Frontiers in Pharmacology最新文献

{"title":"Impact of plant-derived antioxidants on heart aging: a mechanistic outlook.","authors":"Muneer Ahmed Khoso, Heng Liu, Tong Zhao, Wenjie Zhao, Qiang Huang, Zeqi Sun, Khuzin Dinislam, Chen Chen, Lingyi Kong, Yong Zhang, Xin Liu","doi":"10.3389/fphar.2025.1524584","DOIUrl":"10.3389/fphar.2025.1524584","url":null,"abstract":"<p><p>Heart aging involves a complex interplay of genetic and environmental influences, leading to a gradual deterioration of cardiovascular integrity and function. Age-related physiological changes, including ventricular hypertrophy, diastolic dysfunction, myocardial fibrosis, increased arterial stiffness, and endothelial dysfunction, are influenced by key mechanisms like autophagy, inflammation, and oxidative stress. This review aims to explore the therapeutic potential of plant-derived bioactive antioxidants in mitigating heart aging. These compounds, often rich in polyphenols, flavonoids, and other phytochemicals, exhibit notable antioxidant, anti-inflammatory, and cardioprotective properties. These substances have intricate cardioprotective properties, including the ability to scavenge ROS, enhance endogenous antioxidant defenses, regulate signaling pathways, and impede fibrosis and inflammation-promoting processes. By focusing on key molecular mechanisms linked to cardiac aging, antioxidants produced from plants provide significant promise to reduce age-related cardiovascular decline and improve general heart health. Through a comprehensive analysis of preclinical and clinical studies, this work highlights the mechanisms associated with heart aging and the promising effects of plant-derived antioxidants. The findings may helpful for researchers in identifying specific molecules with therapeutic and preventive potential for aging heart.</p>","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":"16 ","pages":"1524584"},"PeriodicalIF":4.4,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11969199/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143795187","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"When <i>HERG</i>-caused LQT2 encounters antisense oligonucleotide: is exon 6 skipping therapy plausible?","authors":"Zequn Zheng, Yongfei Song","doi":"10.3389/fphar.2025.1535259","DOIUrl":"10.3389/fphar.2025.1535259","url":null,"abstract":"<p><p>The unique in-frame exon 6 of the HERG gene as a potential target for antisense oligonucleotide-mediated exon skipping therapy.</p>","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":"16 ","pages":"1535259"},"PeriodicalIF":4.4,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11969117/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143795192","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Histidine-rich glycoprotein inhibits TNF-α-induced tube formation in human vascular endothelial cells.","authors":"Omer Faruk Hatipoglu, Takashi Nishinaka, Kursat Oguz Yaykasli, Shuji Mori, Masahiro Watanabe, Takao Toyomura, Masahiro Nishibori, Satoshi Hirohata, Hidenori Wake, Hideo Takahashi","doi":"10.3389/fphar.2025.1561628","DOIUrl":"10.3389/fphar.2025.1561628","url":null,"abstract":"<p><strong>Introduction: </strong>Tumor necrosis factor-α (TNF-α)-induced angiogenesis plays a critical role in tumor progression and metastasis, making it an important therapeutic target in cancer treatment. Suppressing angiogenesis can effectively limit tumor growth and metastasis. However, despite advancements in understanding angiogenic pathways, effective strategies to inhibit TNF-α-mediated angiogenesis remain limited.</p><p><strong>Methods: </strong>This study investigates the antiangiogenic effects of histidine-rich glycoprotein (HRG), a multifunctional plasma protein with potent antiangiogenic properties, on TNF-α-stimulated human endothelial cells (EA.hy926). Tube formation assays were performed to assess angiogenesis, and gene/protein expression analyses were conducted to evaluate HRG's effects on integrins αV and β8. The role of nuclear factor erythroid 2-related factor 2 (NRF2) in HRG-mediated antiangiogenic activity was also examined through nuclear translocation assays and NRF2 activation studies.</p><p><strong>Results: </strong>At physiological concentrations, HRG effectively suppressed TNF-α-induced tube formation in vitro and downregulated TNF-α-induced expression of integrins αV and β8 at both the mRNA and protein levels. HRG treatment promoted NRF2 nuclear translocation in a time-dependent manner. Furthermore, activation of NRF2 significantly reduced TNF-α-induced tube formation and integrin expression, suggesting that NRF2 plays a key role in HRG-mediated antiangiogenic effects.</p><p><strong>Discussion and conclusion: </strong>Our findings indicate that HRG suppresses TNF-α-induced angiogenesis by promoting NRF2 nuclear translocation and transcriptional activation, which in turn inhibits integrin αV and β8 expression. Given the essential role of angiogenesis in tumor progression, HRG's ability to regulate this process presents a promising therapeutic strategy for cancer treatment.</p>","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":"16 ","pages":"1561628"},"PeriodicalIF":4.4,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11969118/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143795185","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Application of high-dose tranexamic acid in the perioperative period: a narrative review.","authors":"Yushan Duan, Xiaohong Wan, Yiming Ma, Weihua Zhu, Yue Yin, Qingqing Huang, Yuan Yang","doi":"10.3389/fphar.2025.1552511","DOIUrl":"10.3389/fphar.2025.1552511","url":null,"abstract":"<p><strong>Objective: </strong>To investigate the efficacy and safety of high-dose tranexamic acid in different types of surgeries and provide a reference for clinical practice.</p><p><strong>Methods: </strong>We systematically searched PubMed, Cochrane Library, Science, Embase, and CNKI databases, from their inception to January 2025, to include representative literature related to high-dose tranexamic acid in the perioperative period for a thematic synthesis. The analysis focused on clinical evidence related to obstetric, cardiac, urologic, orthopedic, and spinal surgeries.</p><p><strong>Results: </strong>High-dose tranexamic acid markedly reduces blood loss and transfusion requirements in most types of surgery; however, the optimal dose varies by surgery type. Available studies have shown a favorable safety profile; however, some areas (e.g., cardiac surgery) still require careful monitoring for seizures and risk of thrombotic events.</p><p><strong>Conclusion: </strong>The clinical benefit of high-dose tranexamic acid should be assessed based on surgical characteristics and patient individualization. More multicenter studies are needed to clarify the dose-effect relationship and long-term safety.</p>","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":"16 ","pages":"1552511"},"PeriodicalIF":4.4,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11968675/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143794703","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Recent insights on the impact of SWELL1 on metabolic syndromes.","authors":"Mianhong Qin, Xuejie Yi, Ziqiang Duan, Bo Chang, Tao Li","doi":"10.3389/fphar.2025.1552176","DOIUrl":"10.3389/fphar.2025.1552176","url":null,"abstract":"<p><p>SWELL1 is a key component of the volume-regulated anion channel (VRAC) and participates in cell volume regulation as an ion channel plasma membrane protein. While early studies focused on its role in immune cell development and tumor progression, recent studies have revealed that SWELL1 plays an important role in metabolic diseases. Studies have shown that SWELL1 is extensively involved in physiological processes in peripheral metabolic tissues, including adipocyte hypertrophy, skeletal muscle volume regulation, insulin secretion, and hepatic lipid metabolism through interactions with the insulin signaling pathway. These functions play key roles in the pathogenesis of obesity, type 2 diabetes mellitus (T2DM), and non-alcoholic fatty liver disease (NAFLD), suggesting that SWELL1 may be a new target for the treatment of metabolic diseases. In this review, we focus on the structural and functional characteristics of SWELL1 to provide an in-depth explanation of its role in the development of metabolic syndrome, especially the regulation of the insulin signaling pathway, and provide a basis for the development of therapeutic strategies for metabolic diseases targeting SWELL1.</p>","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":"16 ","pages":"1552176"},"PeriodicalIF":4.4,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11968765/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143795189","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Necessity for Polypharmacological Research - An Editorial on 'Network Polypharmacology of ATP-binding Cassette (ABC) and Solute Carrier (SLC) Transporters'.","authors":"Muhammad Rafehi, Kapil Juvale, Lukasz Pulaski, Sven Marcel Stefan","doi":"10.3389/fphar.2025.1561247","DOIUrl":"https://doi.org/10.3389/fphar.2025.1561247","url":null,"abstract":"","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":"16 ","pages":"1561247"},"PeriodicalIF":4.4,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11976318/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143811035","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Circulating tumor DNA: a revolutionary approach for early detection and personalized treatment of bladder cancer.","authors":"Yan Zhou, Rongzhong Wang, Mingtang Zeng, Sijia Liu","doi":"10.3389/fphar.2025.1551219","DOIUrl":"10.3389/fphar.2025.1551219","url":null,"abstract":"<p><p>Bladder cancer is a malignant tumor with a high global incidence and recurrence rate. Traditional diagnostic methods, such as cystoscopy and urine cytology, have limitations in sensitivity and specificity, particularly in detecting low-grade bladder cancer. Circulating tumor DNA (ctDNA) offers a non-invasive alternative, reflecting tumor genetic characteristics through blood samples. It demonstrates high sensitivity and repeatability, making it a promising tool for early detection, recurrence monitoring, and treatment evaluation. Clinical studies have shown that ctDNA not only detects tumor burden but also captures dynamic tumor mutations, aiding in personalized treatment strategies. Despite its potential, clinical implementation of ctDNA faces challenges, including optimization of detection techniques, standardization, and the cost of testing. This paper explores the role of ctDNA in advancing bladder cancer diagnosis and treatment, with a focus on refining its clinical application and guiding future research toward improved patient outcomes.</p>","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":"16 ","pages":"1551219"},"PeriodicalIF":4.4,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11968738/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143794886","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical efficacy and pharmacological mechanism of Er Zhi Tian Gui formula in enhancing IVF-ET outcomes for diminished ovarian reserve.","authors":"Wen Chen, Fang Lian, Jingyan Song, Chen Yu, Shengyong Ding, Haicui Wu","doi":"10.3389/fphar.2025.1552581","DOIUrl":"10.3389/fphar.2025.1552581","url":null,"abstract":"<p><strong>Objective: </strong>To investigate the efficacy of the Er Zhi Tian Gui Formula (EZTGF) in diminished ovarian reserve (DOR) patients undergoing <i>in vitro</i> fertilization-embryo transfer (IVF-ET); to examine the pharmacological mechanism of EZTGF in inhibiting ovarian granulosa cell (OGC) apoptosis.</p><p><strong>Methods: </strong>A total of 120 DOR patients undergoing IVF-ET in the Affiliated Hospital of Shandong University of TCM from March to December 2021 were randomly assigned to the EZTGF (n = 60) or Placebo (n = 60) groups. All participants followed a gonadotropin-releasing hormone antagonist protocol for controlled ovarian stimulation, with interventions starting on days 2-3 of the preceding menstrual cycle and continuing until the trigger day. IVF-ET outcomes measured included the number of oocytes retrieved, embryo quality, and pregnancy rates. NEAT1, miR-10b-3p, and FOXO3a OGCs expression was analyzed via qRT-PCR. Mechanistic studies were conducted using KGN cells, with dual-luciferase reporter assays confirming regulatory relationship between NEAT1, miR-10b-3p, and FOXO3a.</p><p><strong>Results: </strong>A total of 116 patients completed the trial (58 in each group). The EZTGF group showed a significant increase in both the number (especially at the cleavage stage) and rate of high-quality embryos, compared with the Placebo group (P < 0.05). No statistically significant differences in pregnancy outcomes were observed (P > 0.05). Cellular experiments showed that miR-10b-3p inhibits proliferation and promotes apoptosis in oocyte granulosa cells (OGCs). Dual luciferase reporter gene assay confirms target-regulatory relationship of NEAT1 with miR-10b-3p, miR-10b-3p and FOXO3a. EZTGF treatment partially reversed the low expression of NEAT1 and FOXO3a, and the high expression of miR-10b-3p in OGCs from DOR patients.</p><p><strong>Conclusion: </strong>Treatment with EZTGF enhances embryo quality in women with DOR undergoing IVF-ET, which can be partially attributed to modulation of the NEAT1/miR-10b-3p/FOXO3a pathway. Trial registration: ChiCTR2100052522.</p>","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":"16 ","pages":"1552581"},"PeriodicalIF":4.4,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11969198/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143794893","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Recent advancement in prevention against hepatotoxicity, molecular mechanisms, and bioavailability of gallic acid, a natural phenolic compound: challenges and perspectives.","authors":"Peng Chen, Fanzhao Zou, Wei Liu","doi":"10.3389/fphar.2025.1549526","DOIUrl":"10.3389/fphar.2025.1549526","url":null,"abstract":"<p><p>Drug-induced liver injury (DILI) results from the liver toxicity caused by drugs or their metabolites. Gallic acid (GA) is a naturally occurring secondary metabolite found in many fruits, plants, and nuts. Recently, GA has drawn increasing attention due to its potent pharmacological properties, particularly its anti-inflammatory and antioxidant capabilities. To the best of our knowledge, this is the first review to focus on the pharmacological properties of GA and related molecular activation mechanisms regarding protection against hepatotoxicity. We also provide a thorough explanation of the physicochemical properties, fruit sources, toxicity, and pharmacokinetics of GA after reviewing a substantial number of studies. Pharmacokinetic studies have shown that GA is quickly absorbed and eliminated when taken orally, which restricts its use in development. However, the bioavailability of GA can be increased by optimizing its structure or changing its form of administration. Notably, according to toxicology studies conducted on a range of animals and clinical trials, GA rarely exhibits toxicity or side effects. The antioxidation mechanisms mainly involved Nrf2, while anti-inflammatory mechanisms involved MAPKs and NF-κB signaling pathways. Owing to its marked pharmacological properties, GA is a prospective candidate for the management of diverse xenobiotic-induced hepatotoxicity. We also discuss the applications of cutting-edge technologies (nano-delivery systems, network pharmacology, and liver organoids) in DILI. In addition to guiding future research and development of GA as a medicine, this study offers a theoretical foundation for its clinical application.</p>","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":"16 ","pages":"1549526"},"PeriodicalIF":4.4,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11968354/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143795188","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The effect of high-fat diet on the pharmacokinetics of ondansetron hydrochloride tablets in healthy Chinese subjects.","authors":"Na Zhao, Caiyun Jia, Yiting Hu, Xue Sun, Haojing Song, Bo Qiu, Wanjun Bai, Zhanjun Dong","doi":"10.3389/fphar.2025.1512857","DOIUrl":"10.3389/fphar.2025.1512857","url":null,"abstract":"<p><strong>Background: </strong>This study aimed to assess how a high-fat diet impacts the pharmacokinetics and safety characteristics of 8 mg Ondansetron hydrochloride tablets among healthy Chinese individuals.</p><p><strong>Subjects and methods: </strong>The findings presented here were obtained from a bioequivalence study, in which individuals were randomly assigned to consume Ondansetron hydrochloride tablets either following a meal or subsequent to a high-fat diet containing 978.6 kcal, with 54.6% of the calories derived from fat. The plasma concentrations of Ondansetron were measured through the utilization of high-performance liquid chromatography-mass spectrometry (LC-MS/MS) after collecting blood samples. For the computation of pharmacokinetic parameters, the non-compartmental module from Phoenix WinNonlin Version 8.2 was utilized Additionally, the BE module within WinNonLin was utilized to statistically analyze key pharmacokinetic metrics, including the maximum level of concentration (Cmax), the area beneath the concentration-time curve spanning from zero to the final quantifiable time point (AUC_0-t), and the area beneath the concentration-time curve extending from zero to a theoretical limitless point (AUC_0-∞) in plasma. A total of 53 healthy subjects participated in the study and were divided into a fasted cohort and a postprandial cohort.</p><p><strong>Results: </strong>Ondansetron had lower Cmax, AUC_0-t, and AUC_0-∞in plasma when taken with food compared to when taken on an empty stomach, with the 90% confidence interval falling outside the acceptable range of 80.00%-125.00%.The occurrence of treatment-related side effects was comparable in both the fasted and postprandial groups, as was the incidence of adverse drug reactions.</p><p><strong>Conclusion: </strong>The study concluded that the high-fat meal had a notable impact on how Ondansetron is processed in the body. Healthy subjects tolerated all treatments well and safely under both postprandial and fasted conditions.</p><p><strong>Clinical trial registration: </strong>http://www.chinadrugtrials.org.cn/index.html, identifier CTR20213116.</p>","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":"16 ","pages":"1512857"},"PeriodicalIF":4.4,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11968426/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143795191","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}