Naunyn-Schmiedeberg's archives of pharmacology最新文献

{"title":"Morin, as a natural flavonoid, provides promising influences against cardiovascular diseases.","authors":"Reza Khademi, Ali Mirzaei, Amirhossein Mirzaei, Farid Reza Edjlali, Vahid Reza Askari, Vafa Baradaran Rahimi","doi":"10.1007/s00210-024-03783-4","DOIUrl":"https://doi.org/10.1007/s00210-024-03783-4","url":null,"abstract":"<p><p>The present investigation evaluated the potential impacts of morin, a natural flavonoid, against cardiovascular disorders. Since inception until September 2024, PubMed, Scopus, and Web of Science have been searched extensively. The process involved eliminating duplicate entries and conducting a systematic review of the remaining studies post-full-text screening. The search was conducted with meticulousness and in adherence to established protocols. Morin has shown various cardioprotective effects in experimental models. It reduces oxidative stress, inflammation, and tissue damage in conditions like myocardial ischemia, injury, and infarction. It also mitigates the harmful effects of toxins and improves hemodynamic parameters, antioxidant levels, and cardiac function. Moreover, it can address conditions like chronic iron overload and metabolic syndrome. Its mechanisms of action involve regulating signaling pathways, promoting autophagy, and reducing oxidative stress and inflammation. Morin hydrate is promising as a therapeutic agent for cardiovascular and related disorders. Morin Hydrate exhibits promising cardioprotective properties, effectively reducing oxidative stress and inflammation in myocardial conditions while also countering the effects of toxins and improving heart function. Additionally, it holds the potential for addressing chronic iron overload and metabolic syndrome. Its multifaceted mechanisms, including signaling pathway regulation and promotion of autophagy, highlight its therapeutic potential for various cardiovascular and related disorders.</p>","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142979230","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":"Exploring the impact of cuproptosis-related genes on immune infiltration in rheumatoid arthritis.","authors":"Fang Xu, Xin-Ran Hu, Yuan Wang, Xi-Fan Mei","doi":"10.1007/s00210-024-03731-2","DOIUrl":"https://doi.org/10.1007/s00210-024-03731-2","url":null,"abstract":"<p><p>Immune infiltration plays a significant role in the pathogenesis of rheumatoid arthritis (RA). Cuproptosis, a newly characterized form of programmed cell death, remains insufficiently investigated regarding its genetic regulation of immune infiltration in RA. Data from the GEO database were analyzed to determine the relationship between cuproptosis-related genes and immune infiltration. Comprehensive analyses, including Gene Ontology, and KEGG pathway enrichment were performed to construct a risk model and provide a theoretical framework for understanding the mechanisms underlying the involvement of cuproptosis in RA-related immune infiltration. And we explored the expression of related genes-PDHB in animal and cell experiments. The findings revealed substantial variations in immune infiltration between RA and control groups. Eleven cuproptosis-related genes associated with RA were identified, namely DLST, LIAS, DLAT, DLD, PDHB, Lipt1, DBT, ATP7B, SLC31A1, FDX1, and PDHA1. Among these, DLST and PDHB emerged as potential risk factors influencing RA pathogenesis. These genes modulated immune cell alterations, including changes in iDCs, NK-cells, mast cells, and pDCs, alongside impacts on immune functions specific to RA. In animal experiments, we found that the expression of PDHB is decreased; overexpression of PDHB by PDHB gene transfection inhibited the migration, invasion, and proliferation of FLS cells.</p>","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142971663","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":"Marine-derived bioactive compounds for neuropathic pain: pharmacology and therapeutic potential.","authors":"Swapnil Mishra, Yogesh Mishra, Ashutosh Kumar","doi":"10.1007/s00210-024-03667-7","DOIUrl":"https://doi.org/10.1007/s00210-024-03667-7","url":null,"abstract":"<p><p>Neuropathic pain, a challenging condition often associated with diabetes, trauma, or chemotherapy, impairs patients' quality of life. Current treatments often provide inconsistent relief and notable adverse effects, highlighting the urgent need for safer and more effective alternatives. This review investigates marine-derived bioactive compounds as potential novel therapies for neuropathic pain management. Marine organisms, including fungi, algae, cone snails, sponges, soft corals, tunicates, and fish, produce a diverse range of secondary metabolites with significant pharmacological properties. These include peptides (e.g., conopeptides, piscidin 1), non-peptides (e.g., guanidinium toxins, astaxanthin, docosahexaenoic acid, fucoidan, apigenin, fumagillin, aaptamine, flexibilide, excavatolide B, capnellenes, austrasulfones, lemnalol), and crude extracts (e.g., Spirulina platensis, Dunaliella salina, Cliothosa aurivilli). These compounds exhibit diverse mechanisms of action, such as modulating ion channels (e.g., transient receptor potential channels, voltage-gated sodium, calcium, and potassium channels, and G protein-coupled inwardly rectifying potassium channels), interacting with cell-surface receptors (e.g., nicotinic acetylcholine, NMDA, kainate, GABA_B​, and neurotensin receptors), inhibiting norepinephrine transporters, reducing oxidative stress, and attenuating neuroinflammation. These effects collectively contribute to alleviating nerve degeneration and symptoms of neuropathic pain, including hyperalgesia, allodynia, and associated psychomotor disturbances. Marine-derived bioactive compounds represent promising alternatives to conventional neuropathic pain treatments, to advance their development and assess their integration into neuropathic pain management strategies.</p>","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142965816","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":"Suppressing the progression of bladder cancer using cyclovirobuxine D based on network pharmacology and bioinformatics approaches.","authors":"Ke Gao, Hanbing Jiang, Chao Zhang, Lin Li, Yuhong Qi, Nan Yang, Xiaoshun Li, Yongshun Wang, Bin Wu, Qiuju Shao, Guojun Wu","doi":"10.1007/s00210-024-03754-9","DOIUrl":"https://doi.org/10.1007/s00210-024-03754-9","url":null,"abstract":"<p><p>Limited treatment options are available for bladder cancer (BCa) resulting in extremely high mortality rates. Cyclovirobuxine D (CVB-D), a naturally alkaloid, reportedly exhibits notable antitumor activity against diverse tumor types. However, its impact on CVB-D on BCa and its precise molecular targets remain unexplored. This study conducts CCK8 assay, colony formation assay, and flow cytometry experiments to demonstrate that CVB-D inhibits long-term proliferation and viability of BCa cell lines, thereby inducing apoptosis in vitro. It employs PPI networks and the CytoHubba algorithm to identify COL1A1, COL6A1, COL6A2, COL5A2, COL5A1, COL12A1, COL18A1, ITGA5, VCL, FLNA, and GSN as crucial therapeutic targets for CVB-D that can halt the malignant progression of BCa. GO and KEGG analyses indicate that the PI3K/AKT signaling pathway potentially may play a pivotal role in mediating the anti-BCa growth effects of CVB-D. The ROC curve and K-M survival analyses reveal the significant clinical value of all the 11 identified therapeutic targets, with GSN as the most effective target of CVB-D in combating BCa. This study also uncovers a potential interaction between GSN and CVB-D through molecular docking and molecular dynamics simulations. RT-qPCR and Western blotting experiments provide further evidence that CVB-D effectively suppresses GSN mRNA and protein expression in a concentration-dependent fashion. Our comprehensive study is the first report on the molecular mechanism of CVB-D against BCa, identifying GSN as a pivotal target in CVB-D-based anti-BCa therapy. We believe that our study results may help establish a theoretical basis for the possible utilization of CVB-D in cancer therapeutics.</p>","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142965860","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":"Sexual dysfunctions associated with antipsychotic drug intake: a retrospective analysis of the FDA adverse events reporting system (FAERS).","authors":"Johanna Engel, Lamin Jeridi, Lilly Auerbach, Oliver Zolk, Timo Greiner, Martin Heinze, Pichit Buspavanich, Michael Schneider","doi":"10.1007/s00210-024-03763-8","DOIUrl":"https://doi.org/10.1007/s00210-024-03763-8","url":null,"abstract":"<p><p>Sexual dysfunctions (SD) are common and debilitating side effects of antipsychotics. The current study analyzes the occurrence of antipsychotic-related SD using data from the US Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS). FAERS was queried for sexual dysfunction adverse events (encoded by 35 different MedDRA preferred terms) secondary to amisulpride, aripiprazole, chlorprothixene, clozapine, haloperidol, loxapine, olanzapine, pipamperone, quetiapine, risperidone, and ziprasidone from 2000 to 2023. Disproportionality signal analysis was performed by calculating the reporting odds ratio (ROR) with its 95% confidence interval (CI). During the observation period, 9203 cases of SD were reported in association with the antipsychotic drug use. Men reported these dysfunctions more frequently (68.4% of all cases) than women. Ziprasidone had the highest ROR for sexual dysfunction in FAERS, at <math><mrow><mn>84.86</mn> <mo>;</mo> <mn>95</mn> <mo>%</mo> <mspace></mspace> <mi>C</mi> <mi>I</mi> <mspace></mspace> <mo>(</mo> <mn>77.50</mn> <mo>,</mo> <mspace></mspace> <mn>92.94</mn> <mo>)</mo> <mo>)</mo></mrow> </math> , followed by aripirazole for sexual dysfunction <math><mrow><mo>(</mo> <mi>R</mi> <mi>O</mi> <mi>R</mi> <mo>=</mo> <mn>34.17</mn> <mo>;</mo> <mn>95</mn> <mo>%</mo> <mspace></mspace> <mi>C</mi> <mi>I</mi> <mspace></mspace> <mo>(</mo> <mn>32.06</mn> <mo>,</mo> <mspace></mspace> <mn>36.43</mn> <mo>)</mo> <mo>)</mo></mrow> </math> . In general, aripiprazole, olanzapine, risperidone, ziprasidone, and quetiapine had higher risk signals across multiple adverse events (AEs), whereas chlorprothixene, loxapine, and amisulpride showed lower risk signals. The pathogenesis of SD does not appear to be limited to specific pathomechanisms and therefore not to specific substances. The differing report distributions by sex and the impact of polypharmacy on the symptoms warrant further investigations.</p>","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142965821","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":"Tocilizumab alleviated lipopolysaccharide-induced acute lung injury by improving PI3K/AKT pathway.","authors":"Junting Weng, Shuoyun Weng, Jitao Xu, Danjuan Liu, Rongjie Guo, Bingbing Shi, Min Chen","doi":"10.1007/s00210-025-03786-9","DOIUrl":"https://doi.org/10.1007/s00210-025-03786-9","url":null,"abstract":"<p><p>Acute lung injury (ALI) is a severe inflammatory condition of the respiratory system, associated with high morbidity and mortality. This study investigates the therapeutic potential of tocilizumab (TZ), an IL-6 receptor inhibitor, in mitigating lipopolysaccharide (LPS)-induced ALI by modulating the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) pathway. An ALI model was established using LPS induction. Lung damage was assessed by hematoxylin-eosin (H&E) staining, alongside measurements of respiratory function, including PaO₂/Fio₂ ratios, lung edema, airway resistance, and lung compliance. Western blotting analyzed the expression of phosphorylated PI3K and AKT (P-PI3K, P-AKT), while ELISA quantified levels of TNF-α, IL-1β, IL-6, and oxidative stress markers. Apoptosis was evaluated using the TUNEL assay, and key apoptotic proteins (Bcl-2, Bax, and caspase-3) were measured by Western blotting. The Cell Counting Kit-8 (CCK-8) assay was employed to determine cell viability. The LPS-induced model exhibited decreased P-PI3K and P-AKT levels, while TZ treatment significantly elevated these markers. TZ also reduced lung tissue damage, improved respiratory function, and decreased inflammation, oxidative stress, and apoptosis. However, co-administration with LY294002 (a PI3K inhibitor) blocked these benefits, reversing the protective effects of TZ. TZ alleviates lung injury and improves outcomes in LPS-induced ALI by enhancing the PI3K/AKT pathway.</p>","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142965875","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 clinical impact of chronopharmacology on current medicine.","authors":"Mert Kaşkal, Mustafa Sevim, Gökay Ülker, Caner Keleş, Berna Terzioğlu Bebitoğlu","doi":"10.1007/s00210-025-03788-7","DOIUrl":"https://doi.org/10.1007/s00210-025-03788-7","url":null,"abstract":"<p><p>One of the goals of clinical pharmacology is to optimize patient treatment by adopting new treatment strategies which will increase the efficacy of the treatment and decrease the adverse effects of the drugs. In the literature, it has shown that the effectiveness and toxicity of medications can vary significantly based on when they are administered, making timing a crucial factor in treatment plans. Chronopharmacology a relatively new branch of clinical pharmacology focuses on adjusting drug administration times to enhance patient outcomes. Chronopharmacology is largely influenced by an individual's circadian rhythm which refers to periodic changes in biological processes depending on the time of the day. The chronopharmacology influences clinical practice, and the accumulating knowledge in this field will likely lead healthcare providers to adopt new strategies for drug treatment regimens. This review aims to summarize the impact of chronopharmacology particularly on current clinical practices and highlight the latest findings related to chronophysiological mechanisms.</p>","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142951989","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":"Comparative effects of dexpanthenol and thymoquinone on colistin-induced neurotoxicity in rats.","authors":"Bulent Durdu, Yasemin Durdu, Eray Metin Guler, Abdurrahim Kocyigit, Gulay Okay","doi":"10.1007/s00210-024-03772-7","DOIUrl":"https://doi.org/10.1007/s00210-024-03772-7","url":null,"abstract":"<p><p>Colistin is used as a last-line treatment for multidrug-resistant gram-negative bacilli. Neurotoxicity limits clinic use of colistin. The use of colistin causes oxidative stress and inflammation. The antioxidant activities of dexpanthenol and thymoquinone are well known. The aim of this research was to investigate and compare the efficacy of dexpanthenol and thymoquinone in alleviating neurotoxicity in rats exposed to colistin therapy. The present study investigated inflammation biomarkers using enzyme-linked immunosorbent assay kits, whereas oxidative stress biomarkers were assessed using several photometric techniques. Serum and brain tissue samples were collected from rats with colistin neurotoxicity following treatment with dexpanthenol and thymoquinone. The administration of dexpanthenol markedly ameliorated colistin-induced oxidative stress indicators (except serum disulfide levels) and inflammatory biomarkers in rats. The effectiveness of thymoquinone exhibited a somewhat restricted scope. Thymoquinone demonstrated a notable enhancement in oxidative stress and inflammatory indicators in rats treated with colistin, except for serum disulfide levels, total antioxidant status (TAS), and brain tissue interleukin 6 (IL-6) levels, as these variables remained unaffected. The administration of dexpanthenol and thymoquinone has demonstrated notable neuroprotective effects in mitigating colistin-induced neurotoxicity in a rat model. A comparison of the neuroprotective properties of dexpanthenol and thymoquinone revealed that dexpanthenol had superior ameliorative effects on serum TAS and brain IL-6 levels compared to thymoquinone. The results of this study indicate that dexpanthenol may exhibit superior efficacy compared to thymoquinone in mitigating the neurotoxic adverse effects associated with colistin.</p>","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142951942","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":"Humic acid from vermicompost effectively regulates the redox status and mitigates the progression of experimental periodontitis.","authors":"Hugo Giordano Tavares, Patrícia Ribeiro Orlando, Ramona Ramalho de Souza Pereira, Caíque Olegário Diniz E Magalhães, Gabriela Silva, Alice Dos Santos Nunes Ferreira, Bruna Caroline Chaves Garcia, Karen Rodrigues Lima, Etel Rocha Vieira, Leonardo Barros Dobbss, Marco Fabrício Dias-Peixoto, Alan Rodrigues Teixeira Machado, Luciano José Pereira, Eric Francelino Andrade","doi":"10.1007/s00210-024-03747-8","DOIUrl":"https://doi.org/10.1007/s00210-024-03747-8","url":null,"abstract":"<p><p>The progression of periodontal disease (PD) involves the action of oxidative stress mediators. Antioxidant agents may potentially attenuate the development of this condition. Thus, we aimed to evaluate the effects of different doses of humic acid (HA), extracted from biomass vermicomposting, on redox status and parameters related to PD progression in rats. Fifty-four adult male Wistar rats were distributed into six experimental groups (control; PD; PD + 40 mg/kg of HA; PD + 80 mg/kg of HA; PD + 160 mg/kg of HA; PD + 320 mg/kg of HA). HA was administered by gavage for 28 days, and PD was induced by ligature on the mandibular first molars on the 14th day of treatment. After euthanasia, alveolar bone loss, oxidative stress in the gum and erythrocytes, serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and creatinine were analyzed. Animals treated with HA showed less bone loss at the dose of 80 mg/kg compared to the untreated PD group (p < 0.05). Animals treated with HA at doses higher than 80 mg/kg showed improvements in local and systemic redox status parameters (total antioxidant activity, thiobarbituric reactive substances, carbonyl derivatives, and superoxide dismutase) compared to the PD group (p < 0.05). Treatment with HA reduced serum levels of creatinine (at doses of 80 and 160 mg/kg) and AST (at doses of 40 and 80 mg/kg) compared to the PD group (p < 0.05). HA treatment attenuated alveolar bone loss and improved local and systemic oxidative stress parameters in ligature-induced PD rats.</p>","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142951934","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":"Coptisine inhibits esophageal carcinoma growth by modulating pyroptosis via inhibition of HGF/c-Met signaling.","authors":"Chunmei Qian, Xing Zhang, Yu-Shi Tian, Lin Yuan, Qiao Wei, Yifu Yang, Midie Xu, Xiaoyu Wang, Menghong Sun","doi":"10.1007/s00210-024-03765-6","DOIUrl":"https://doi.org/10.1007/s00210-024-03765-6","url":null,"abstract":"<p><p>Esophageal carcinoma is a highly prevalent malignancy worldwide. The present study aimed to investigate the mechanism by which the natural compound coptisine affects pyroptosis in esophageal squamous cell carcinoma (ESCC). The expression of c-Met in ESCC patients was assessed by immunohistochemical analysis of tissue microarrays. Natural drugs that bind to c-Met were identified by screening and molecular docking. The effect of coptisine on the proliferation of ESCC cells was detected by CCK-8 and colony formation assays. Cell cycle progression and cell apoptosis were detected by flow cytometry. The levels of mRNAs related to pyroptosis and miR-21 after coptisine treatment were assessed via real-time quantitative PCR. The effect of pyroptosis was evaluated by reactive oxygen species level detection and transmission electron microscopy (TEM) analysis. The expression of proteins related to pyroptosis and the HGF/c-Met pathway was detected by western blotting. A xenograft tumor model was established, and the inhibitory effect of coptisine was evaluated by observing tumor growth. The results showed that the highly expressed protein c-Met in esophageal cancer could bind with coptisine. Coptisine inhibited c-Met phosphorylation and proliferation in ESCC cells. Furthermore, coptisine inhibited the expression of downstream proteins of the HGF/c-Met signaling pathway and induced ROS generation. Tumor xenograft experiments demonstrated that coptisine effectively inhibited tumor growth by reducing the levels of pyroptosis-associated proteins. In conclusion, these findings indicate that inhibition of the HGF/c-Met signaling pathway suppresses pyroptosis to enhance the antitumor effect of coptisine in ESCC and support the potential use of coptisine for EC treatment.</p>","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142951946","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}