Naunyn-Schmiedeberg's archives of pharmacology最新文献

{"title":"Comprehensive insights into pancreatic cancer treatment approaches and cutting-edge nanocarrier solutions: from pathology to nanomedicine.","authors":"Rohit Sharma, Sourabh Kumar, Kumari Komal, Rashmi Ghosh, Shubham Thakur, Ravi Raj Pal, Manish Kumar","doi":"10.1007/s00210-025-04094-y","DOIUrl":"https://doi.org/10.1007/s00210-025-04094-y","url":null,"abstract":"<p><p>Pancreatic cancer is one of the most lethal malignancies worldwide. It is characterized by poor prognosis, high mortality, and recurrence rates. Various modifiable and non-modifiable risk factors are associated with pancreatic cancer incidence. Available treatments for pancreatic cancer include surgery, chemotherapy, radiotherapy, photodynamic therapy, supportive care, targeted therapy, and immunotherapy. However, the survival rates for PC are very low. Regrettably, despite efforts to enhance prognosis, the survival rate of pancreatic cancer remains relatively low. Therefore, it is essential to investigate new approaches to improve pancreatic cancer treatment. By synthesizing current knowledge and identifying existing gaps, this article provides a comprehensive overview of risk factors, pathology, conventional treatments, targeted therapies, and recent advancements in nanocarriers for its treatment, along with various clinical trials and patents that justify the safety and efficacy of innovative carriers for drug delivery systems. Ultimately, this review underscores the potential of these innovative formulations to improve outcomes and contribute significantly to the advancement of Pancreatic Cancer treatment. Together, these insights highlight nano-formulations as a promising frontier for effectively treating Pancreatic Cancer.</p>","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143811682","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":"Targeting diabetes with flavonoids from Indonesian medicinal plants: a review on mechanisms and drug discovery.","authors":"Tubagus Rayyan Fitra Sinuhaji, Sintha Ramadhani, Volta Kellik Setiawan, Umi Baroroh","doi":"10.1007/s00210-025-04139-2","DOIUrl":"https://doi.org/10.1007/s00210-025-04139-2","url":null,"abstract":"<p><p>The rich biodiversity of Indonesia provides a wide variety of plants rich in flavonoids, which show promising potential as antidiabetic agents. Flavonoids are polyphenolic compounds recognized for their broad biological activities, such as antioxidant, anti-inflammatory, and antidiabetic effects. Traditional Indonesian medicinal plants such as Syzygium cumini, Moringa oleifera, and Curcuma longa are currently being studied for their flavonoid content and potential in diabetes treatment. Studies suggest that flavonoids can influence crucial pathways in diabetes management, including enhancing insulin sensitivity, boosting insulin production, and safeguarding pancreatic β cells against damage caused by oxidative stress. For example, quercetin and kaempferol, flavonoids in many Indonesian plants, have demonstrated potential for managing glucose metabolism and lowering high blood sugar levels. Additionally, these substances have been shown to inhibit enzymes such as α-glucosidase and α-amylase, which are involved in the breakdown of carbohydrates, thus aiding in the regulation of blood sugar levels after meals. The antioxidant qualities of flavonoids play a crucial role in fighting oxidative stress and are a significant contributor to the development of diabetes and related complications. Flavonoids help neutralize free radicals and enhance the body's antioxidant protection, reducing oxidative harm and promoting metabolic wellness. Additionally, their anti-inflammatory properties aid in reducing the chronic inflammation linked to insulin resistance and β-cell dysfunction. Formulation advancements, such as nanocarrier technology, have been explored to boost the effectiveness of flavonoid-based therapies. Due to its vast plant diversity, Indonesia offers a potential reservoir for new antidiabetic drugs, meriting additional research and development with the aim of this review providing new knowledge on the potential of flavonoids that can play a role in the treatment of diabetes.</p>","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143811786","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 current findings on the gut-liver axis and the molecular basis of NAFLD/NASH associated with gut microbiome dysbiosis.","authors":"Seema Sharma, Nishant Tiwari, Sampat Singh Tanwar","doi":"10.1007/s00210-025-04069-z","DOIUrl":"https://doi.org/10.1007/s00210-025-04069-z","url":null,"abstract":"&lt;p&gt;&lt;p&gt;Recent research has highlighted the complex relationship between gut microbiota, metabolic pathways, and nonalcoholic fatty liver disease (NAFLD) progression. Gut dysbiosis, commonly observed in NAFLD patients, impairs intestinal permeability, leading to the translocation of bacterial products like lipopolysaccharides, short-chain fatty acids, and ethanol to the liver. These microbiome-associated mechanisms contribute to intestinal and hepatic inflammation, potentially advancing NAFLD to NASH. Dietary habits, particularly those rich in saturated fats and fructose, can modify the microbiome composition, leading to dysbiosis and fatty liver development. Metabolomic approaches have identified unique profiles in NASH patients, with specific metabolites like ethanol linked to disease progression. While bariatric surgery has shown promise in preventing NAFLD progression, the role of gut microbiome and metabolites in this improvement remains to be proven. Understanding these microbiome-related pathways may provide new diagnostic and therapeutic targets for NAFLD and NASH. A comprehensive review of current literature was conducted using multiple medical research databases, including PubMed, Scopus, Web of Science, Embase, Cochrane Library, ClinicalTrials.gov, ScienceDirect, Medline, ProQuest, and Google Scholar. The review focused on studies that examine the relationship between gut microbiota composition, metabolic pathways, and NAFLD progression. Key areas of interest included microbial dysbiosis, endotoxin production, and the influence of diet on gut microbiota. The analysis revealed that gut dysbiosis contributes to NAFLD through several mechanisms, diet significantly influences gut microbiota composition, which in turn affects liver function through the gut-liver axis. High-fat diets can lead to dysbiosis, altering microbial metabolic activities and promoting liver inflammation. Specifically, gut microbiota-mediated generation of saturated fatty acids, such as palmitic acid, can activate liver macrophages and increase TNF-α expression, contributing to NASH development. Different dietary components, including cholesterol, fiber, fat, and carbohydrates, can modulate the gut microbiome and influence NAFLD progression. This gut-liver axis plays a crucial role in maintaining immune homeostasis, with the liver responding to gut-derived bacteria by activating innate and adaptive immune responses. Microbial metabolites, such as bile acids, tryptophan catabolites, and branched-chain amino acids, regulate adipose tissue and intestinal homeostasis, contributing to NASH pathogenesis. Additionally, the microbiome of NASH patients shows an elevated capacity for alcohol production, suggesting similarities between alcoholic steatohepatitis and NASH. These findings indicate that targeting the gut microbiota may be a promising approach for NASH treatment and prevention. Recent research highlights the potential of targeting gut microbiota for managing nonalcohol","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143811791","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":"Comprehensive review of leonurine: harnessing its therapeutic potential for chronic diseases.","authors":"Mukesh Kumar Manickasamy, Uzini Devi Daimary, Anjana Sajeev, Mohamed Abbas, Mohammed S Alqahtani, Ayman Abdulhammed, Ajaikumar B Kunnumakkara","doi":"10.1007/s00210-025-04087-x","DOIUrl":"https://doi.org/10.1007/s00210-025-04087-x","url":null,"abstract":"<p><p>Chronic diseases (CD) pose a significant global health challenge, affecting millions of individuals and contributing to substantial morbidity, mortality, and healthcare burden. Therapeutic approaches primarily aim at symptom management through pharmacotherapy, lifestyle modifications, dietary interventions, and regular physical activity. Given the persistent challenge of limited treatment options, scientific research has increasingly focused on exploring natural compounds for their therapeutic potential. Leonurine, a natural compound first isolated from the plant Herba leonuri in 1930, has garnered significant attention due to its extensive pharmacological properties relevant to the treatment of CDs. Extensive studies over the past have revealed that leonurine exhibits anticancer, antidiabetic, anti-inflammatory, and antioxidant activities. These effects are mediated through the modulation of various signaling pathways, including the TGF-β/Smad2, Nrf-2, JNK, NF-κB, BDNF/TrkB/CREB, TLR4/NF-κB/TNF-α, ATF4/CHOP/ASCL4, Akt, HIF-1, SHH/GLI, and mTOR/ERK, whose dysregulation is implicated in the pathogenesis of various CDs. Furthermore, leonurine regulates the levels of multiple pro-inflammatory cytokines, including numerous interleukins and TNF-α, indicating its potential in treating a wide range of chronic conditions, including cardiovascular, neurological, skeletal, and renal diseases. This review seeks to present an in-depth analysis of leonurine's therapeutic potential, emphasizing its promise in the management of various CDs. It also outlines potential avenues for future research to fully harness its pharmacological advantages in treating these conditions.</p>","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143811778","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":"Regulation of immune-mediated chemoresistance in cancer by lncRNAs: an in-depth review of signaling pathways.","authors":"Saade Abdalkareem Jasim, Farag M A Altalbawy, Subasini Uthirapathy, Ashok Kumar Bishoyi, Suhas Ballal, Abhayveer Singh, Anita Devi, Alexey Yumashev, Yasser Fakri Mustafa, Munther Kadhim Abosaoda","doi":"10.1007/s00210-025-04081-3","DOIUrl":"https://doi.org/10.1007/s00210-025-04081-3","url":null,"abstract":"<p><p>Resistance to cancer therapies is increasingly recognized as being influenced by long non-coding RNAs (lncRNAs), which are pivotal in regulating cellular functions and gene expression. Elucidating the intricate relationship between lncRNAs and the mechanisms underlying drug resistance is critical for advancing effective therapeutic strategies. This study offers an in-depth review of the regulatory roles lncRNAs play in various signaling and immunological pathways implicated in cancer chemoresistance. lncRNA-mediated influence on drug resistance-related signaling pathways will be presented, including immune evasion mechanisms and other essential signaling cascades. Furthermore, the interplay between lncRNAs and the immune landscape will be dissected, illustrating their substantial impact on the development of chemoresistance. Overall, the potential of lncRNA-mediated signaling networks as a therapeutic strategy to combat cancer resistance has been highlighted. This review reiterates the fundamental role of lncRNAs in chemoresistance and proposes promising avenues for future research and the development of targeted therapeutic interventions.</p>","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143811783","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":"Outpatient utilization trend of bronchodilator and anti-inflammatory agents in the pandemic and beyond.","authors":"N Ipek Kirmizi Sonmez, Onur Gultekin, Ahmet Akici, Yelda Basbug, Volkan Aydin","doi":"10.1007/s00210-025-04099-7","DOIUrl":"https://doi.org/10.1007/s00210-025-04099-7","url":null,"abstract":"<p><p>As COVID-19 primarily affects the respiratory system, it may have impacted utilization patterns of drugs used in obstructive airway diseases (DOADs). We examined nationwide DOAD utilization trends before, during, and after pandemic measures. We collected data on DOADs (ATC-Code: R03) between 01.01.2017-28.02.2023 from IQVIA-Turkey. National outpatient sales and prescription projections were converted into consumption data, expressed as defined daily dose per 1,000 inhabitants (DID). We compared mean monthly consumption, costs, and quarterly DOADs use across \"before restrictions\" (BfR), \"during restrictions\" (DuR), and \"after restrictions\" (AfR) periods. We identified 433.5 million DOAD units consumed, costing €3.3 billion; inhaled-DOADs accounted for 73.1%. Mean monthly DOAD consumption remained stable (BfR: 67.8 ± 3.1 DID; DuR: 74.2 ± 12.5 DID; AfR: 74.2 ± 14.6 DID; p > 0.05). Inhaled-DOADs exhibited a similar pattern, except the anticholinergics with a significant increase in the DuR (19.4 ± 3.3 DID) compared to the BfR (16.1 ± 2.3 DID, p < 0.001). Also inhaled-corticosteroid monotherapy rose significantly between BfR (4.1 ± 0.9 DID) and AfR (5.3 ± 1.3 DID, p < 0.05). Montelukast, constituting 76.6% of systemic-DOADs, had higher consumption in AfR (15.0 ± 2.8 DID) than in BfR (11.7 ± 2.2 DID, p < 0.001) and DuR (12.9 ± 2.4 DID, p < 0.05). Overall DOAD prescriptions declined in DuR and trended upward in AfR but didn't reach pre-pandemic levels, except for new users of montelukast and long-acting beta agonists. Our study showed increased use of inhaled anticholinergics, glucocorticoid monotherapy, and montelukast within a generally stable overall DOAD utilization. This may reflect varied responses to bronchodilation and anti-inflammatory treatment needs during the pandemic and beyond.</p>","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143811782","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":"Targeting EZH2 in autoimmune diseases: unraveling epigenetic regulation and therapeutic potential.","authors":"Hashem Ahmed Abu Harirah, Mohammed Hashim Mohammed, Sami Ahmed Zaher Basha, Subasini Uthirapathy, Subbulakshmi Ganesan, Aman Shankhyan, Girish Chandra Sharma, Anita Devi, Abed J Kadhim, Naher H S","doi":"10.1007/s00210-025-04127-6","DOIUrl":"https://doi.org/10.1007/s00210-025-04127-6","url":null,"abstract":"<p><p>Approximately 8-10% of the global population is affected by autoimmune diseases (ADs), which encompass a wide array of idiopathic conditions resulting from dysregulated immune responses. The enzymatic component of the polycomb-repressive complex 2 (PRC2), enhancer of zeste homolog 2 (EZH2, also referred to as KMT6), functions as a methyltransferase possessing a SET domain that plays crucial roles in epigenetic regulation, explicitly facilitating the methylation of histone H3 at lysine 27. Notably, EZH2 is catalytically inactive and requires association with EED and SUZ12 to form an active PRC2 complex. Hyperactivation of EZH2 has been implicated in various malignancies, prompting the development of EZH2 inhibitors as therapeutic agents for several cancers, including lymphoma, prostate, breast, and colon cancer. The application of EZH2-targeting therapies has also been explored in the context of autoimmune diseases. While there have been advancements in certain ADs, responses can vary significantly, as evidenced by mixed outcomes in cases such as inflammatory bowel disease. Consequently, the dual role of EZH2 and the therapeutic potential of its inhibitors in the treatment of ADs remain nascent fields of study. This review will elucidate the interplay between EZH2 and autoimmune diseases, highlighting emerging insights and therapeutic avenues.</p>","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143811788","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":"Corrigendum to \"Apoptosis-inducing factor plays a role in the pathogenesis of hepatic and renal injury during cholestasis [Naunyn-Schmiedeberg's Archives of Pharmacology (2021) 394:1191-1203; DOI: https://doi.org/10.1007/s00210 - 020 - 02041 - 7]\".","authors":"Vahid Ghanbarinejad, Akram Jamshidzadeh, Bahman Khalvati, Omid Farshad, Huifeng Li, Xiong Shi, Yuanyu Chen, Mohammad Mehdi Ommati, Reza Heidari","doi":"10.1007/s00210-025-04124-9","DOIUrl":"https://doi.org/10.1007/s00210-025-04124-9","url":null,"abstract":"","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143811780","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":"Harnessing the metastatic potential of human osteosarcoma cells by natural coumarin galbanic acid.","authors":"Abdolreza Ahmadi, Fatemehsadat Hosseini, Zahra Nasiri Sarvi, Mehrdad Iranshahi, Fatemeh B Rassouli","doi":"10.1007/s00210-025-04128-5","DOIUrl":"https://doi.org/10.1007/s00210-025-04128-5","url":null,"abstract":"<p><p>Osteosarcoma (OS), the most common primary malignant bone tumor in children and adolescents, presents a significant challenge due to its high propensity for metastasis. This reality underscores the urgent need for innovative therapies targeting metastatic progression to improve patient outcomes. The present study aimed to investigate the potential of galbanic acid (GBA), a natural sesquiterpene coumarin, on the metastasis of OS cells for the first time. Utilizing bioinformatics tools, shared therapeutic targets between GBA and OS were identified, with key hub genes prioritized through network analysis. Molecular docking and dynamics simulations were performed to assess the binding affinity and stability of GBA with MMP-2, MMP-9, ADAM17, and ADAMTS5. For experimental validation, GBA was isolated from Ferula szowitsiana via thin-layer chromatography, and its effects on MG-63 cells were evaluated through a series of assays: alamarBlue assay and flow cytometry for viability and apoptosis, scratch assay for migration, transwell assay for invasive potential, fibronectin adhesion assay for cell-matrix interaction, and gelatin zymography for MMP activity. Computational analyses revealed MMPs and ADAMs as common targets of GBA and OS. Molecular docking and dynamics simulations indicated strong and stable interactions between GBA with MMP-2, MMP-9, ADAM17, and ADAMTS5. Experimental studies revealed that treatment with 100 μM GBA did not induce significant toxicity in MG-63 cells. However, GBA significantly (p < 0.01) altered cell migration, invasion, and adhesion, which was associated with a marked reduction in the enzymatic activity of MMP-2 and MMP-9. This research highlights the therapeutic potential of GBA in mitigating the metastatic properties of OS cells, suggesting a promising avenue for future treatment strategies.</p>","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143795956","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":"Schmiedeberg Medal for Thomas Wieland: an artist of G-protein signaling.","authors":"Susanne Lutz, Friederike Cuello, Roland Seifert","doi":"10.1007/s00210-025-04101-2","DOIUrl":"https://doi.org/10.1007/s00210-025-04101-2","url":null,"abstract":"","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143795961","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}