the gut-brain axis. Repeated intermittent MDMA administration (10 mg/kg, three times weekly for 6 weeks) significantly reduced demyelination in the corpus callosum (CC) of CPZ-treated mice. Gut microbiota and non-targeted metabolomics analyses revealed notable differences in specific gut bacteria and plasma (β-D-allose and L-sorbose) or fecal metabolite (carnitine) levels between MDMA-treated and vehicle-treated CPZ-exposed mice. Negative correlations were found between the levels of metabolites (β-D-allose, L-sorbose, and carnitine) and the relative abundance of Romboutsia and Romboutsia timonensis. These findings suggest that intermittent MDMA administration may alleviate demyelination in the CC of CPZ-treated mice via the gut-brain axis. Further research is needed to elucidate the roles of gut microbiota and metabolites in MDMA's effects on brain demyelination and to investigate other demyelination models.</p>","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":" ","pages":"177345"},"PeriodicalIF":4.2,"publicationDate":"2025-02-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143188842","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}