Current pharmaceutical design最新文献

{"title":"Targeting Anaplastic Lymphoma Kinase in Oncology: Identification and Computational Validation of Novel Inhibitors for Anaplastic Large Cell Lymphoma, Non-small Cell Lung Cancer, and Neuroblastoma.","authors":"Aftab Alam, Mohammed H Alqarni, Indrakant K Singh, Ahmed I Foudah, Neeraj Upmanyu, Mohamed F Balaha","doi":"10.2174/0113816128342778250218105338","DOIUrl":"https://doi.org/10.2174/0113816128342778250218105338","url":null,"abstract":"<p><strong>Background: </strong>Anaplastic Lymphoma Kinase (ALK) is implicated in several cancers, including anaplastic large cell lymphoma, non-small cell lung cancer, and neuroblastoma. Targeted inhibition of ALK represents a promising therapeutic strategy.</p><p><strong>Aims: </strong>This study aimed to identify and evaluate potential ALK inhibitors using virtual screening and computational analyses to determine their binding stability, affinity, and dynamic behavior, ultimately assessing their potential as therapeutic agents for ALK-driven cancers.</p><p><strong>Objective: </strong>The objective of this study was to identify potential ALK inhibitors using virtual screening techniques and to evaluate their binding affinities and stability through computational analyses.</p><p><strong>Methods: </strong>This study utilized virtual screening to identify potential ALK inhibitors from the MTiOpen Screen Diverse library and selected three compounds (24331480, 26536128, and 24353407) based on their binding affinities. These compounds underwent optimization using Density Functional Theory (DFT) and were redocked to confirm binding stability. Molecular dynamics simulations, hydrogen bond analysis, MM/PBSA calculations, and PCA-based free energy landscape analysis were also carried out.</p><p><strong>Results: </strong>The re-docking experiments confirmed the stable and strong binding affinities of the selected compounds to the ALK active site. Molecular dynamics simulations revealed stable interactions throughout the 200 ns simulation period. Hydrogen bond analysis demonstrated consistent hydrogen bonds between key residues and the inhibitors. MM/PBSA calculations indicated favorable binding free energies, suggesting strong binding affinities. Finally, PCA-based free energy landscape analysis highlighted energetically favorable binding modes.</p><p><strong>Conclusion: </strong>The identified compounds (24331480, 26536128, and 24353407) exhibited promising inhibitory potential against ALK. These findings warrant further experimental validation to confirm their potential as therapeutic agents for ALK-driven cancers.</p>","PeriodicalId":10845,"journal":{"name":"Current pharmaceutical design","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143604075","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pre-clinical Safety Study of Cold Atmospheric Plasma (CAP) Produced by an Inbuilt CAP Device and ROS Mediated Apoptotic Activity in Human Skin Melanoma Cells.","authors":"Ratul Chakraborty, Reetesh Borpatra Gohain, Punam Talukdar, Liza Changkakoti, Subir Biswas, Ashis K Mukherjee, Asis Bala","doi":"10.2174/0113816128335012250122221541","DOIUrl":"https://doi.org/10.2174/0113816128335012250122221541","url":null,"abstract":"<p><strong>Introduction: </strong>In recent decades, Cold Atmospheric Plasma (CAP) has become increasingly popular in healthcare for managing diseases, especially skin cancer. This study aimed to assess the preclinical safety of an indigenously developed dielectric barrier discharge-CAP device and its cytotoxic efficacy against melanoma cells while adhering to OECD 402 guidelines for acute dermal toxicity study. The safety evaluation includes ex vivo studies on mouse peritoneal exudates and in vivo acute dermal toxicity tests on Wistar rats.</p><p><strong>Methods: </strong>The ex vivo study of mice peritoneal cells treated for up to 120 seconds, showed a survival rate of over 90% up to 90 seconds of CAP treatment for applied voltage 18.6 kV at 20 kHz with no significant difference with control. In the acute dermal toxicity tests, CAP exposure for up to 30 seconds caused minimal inflammatory cell infiltration and no significant Dermal Inflammation Scoring (DIS) (<1).</p><p><strong>Results: </strong>The efficacy study against G361 human melanoma cells showed reduced cell viability by ~50% (MTT assay) upon 30 seconds of CAP treatment for applied voltage 24 kV at 20 kHz through ROS-mediated apoptosis, confirmed by a 3-fold increase in intracellular reactive oxygen species levels and nuclear fragmentation (4',6-diamidino-2-phenylindole staining). Annexin V/PI (propium iodide) staining further revealed ~30% apoptosis after 24 hours of incubation. These findings establish the developed DBD-CAP device is safe for rat skin exposure durations of up to 30 seconds and effective in inducing apoptosis in melanoma cells.</p><p><strong>Conclusion: </strong>This study supports CAP's optimization for clinical applications and its integration with existing therapies for enhanced outcomes. However, further study is needed to examine the possible risks associated with using CAP devices in the biomedical field.</p>","PeriodicalId":10845,"journal":{"name":"Current pharmaceutical design","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143604072","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Mini-Review on EGFR-Tyrosine Kinase Inhibitors and their Resistance Mechanisms.","authors":"Mohd Javed Naim, Abdul Samad","doi":"10.2174/0113816128349342250121053445","DOIUrl":"https://doi.org/10.2174/0113816128349342250121053445","url":null,"abstract":"<p><strong>Background: </strong>An essential component of cell development, proliferation, and survival is the transmembrane receptor known as the epidermal growth factor receptor (EGFR). Dysregulated EGFR signalling is an appealing pathway that has been linked to the genesis and progression of several cancer types. EGFR tyrosine kinase inhibitors (TKIs) are targeted drugs that show promise in the fight against cancer. EGFR tyrosine kinase inhibitors obstruct cancer growth and survival signalling pathways by blocking the receptor's tyrosine kinase domain. Patients with non-small cell lung cancer (NSCLC) that have EGFR mutations have shown increased progression-free survival and overall survival rates when treated with EGFR TKIs as compared to conventional chemotherapy, according to many clinical studies.</p><p><strong>Objectives: </strong>This review is aimed to present the journey of EGFR-tyrosine kinase inhibitors, their signalling cascade, and various resistant mechanisms.</p><p><strong>Methods: </strong>The literature search was carried out on electronic databases like PubMed, Medline, etc., by employing search keywords, such as EGFR, EGFR inhibitors, cancer, tyrosine kinase, etc., and data on EGFR signaling pathways and the types of potential inhibitors in a hierarchical manner, followed by various resistance mechanisms that have emerged, were collected.</p><p><strong>Results: </strong>Drug resistance is still an issue in long-term therapy of patients, even though EGFR TKIs provide substantial therapeutic advantages. Common routes of resistance to EGFR TKIs include acquired resistance mechanisms, which include the development of secondary EGFR mutations and the activation of alternative signalling pathways. To improve the therapeutic effectiveness of EGFR TKIs, future research will center on searching indicators of response and resistance, finding ways to employ these medicines most effectively, and creating new treatment approaches.</p><p><strong>Conclusion: </strong>This review provides insight into the use of EGFR kinase inhibitors for treating cancer patients and outlines potential advancements in current therapies to develop more effective molecules.</p>","PeriodicalId":10845,"journal":{"name":"Current pharmaceutical design","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143604070","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SNHG10: A Novel Long Non-coding RNA with Multifaceted Roles in Human Cancers.","authors":"Haodong He, Jingjie Yang, Yan Zhou, Lihan Chen, Chuyuan Liao, Ting Gong, Tongtong Li, Haoran Liu, Yunfei Pan, Pengbo Zhang, Xiaolan Li, Chengfu Yuan","doi":"10.2174/0113816128356231250212050707","DOIUrl":"https://doi.org/10.2174/0113816128356231250212050707","url":null,"abstract":"<p><p>Long non-coding RNAs (lncRNAs) are a type of RNA with a length of more than 200 nucleotides. They do not encode proteins but are crucial in regulating gene expression and affecting the malignant biological behavior of cancer. Small nucleolar RNA host gene 10 (SNHG10) is a novel lncRNA that plays a regulatory role in many malignant tumors. Several recent studies have shown that SNHG10 is aberrantly expressed in various forms of cancer. This instability is closely related to important tumorigenic processes, such as cell proliferation, migration, invasion, epithelial-mesenchymal transition (EMT), and chemotherapy resistance. SNHG10 has been reported to play a role through a variety of molecular mechanisms, including serving as a competing endogenous RNA (ceRNA), regulating epigenetic processes, and affecting immune responses and tumor microenvironment. Furthermore, SNHG10 is involved in metabolic reprogramming, immune evasion, and chromatin remodeling, highlighting its diverse roles in tumor biology. Due to the specificity and selectivity of its expression level, the potential of SNHG10 as a diagnostic biomarker and therapeutic target has attracted significant attention, and its correlation with the prognosis and treatment of various tumor types is of great significance. This review focuses on the biological function and molecular mechanism of SNHG10 and its relationship with various malignant tumors. In addition, this review highlights the potential of SNHG10 to improve precision oncology and develop novel cancer therapies by investigating its upstream regulators, downstream targets, and interactions with nuclear and cytoplasmic processes.</p>","PeriodicalId":10845,"journal":{"name":"Current pharmaceutical design","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143566402","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Recent Developments in the Synthesis of Benzothiazoles and their Anti-cancer Mechanistic Discoveries.","authors":"Wafaa A Zaghary, Galal H Elgemeie, Rasha A Azzam, Safa A Aljuhr, Tamer M Sakr","doi":"10.2174/0113816128355783250212043621","DOIUrl":"https://doi.org/10.2174/0113816128355783250212043621","url":null,"abstract":"<p><p>Benzothiazole derivatives have garnered considerable attention owing to their versatile chemical scaffold and remarkable biological activities. The article provides an in-depth analysis of the diverse structural modifications and strategies employed to enhance the anticancer potential of these compounds from the period of 2020 to 2024. It discusses the role of structure-activity relationships (SAR) and computational approaches in optimizing benzothiazole derivatives for selective and effective cancer treatment.</p>","PeriodicalId":10845,"journal":{"name":"Current pharmaceutical design","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143566399","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Molecular Mechanisms of Natural Medicinal Active Ingredients Interfering with Male Fertility.","authors":"Wen-Wen Zhao, Liu Yang, Ye-Bin Yang, Ran Guo, Xing-Sheng Xiao, Yi-Min Cheng","doi":"10.2174/0113816128356183250207105548","DOIUrl":"https://doi.org/10.2174/0113816128356183250207105548","url":null,"abstract":"<p><p>The challenges posed by excessive global population growth remain significant. Hormonal female contraceptive pills, which have been approved for over 60 years, serve as an important means of contraception; however, many women experience adverse effects after taking these pills, including abnormalities in blood clotting, dizziness, headaches, and vomiting. In this context, male contraceptives have emerged as a prominent area of research. Unfortunately, most male contraceptives are still in the experimental or clinical research stages. Therefore, screening for active ingredients that can specifically inhibit sperm function from natural drug active ingredient libraries holds substantial clinical and practical significance. In this manuscript, we review the inhibitory effects of various natural drug active monomers on sperm function and their underlying molecular mechanisms, aiming to provide theoretical insights for the future development of novel male contraceptives.</p>","PeriodicalId":10845,"journal":{"name":"Current pharmaceutical design","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143566507","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mechanistic Insights into the Role of MCP-1 in Diverse Liver Pathological Conditions: A Recent Update.","authors":"Sahil Dhengle, Krushna Ch Maharana, Sarasa Meenakshi, Sanjiv Singh","doi":"10.2174/0113816128332969241120030733","DOIUrl":"10.2174/0113816128332969241120030733","url":null,"abstract":"<p><p>Monocyte chemoattractant protein-1 (MCP-1) is regarded as a crucial proinflammatory cytokine that controls the migration and entry of macrophages. It has been demonstrated that chemokine ligand 2 and its receptor, chemokine receptor 2, are both implicated in several liver disorders. In a similar context, immunity mediators are overexpressed and stimulated by MCP-1. Additionally, MCP-1 alters the physiology of the hepatocytes, promoting immunologic and inflammatory responses beyond regular metabolism. Alcoholism and other factor including abnormal diet stimulate the liver's synthesis of MCP-1, which can result in inflammation in liver. Studies shows how MCP-1' linked to various liver disorders like alcoholic liver disease, liver fibrosis, non-alcoholic fatty liver disease, hepatitis, hepatic steatosis, hepatocellular cancer, primary biliary cirrhosis. MCP-1 not only predicts the onset, progression, and prognosis of the illness, but it is also directly related to the degree and stage of liver inflammation. In this review, we will explore the mechanism and connection between MCP-1's overexpression in liver disorders, further how it can be linked as a therapeutic biomarker in the above scenario.</p>","PeriodicalId":10845,"journal":{"name":"Current pharmaceutical design","volume":" ","pages":"1167-1179"},"PeriodicalIF":2.6,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142946090","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nutraceutical Interventions for Mitigating Skin Ageing: Analysis of Mechanisms and Efficacy.","authors":"Mohammad Ibrahim, Harpreet Singh, Mohd Fahim, Shabina Khan, Jalaluddin Khan, Jagdish Kumar Arun, Arun Kumar Mishra, Tarun Virmani, Ashwani Sharma, Girish Kumar, Dalapathi Gugulothu, Shivani Chopra, Hitesh Chopra","doi":"10.2174/0113816128336661250218080928","DOIUrl":"https://doi.org/10.2174/0113816128336661250218080928","url":null,"abstract":"<p><p>Skin ageing is influenced by intrinsic factors such as genetics and hormones, as well as extrinsic factors like environmental exposure, ultraviolet (UV) radiation, and diet. These factors lead to biochemical, biological, and structural changes in the skin. Plant-derived compounds with antioxidant and anti-inflammatory properties have emerged as potential anti-ageing agents. This comprehensive review, spanning data from 1997 to 2024, explores the role of nutraceuticals in skin anti-ageing. The research data were drawn from Google, PubMed, PubMed Central, Scopus, and various journal databases, including ScienceDirect, Springer, and Taylor & Francis. This review specifically examines plant-derived polyphenols, carotenoids, and other bioactive compounds, analysing their mechanisms through signalling pathways and cellular processes, using data from in vitro, in vivo, and clinical studies. Polyphenols like quercetin, curcumin, and epigallocatechin gallate (EGCG) have antioxidant and anti-inflammatory properties, helping to reduce oxidative stress, inflammation, UV-induced collagen degradation, and inflammatory cytokines. Notably, curcumin enhances collagen production and decreases the number of senescent cells. Carotenoids such as β-carotene, lutein, zeaxanthin, and lycopene protect against UV damage, and lycopene-rich tomato paste was specifically noted for its ability to reduce erythema and DNA damage. Additionally, compounds like resveratrol, fisetin, and wogonin exert protective effects against oxidative stress and inflammation, with resveratrol improving collagen synthesis and reducing the appearance of wrinkles. These plant-derived compounds can effectively combat skin ageing through various mechanisms, including the inhibition of oxidative stress, inflammation, and extracellular matrix degradation. They present a natural and sustainable approach to skincare in accord with the growing trend of conscious consumption. Future research should focus on understanding the long-term effects and determining the optimal dosage for clinical applications, highlighting the potential of integrating plant-based nutraceuticals into skincare regimens.</p>","PeriodicalId":10845,"journal":{"name":"Current pharmaceutical design","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143540493","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Investigation of the Effect of Rose Oxide in Animal Models of Paclitaxel-induced Neuropathic Pain in Rats.","authors":"Ana Marieta Fernandes Moreira, Boris Timah Acha, Tiberio Cesar Meneses de Oliveira Sinimbu, Suellen Aparecida Patricio Pereira, Fernanda Regina de Castro Almeida, Antonio Guilherme Silva Santos, Luciano da Silva Lopes, Anderson Nogueira Mendes, Maria de Lourdes Ferreira Meneses Dos Santos","doi":"10.2174/0113816128327126250220093640","DOIUrl":"https://doi.org/10.2174/0113816128327126250220093640","url":null,"abstract":"<p><strong>Introduction: </strong>Neuropathy caused by chemotherapy, a dose-limiting neurotoxic side effect, often leads to treatment discontinuation. About 30 to 70% of patients treated with paclitaxel experience peripheral neuropathy due to the drug combination and dosage. Given the significant prevalence of neuropathy in individuals who have undergone chemotherapy treatments and the growing need for new therapeutic approaches, including those based on natural resources, it is imperative to investigate substances capable of mitigating this adverse effect.</p><p><strong>Method: </strong>Natural plant compounds are often used to treat various pathological conditions due to superior treatment options and minimal side effects. Rose oxide (RO), monoterpenes present in several essential oils, have demonstrated anti-inflammatory activity by inhibiting IL-1β production and leukocyte migration. Therefore, the present study aimed to investigate the effect of rose oxide in its free form on animal models of neuropathic pain induced by antineoplastics in rats. Neuropathic pain was induced by paclitaxel at a dose of 20 mg/kg i.p. for four consecutive days and treated with rose oxide at doses of 12.5, 25, and 50 mg/kg and after this period, behavioral analyzes (von Frey mechanical allodynia, acetone test and open field), biochemical, hematological and assessment of oxidative stress (malondialdehyde levels). The results suggested that rose oxide has antinociceptive activity in animal models of antineoplastic-induced neuropathic pain in rats.</p><p><strong>Results: </strong>Furthermore, treatment with rose oxide did not show significant adverse effects on biochemical and hematological parameters, with the exception of the 12.5 mg/kg dose of RO affected creatinine levels and all doses of TGP, while the highest dose (50 mg/kg) caused changes in total proteins and albumin, suggesting a more binding strong with plasma proteins. Finally, treatment with RO 25 mg/kg significantly altered malondialdehyde (MDA) levels.</p><p><strong>Conclusion: </strong>These results suggest that the use of rose oxide in its free form may be a promising option for the treatment of antineoplastic-induced neuropathic pain in humans. However, further studies are needed to confirm these findings and evaluate safety and efficacy.</p>","PeriodicalId":10845,"journal":{"name":"Current pharmaceutical design","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143540491","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Esketamine Regulates Mitophagy through ULK1/FUNDC1 Signaling Pathway to Improve LPS-induced Acute Respiratory Distress Syndrome.","authors":"Mei Ding, Ping Pei, Weihua Liu, Yingli Cao, Yiqi Weng, Wenli Yu","doi":"10.2174/0113816128361112250221065359","DOIUrl":"https://doi.org/10.2174/0113816128361112250221065359","url":null,"abstract":"<p><strong>Background: </strong>As a heterogeneous clinical syndrome, acute respiratory distress syndrome (ARDS) is caused by infection-associated inflammation with limited treatment options. Esketamine possesses antiinflammatory properties, and it is effective in treating lung diseases.</p><p><strong>Objective: </strong>This study aimed to unveil the efficacy and mechanism of esketamine in ARDS.</p><p><strong>Methods: </strong>Lipopolysaccharide (LPS) is widely used to induce inflammatory response in lung injury. The mice model of ARDS in this study was established through the inhalation of LPS. Hematoxylin-eosin (H&E) staining was used to evaluate the pathological changes in the lung tissues of ARDS mice, and the histological index of lung damage was employed. Bicinchoninic acid (BCA) assay kits were utilized to assess the total proteins in bronchoalveolar lavage fluid (BALF), and a hemocytometer was used to count the number of total cells. The pulmonary vascular permeability was detected using Evans blue staining. Western blot was carried out to detect the expressions of tight junction proteins, and enzyme-linked immunosorbent assay (ELISA) detected the release of inflammatory cytokines in BALF and serum. Dihydroethidium (DHE) staining was used to detect reactive oxygen species (ROS) production, and the levels of myeloperoxidase (MPO) and oxidative stress markers were measured using corresponding assay kits. Apoptosis was assessed through terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) and Western blot. Immunostaining detected the FUN14 domain-containing 1 (FUNDC1) and light chain 3B (LC3B) in lung tissues, and the expressions of autophagy-related proteins were detected using Western blot.</p><p><strong>Results: </strong>Our data showed that esketamine treatment alleviated LPS-stimulated lung damage, improved pulmonary vascular permeability, and inhibited inflammatory response, oxidative stress, and apoptosis in ARDS mice. Mechanically, esketamine activated mitophagy through UNC-52-like kinase 1 (ULK1)/FUNDC1 signaling pathway. These findings, for the first time, revealed the therapeutic potential of esketamine in treating ARDS.</p><p><strong>Conclusion: </strong>Collectively, this study revealed the protective role of esketamine against lung injury, inflammation, oxidative stress, and apoptosis in mice with ARDS and revealed the reaction mechanism related to mitophagy.</p>","PeriodicalId":10845,"journal":{"name":"Current pharmaceutical design","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143540357","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}