European journal of pharmacology最新文献_第10页

PI3K/AKT pathway: A potential therapeutic target in cerebral ischemia-reperfusion injury

IF 4.2 3区医学

European journal of pharmacology Pub Date : 2025-03-19 DOI: 10.1016/j.ejphar.2025.177505

Yiming Han , Yu Sun , Shiyu Peng , Tingting Tang , Beibei Zhang , Ruonan Yu , Xiaoyan Sun , Shanshan Guo , Lijuan Ma , Peng Li , Pengfei Yang

{"title":"PI3K/AKT pathway: A potential therapeutic target in cerebral ischemia-reperfusion injury","authors":"Yiming Han , Yu Sun , Shiyu Peng , Tingting Tang , Beibei Zhang , Ruonan Yu , Xiaoyan Sun , Shanshan Guo , Lijuan Ma , Peng Li , Pengfei Yang","doi":"10.1016/j.ejphar.2025.177505","DOIUrl":"10.1016/j.ejphar.2025.177505","url":null,"abstract":"<div><div>Cerebral ischemia is a prevalent cerebrovascular disorder, with the restoration of blocked blood vessels serving as the current standard clinical treatment. However, reperfusion can exacerbate neuronal damage and neurological dysfunction, resulting in cerebral ischemia-reperfusion (I/R) injury. Presently, clinical treatment strategies for cerebral I/R injury are limited, creating an urgent need to identify new effective therapeutic targets. The PI3K/AKT signaling pathway, a pro-survival pathway associated with cerebral I/R injury, has garnered significant attention. We conducted a comprehensive review of the literature on the PI3K/AKT pathway in the context of cerebral I/R. Our findings indicate that activation of the PI3K/AKT signaling pathway following cerebral I/R can alleviate oxidative stress, reduce endoplasmic reticulum stress (ERS), inhibit inflammatory responses, decrease neuronal apoptosis, autophagy, and pyroptosis, mitigate blood-brain barrier (BBB) damage, and promote neurological function recovery. Consequently, this pathway ultimately reduces neuronal death, alleviates brain tissue damage, decreases the volume of cerebral infarction, and improves behavioral impairments. These results suggest that the PI3K/AKT signaling pathway is a promising therapeutic target for further research and drug development, holding significant potential for the treatment of cerebral I/R injury.</div></div>","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":"998 ","pages":"Article 177505"},"PeriodicalIF":4.2,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143673731","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}

引用次数: 0

Chlorogenic acid alleviates DNCB-induced atopic dermatitis by inhibiting the Akt1/NF-κB signaling pathway

IF 4.2 3区医学

European journal of pharmacology Pub Date : 2025-03-19 DOI: 10.1016/j.ejphar.2025.177534

Wenkai Nie , Xuan Zhao , Yan Zhang , Cheng Zeng , Huiwen Yang , Bing Liu

{"title":"Chlorogenic acid alleviates DNCB-induced atopic dermatitis by inhibiting the Akt1/NF-κB signaling pathway","authors":"Wenkai Nie , Xuan Zhao , Yan Zhang , Cheng Zeng , Huiwen Yang , Bing Liu","doi":"10.1016/j.ejphar.2025.177534","DOIUrl":"10.1016/j.ejphar.2025.177534","url":null,"abstract":"<div><h3>Objective</h3><div>Atopic dermatitis (AD) is a prevalent chronic inflammatory skin disease that significantly impacts patients' quality of life. Chlorogenic acid (CGA), a polyphenol present in various dietary sources and plants, has been shown to reduce skin inflammation. However, its efficacy and mechanisms of action in AD have not been thoroughly investigated. This study aimed to evaluate the therapeutic effect of CGA on AD in mice and explored its mechanism.</div></div><div><h3>Methods</h3><div>To establish a BALB/c mouse model of AD induced by 2,4-dinitrochlorobenzene (DNCB) to evaluate the therapeutic potential of CGA. The anti-inflammatory effects of CGA were assessed by measuring IL-1β and IL-6 levels in TNF-α-stimulated HaCaT cells. The phosphorylation levels of PI3K, Akt, Akt1, NF-κB, and IκB-α were analyzed using Western blotting. Molecular docking was conducted to evaluate the binding affinity of CGA to Akt1.</div></div><div><h3>Results</h3><div>Topical application of CGA significantly reduced dermatitis scores, spleen index, epidermal thickness, mast cell infiltration, and skin fibrosis. CGA reversed DNCB-induced increases in IgE, histamine, TNF-α, IL-1β, IL-6, and IL-8 levels. Western blot analysis showed that CGA inhibited the PI3K/Akt and NF-κB signaling pathways. <em>In vitro</em>, CGA exerts its anti-inflammatory effects by inhibiting the Akt1/NF-κB pathway, and the Akt activator (SC79) can counteract this effect. Molecular docking and dynamics simulations suggest that CGA may inhibit Akt1 activity by interacting with specific residues (ALA-50, GLY-37, TYR-326, ASP-323).</div></div><div><h3>Conclusions</h3><div>CGA improves AD by inhibiting the Akt1/NF-κB pathway, suggesting its potential as a natural treatment for AD.</div></div>","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":"998 ","pages":"Article 177534"},"PeriodicalIF":4.2,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143673707","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}

引用次数: 0

Modulation of intestinal signal transduction pathways: Implications on gut health and disease 肠道信号转导途径的调节：对肠道健康和疾病的影响。

IF 4.2 3区医学

European journal of pharmacology Pub Date : 2025-03-19 DOI: 10.1016/j.ejphar.2025.177531

Muskan Verma, Manika Garg, Pawan Yadav, Aiysha Siddiq Khan, Saman Saim Rahman, Asghar Ali, Mohan Kamthan

{"title":"Modulation of intestinal signal transduction pathways: Implications on gut health and disease","authors":"Muskan Verma, Manika Garg, Pawan Yadav, Aiysha Siddiq Khan, Saman Saim Rahman, Asghar Ali, Mohan Kamthan","doi":"10.1016/j.ejphar.2025.177531","DOIUrl":"10.1016/j.ejphar.2025.177531","url":null,"abstract":"<div><div>The gastrointestinal (GI) tract is essential for nutrient absorption and protection against pathogens and toxins. Its epithelial lining undergoes continuous renewal every 3–5 days, driven by intestinal stem cells (ISCs). ISCs are primarily of two types: actively proliferating crypt base columnar cells (CBCs), marked by Lgr5 expression, and quiescent label-retaining cells (+4 LRCs), which act as reserves during stress or injury. Key signaling pathways, such as Wnt/β-catenin, Notch, bone morphogenetic proteins (BMPs), and epidermal growth factor (EGF), are crucial in maintaining epithelial homeostasis. These pathways regulate ISCs proliferation and their differentiation into specialized epithelial cells, including goblet cells, paneth cells, enteroendocrine cells, and enterocytes. Disruptions in ISCs signaling can arise from extrinsic factors (e.g., dietary additives, heavy metals, pathogens) or intrinsic factors (e.g., genetic mutations, metabolic changes). Such disruptions impair tight junction integrity, induce inflammation, and promote gut dysbiosis, often perpetuating a cycle of intestinal dysfunction. Chronic ISCs dysregulation is linked to severe intestinal disorders, including colorectal cancer (CRC) and inflammatory bowel disease (IBD). This review emphasizes the critical role of ISCs in maintaining epithelial renewal and how various factors disrupt their signaling pathways, jeopardizing intestinal health and contributing to diseases. It also underscores the importance of protecting ISCs function to mitigate the risk of inflammation-related disorders. It highlights how understanding these regulatory mechanisms could guide therapeutic strategies for preserving GI tract integrity and treating related conditions.</div></div>","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":"998 ","pages":"Article 177531"},"PeriodicalIF":4.2,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143673714","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}

引用次数: 0

A novel adenosine 2A receptor antagonist HZ-086 enhances the efficiency of immunotherapy and alleviates the acquired resistance to PD-L1 by restoration of T cell functions

IF 4.2 3区医学

European journal of pharmacology Pub Date : 2025-03-19 DOI: 10.1016/j.ejphar.2025.177535

Pengyan Wang , Wen Ding , Jianshan Mo , Chenxi Gu , Shumin Ouyang , Keren Peng , Qiyi Zhang , Guopin Liu , Jinjian Lu , Yandong Wang , Wenhao Hu , Kai Zhu , Xiaolei Zhang

{"title":"A novel adenosine 2A receptor antagonist HZ-086 enhances the efficiency of immunotherapy and alleviates the acquired resistance to PD-L1 by restoration of T cell functions","authors":"Pengyan Wang , Wen Ding , Jianshan Mo , Chenxi Gu , Shumin Ouyang , Keren Peng , Qiyi Zhang , Guopin Liu , Jinjian Lu , Yandong Wang , Wenhao Hu , Kai Zhu , Xiaolei Zhang","doi":"10.1016/j.ejphar.2025.177535","DOIUrl":"10.1016/j.ejphar.2025.177535","url":null,"abstract":"<div><div>Immunotherapy faces significant challenges due to low clinical response rates and immune escape mechanisms, which ultimately lead to drug resistance. Previous studies suggest that adenosine-2A receptor (A<sub>2A</sub>R) signaling plays a critical role in immunosuppression and immune escape. However, no potent and selective A<sub>2A</sub>R inhibitors are currently available for clinical use to address immunotherapy resistance in tumors. In this study, we identified a novel small molecule compound, HZ-086, as a potent and selective inhibitor of A<sub>2A</sub>R. HZ-086 restored the activation of T-cell signaling which is suppressed by adenosine analogs <em>in vitro</em>. Additionally, HZ-086 enhanced T-cell-mediated cytotoxicity, increased the secretion of cytokines for antitumor and subsequently inhibited growth of tumor cells <em>in vitro</em> and <em>in vivo</em>. Furthermore, HZ-086 inhibited tumor growth, enhances anti-tumor capacity, and reversed PD-L1 resistance <em>in vivo</em>. When combined with FD-L1, a PD-L1 small molecule inhibitor discovered by our lab, HZ-086 achieved over 80 % tumor growth inhibition (TGI) and restored immune response in anti-PD-L1 monoclonal antibody-resistant tumors. This combination treatment also promoted the infiltration and activation of CD8<sup>+</sup> T lymphocytes within the tumor microenvironment. Our findings demonstrate that adenosine-A<sub>2A</sub>R signaling mediates resistance to immunotherapy and discover a novel potent and selective A<sub>2A</sub>R inhibitor with high efficacy in enhancing antitumor immune responses and reversing PD-L1 resistance. The combination of A<sub>2A</sub>R inhibitor and PD-L1 inhibitor represents a promising therapeutic strategy for antitumor therapy.</div></div>","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":"997 ","pages":"Article 177535"},"PeriodicalIF":4.2,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143673701","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}

引用次数: 0

Steroid constituents of Solidago canadensis alleviate LPS-induced inflammation via AMPK regulated mitophagy/NLRP3 and NF-κB pathway

IF 4.2 3区医学

European journal of pharmacology Pub Date : 2025-03-18 DOI: 10.1016/j.ejphar.2025.177512

Wenying Yin , Han Xue , Yongqi Zhang , Rongxian Li , Mengjia Liu , Hongwei Yue , Di Ge , Na Liu

{"title":"Steroid constituents of Solidago canadensis alleviate LPS-induced inflammation via AMPK regulated mitophagy/NLRP3 and NF-κB pathway","authors":"Wenying Yin , Han Xue , Yongqi Zhang , Rongxian Li , Mengjia Liu , Hongwei Yue , Di Ge , Na Liu","doi":"10.1016/j.ejphar.2025.177512","DOIUrl":"10.1016/j.ejphar.2025.177512","url":null,"abstract":"<div><div>Inflammation is a major risk factor for a variety of human diseases, such as sepsis, Inflammatory Bowel Disease (IBD) and also major cardiovascular disease including atherosclerosis. <em>Solidago canadensis</em> is used as a traditional medicine to treat inflammation-related diseases. However, the component with anti-inflammatory activity of <em>Solidago canadensis</em> is not clear. In this study, we aimed to search for new bioactive steroids from <em>Solidago canadensis</em> and investigate their anti-inflammatory activity both in vitro and in vivo. Lipopolysaccharides (LPS)-stimulated RAW264.7 cells, mouse bone marrow-derived macrophages (BMDMs) and peripheral blood mononuclear cells (PBMCs) were used to induce an inflammation response. Compound <strong>10</strong> outperformed other compounds for superior anti-inflammatory activity and significant inhibition of NLR family, pyrin domain containing 3 (NLRP3) inflammasome activation. Mechanistically, compound <strong>10</strong> induced mitophagy by activating AMP-activated protein kinas (AMPK) to suppress NLRP3 inflammasome activation. Inhibiting AMPK by inhibitor BML-275 significantly attenuated compound <strong>10</strong> induced mitophagy and subsequent the NLRP3 inflammasome. Besides, the NF-κB activation, key step in NLRP3 inflammasome priming, was also suppressed by compound <strong>10</strong> via activation of AMPK. In addition, the in vivo experiments showed that compound <strong>10</strong> could alleviate LPS-induced inflammatory and dextran sulfate sodium salt -induced colitis in C57BL/6 mice. Collectively, the present study, for the first time, shows that the steroids compound <strong>10</strong> exhibited anti-inflammatory effect via AMPK/mitophagy/NLRP3 as well as AMPK/NF-κB/NLRP3 signaling pathway, which strongly suggests the therapeutic potential of compound <strong>10</strong> in various inflammatory diseases.</div></div>","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":"998 ","pages":"Article 177512"},"PeriodicalIF":4.2,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143669353","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}

引用次数: 0

Skullcapflavone II induces G2/M phase arrest in hepatic stellate cells and suppresses hepatic fibrosis

IF 4.2 3区医学

European journal of pharmacology Pub Date : 2025-03-18 DOI: 10.1016/j.ejphar.2025.177522

Guoyi Rong , Jun Liu , Yunheng Yang , Shang Wang , Wenfu Cao

{"title":"Skullcapflavone II induces G2/M phase arrest in hepatic stellate cells and suppresses hepatic fibrosis","authors":"Guoyi Rong , Jun Liu , Yunheng Yang , Shang Wang , Wenfu Cao","doi":"10.1016/j.ejphar.2025.177522","DOIUrl":"10.1016/j.ejphar.2025.177522","url":null,"abstract":"<div><h3>Research purpose</h3><div>This investigation explored the therapeutic effects and mechanisms of Skullcapflavone II in hepatic fibrosis (HF).</div></div><div><h3>Materials and methods</h3><div>The optimal concentration of Skullcapflavone II for LX2 hepatic stellate cells was determined using the CCK8 assay. EdU staining and flow cytometry were utilised to assess cell proliferation and G2/M phase arrest. Mice with carbon tetrachloride-triggered HF were administered Skullcapflavone II at low (15 mg/day), medium (30 mg/day), and high (60 mg/day) doses. Subsequently, hepatic damage and fibrosis were assessed via body weight, liver index, biochemical markers, and histopathological staining. Immunohistochemistry for Collagen I and α-SMA were utilised to examine hepatic stellate cell (HSC) activation. RNA sequencing was utilised to ascertain differentially expressed genes. Molecular docking simulated interactions among Skullcapflavone II and target proteins as well as outcomes were validated by implementing western blotting, immunohistochemistry, and RT-qPCR.</div></div><div><h3>Results</h3><div>Skullcapflavone II inhibited LX2 cell proliferation and triggered G2/M phase arrest. Its optimal intervention concentration was 160 μM. <em>In vivo</em>, it ameliorated hepatic function, diminished serum indicators of fibrosis, and suppressed HSC activation. Diminished collagen sediment was validated utilising histopathological examination, whereas immunohistochemistry indicated decreased expression of Collagen I and α-SMA. Additionally, molecular docking showed strong binding of Skullcapflavone II to DNA replication-related proteins. Western blotting and RT-qPCR implied that Skullcapflavone II disrupted DNA replication, which triggered G2/M arrest and hindered HSCs activation and proliferation.</div></div><div><h3>Conclusion</h3><div>The abovementioned mechanisms of action of Skullcapflavone II substantiate its prospective clinical application against HF.</div></div>","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":"998 ","pages":"Article 177522"},"PeriodicalIF":4.2,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143669348","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}

引用次数: 0

Protein kinase-mediated inhibition of autophagy by palmitic acid in hepatocytes

IF 4.2 3区医学

European journal of pharmacology Pub Date : 2025-03-18 DOI: 10.1016/j.ejphar.2025.177528

Yeon Jeong Kim , Jae Rim Lee , Myeong Ryeo Kim , Jin Ah Jeong , Jung Ju Kim , Kwang Won Jeong

{"title":"Protein kinase-mediated inhibition of autophagy by palmitic acid in hepatocytes","authors":"Yeon Jeong Kim , Jae Rim Lee , Myeong Ryeo Kim , Jin Ah Jeong , Jung Ju Kim , Kwang Won Jeong","doi":"10.1016/j.ejphar.2025.177528","DOIUrl":"10.1016/j.ejphar.2025.177528","url":null,"abstract":"<div><div>Steatosis is characterized by an increase in free fatty acids, such as palmitic acid (PA), in hepatocytes and the accumulation of triglycerides in the liver. However, the role of intracellular autophagy in PA accumulation-induced hepatotoxicity is not clearly understood. Therefore, in this study, we investigated the effects of PA on autophagy in hepatocytes and its underlying mechanism of action. Treatment of HepG2 cells with PA induced a significant increase in intracellular p62 and LC3-II levels, suggesting inhibition of autophagy. Furthermore, PA inhibited autophagic flux in HepG2 cells, as monitored using GFP-RFP-LC3. Mechanistically, PA increased the phosphorylation of the Ser12 and Thr29 residues of LC3, which are autophagy inhibition markers, through protein kinase A (PKA) and protein kinase C (PKC) signaling. Finally, PKA and PKC inhibitors restored PA-induced autophagic flux inhibition, reduced intracellular lipid accumulation, and rescued the altered expression of lipogenic genes, such as <em>SREBP-1c</em>, in HepG2 cells. Thus, our study demonstrates the mechanism of autophagy inhibition by PA in hepatocytes and provides a potential therapeutic approach for preventing and treating hepatic steatosis.</div></div>","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":"998 ","pages":"Article 177528"},"PeriodicalIF":4.2,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143669326","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}

引用次数: 0

Alterations of gut microbiota for the onset and treatment of psoriasis: A systematic review

IF 4.2 3区医学

European journal of pharmacology Pub Date : 2025-03-17 DOI: 10.1016/j.ejphar.2025.177521

Man Xue , QuanWen Deng , Li Deng , TianRong Xun , TingTing Huang , JingQian Zhao , Sui Wei , ChenYu Zhao , Xi Chen , YiWen Zhou , YanHua Liang , XiXiao Yang

{"title":"Alterations of gut microbiota for the onset and treatment of psoriasis: A systematic review","authors":"Man Xue , QuanWen Deng , Li Deng , TianRong Xun , TingTing Huang , JingQian Zhao , Sui Wei , ChenYu Zhao , Xi Chen , YiWen Zhou , YanHua Liang , XiXiao Yang","doi":"10.1016/j.ejphar.2025.177521","DOIUrl":"10.1016/j.ejphar.2025.177521","url":null,"abstract":"<div><div>Psoriasis is a chronic, recurrent and systemic inflammatory skin disease which is mediated by immunoreaction. Its pathogenesis is multifactorial, and the exact driving factor remains unclear. Recent studies showed that gut microbiota, which maintain immune homeostasis of our bodies, is closely related with occurrence, development and prognosis of psoriasis. The intestinal microbial abundance and diversity in patients with psoriasis have changed significantly, including intestinal microbiota disorders and reduced production of short chain fatty acids (SCFAs), abnormalities in Firmicutes/Bacteroidetes (F/B), etc. Besides, the intestinal microbiota of psoriasis patients has also changed after treatment of systemic drugs, biologics and small molecule chemical drugs, suggesting that the intestinal microbiota may be a potential response-to-treatment biomarker for evaluating treatment effectiveness. Oral probiotics and prebiotics administration as well as fecal microbial transplantation were also reported to benefit well in psoriasis patients. Additionally, we also discussed the microbial changes from the skin and other organs, which regulated both the onset and treatment of psoriasis together with gut microbiota. Herein, we reviewed recent studies on the psoriasis-related microbiota in an attempt to confidently identify the “core” microbiota of psoriatic patients, understand how microbiota influence psoriasis through the gut-skin axis, and explore potential therapeutic strategies for psoriasis.</div></div>","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":"998 ","pages":"Article 177521"},"PeriodicalIF":4.2,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143663049","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}

引用次数: 0

The potential neuroprotective effect of empagliflozin against depressive-like behavior induced by chronic unpredictable mild stress in rats: Involvement of NLRP3 inflammasome

IF 4.2 3区医学

European journal of pharmacology Pub Date : 2025-03-17 DOI: 10.1016/j.ejphar.2025.177525

Marwa A. Ali, Haidy E. Michel, Esther T. Menze, Marianne G. Tadros, Sara A. Wahdan

{"title":"The potential neuroprotective effect of empagliflozin against depressive-like behavior induced by chronic unpredictable mild stress in rats: Involvement of NLRP3 inflammasome","authors":"Marwa A. Ali, Haidy E. Michel, Esther T. Menze, Marianne G. Tadros, Sara A. Wahdan","doi":"10.1016/j.ejphar.2025.177525","DOIUrl":"10.1016/j.ejphar.2025.177525","url":null,"abstract":"<div><div>Depression is a prevalent and debilitating condition that has a severe negative impact on a person's life. Chronic stress exposure plays a substantial role in the development of depression. In the present study, rats were exposed to chronic unpredictable mild stress (CUMS) for four weeks. Empagliflozin (EMPA), a Sodium-Glucose Cotransporter-2 (SGLT-2) inhibitor, is an oral antidiabetic agent exhibiting antioxidant, anti-inflammatory, and antiapoptotic effects. This study aimed to examine the antidepressant effect of EMPA in an experimental animal model of depression induced by CUMS in rats and explore the probable underlying mechanisms. Rats were treated with EMPA, per-orally, at a dose of 10 mg/kg/day for four weeks. EMPA treatment counteracted CUMS-induced histopathological, biochemical and behavioral alterations. EMPA suppressed the CUMS-induced increase in the oxidative stress, inflammatory, and apoptotic markers, where levels of MDA, IL-1β, TNF-α, NF-κB, NLRP3 and active caspase 3 were reduced by 29.6 %, 24.8 %, 17.9 %, 36.6 %, 24.5 % and 41.5 %, respectively, compared to the disease group. Furthermore, EMPA decreased the level of the microglial activation marker, iba-1 by 24 % in comparison to the disease group. In addition, EMPA treatment decreased blood glucose levels by 39 %, decreased serum insulin levels by 60.6 %, decreased HOMA-IR by 76.5 % and increased GLUT 4 expression, compared to the CUMS group, all which proves that EMPA has an effect insulin signaling and alleviates insulin resistance. Our results conclude that modulating key factors involved in depression, such as inflammation, oxidative stress, and NLRP3 inflammasome pathway, accounts for the anti-depressant effect of EMPA.</div></div>","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":"998 ","pages":"Article 177525"},"PeriodicalIF":4.2,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143663098","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}

引用次数: 0

Auranofin-loaded chitosan-lipid hybrid nanoparticle protects against rotenone model of Parkinson's disease via modulation of GSK-3β/ Nrf2/HO-1 signaling

IF 4.2 3区医学

European journal of pharmacology Pub Date : 2025-03-17 DOI: 10.1016/j.ejphar.2025.177523

Divya Soni , Yogesh Garg , Shubham Upadhayay , Amit Bhatia , Bushra Basir , Sachin Kumar Singh , Kamal Dua , Puneet Kumar

{"title":"Auranofin-loaded chitosan-lipid hybrid nanoparticle protects against rotenone model of Parkinson's disease via modulation of GSK-3β/ Nrf2/HO-1 signaling","authors":"Divya Soni , Yogesh Garg , Shubham Upadhayay , Amit Bhatia , Bushra Basir , Sachin Kumar Singh , Kamal Dua , Puneet Kumar","doi":"10.1016/j.ejphar.2025.177523","DOIUrl":"10.1016/j.ejphar.2025.177523","url":null,"abstract":"<div><div>Auranofin (AUF) is a gold-based compound that has demonstrated a wide range of biological effects, such as anti-inflammatory and antibacterial effects. However, the neuronal use of AUF is restricted due to its low bioavailability. Thus, to improve blood brain barrier (BBB) penetration and investigate its antiparkinsonian impact, the researchers developed AUF-loaded hybrid nanoparticles (AUFHNPs). This research delves into the neuroprotective potential of AUFHNPs against rotenone-induced Parkinson's disease (PD). The MTT assay, Acridine orange/Ethidium bromide (AO/EB) staining, RT-PCR, and Western blot analysis were performed on SH-SY5Y lines. Also, AUFHNPs were prepared and characterized. For the <em>in-vivo</em> study, AUF, its NPs and rotenone were administered for 28 days, and behavioral parameters were performed on day 27 and 28. On the 29th day, animals were sacrificed, and brains were isolated for biochemical assessment, apoptotic and inflammatory markers evaluation, histopathology, and molecular examination. <em>In-vitro</em> results showed that AUF significantly restored cell viability and reduced apoptosis. Spherical-shaped NPs were observed under FE-SEM/TEM analysis. Administration of AUFHNPs in rats significantly restored motor activity and neuronal morphological changes by phosphorylating GSK-3β to increase the expression of Nrf2/HO-1. This study concludes that developing AUFHNPs increases AUF's bioavailability in the brain and exerts neuroprotection via modulating GSK-3β/Nrf2/HO-1 pathways.</div></div>","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":"998 ","pages":"Article 177523"},"PeriodicalIF":4.2,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143663052","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}

引用次数: 0