Frontiers in Pharmacology最新文献

{"title":"Ethnobotanical survey of medicinal plants in the southern mountain area of Kunyu mountain, China.","authors":"Zicheng Wang, Zhe Li, Zihan Xu, Xingjie Liu, Yinglin Wang, Ye Liu, Minghan Zhang, Huajuan Zhang, Xinyu Li, Jie Zhou, Jia Li, Qian Liu, Lingna Wang, Yongqing Zhang, Shaoping Wang, Ying Lin","doi":"10.3389/fphar.2025.1598940","DOIUrl":"10.3389/fphar.2025.1598940","url":null,"abstract":"<p><strong>Introduction: </strong>The southern mountainous area of Kunyu Mountain is in the Jiaodong Peninsula of China, which is rich in medicinal plant resources. For a long time, the residents in the Southern Mountain area of Kunyu Mountain have used a variety of plants for pharmacy practice and have accumulated rich knowledge of medicinal plants. Although medicinal plants were widely used, there were no reports on the medicinal plants used by residents in the southern mountainous area of Kunyu Mountain. This study aimed to document the medicinal plants and evaluate the associated traditional knowledge possessed by residents of the southern mountainous area of Kunyu Mountain.</p><p><strong>Methods: </strong>Through face-to-face interviews with 256 residents, the species, preparation, and use of medicinal plants, and related traditional medicinal knowledge were quantitatively analyzed using the Informant Consensus Factor (FIC) and the Relative Frequency of Citation (RFC).</p><p><strong>Results: </strong>We identified 338 species of medicinal plants in this study, belonging to 87 families and 230 genera. Among these, Asteraceae was the dominant family and the whole grass was the most commonly used part for drug preparation, and decoction and oral administration were the most common preparation methods and routes of administration, respectively. In terms of utilization rate, <i>Crataegus pinnatifida</i> var. <i>major</i> (0.2), <i>Crataegus pinnatifida</i> (0.2), <i>Platycodon grandiflorus</i> (0.2), <i>Yulania denudata</i> (0.2), and <i>Zanthoxylum bungeanum</i> (0.2) had higher RFC values, and the five plants above were the most important medicinal plants used by the residents in this area. Besides, compared with China Pharmacopoeia, four new therapeutic uses of three known plants were found. Among the 16 disease categories in the International Classification of Primary Care (ICPC-2), Respiratory system diseases (FIC: 0.8), Digestive system diseases (FIC: 0.8), and General and unspecified system diseases (FIC: 0.8) were the most reported.</p><p><strong>Discussion: </strong>This study lists the species of medicinal plants on the southern mountainous area of Kunyu Mountain. It records their therapeutic uses, which could provide a reference for further chemical and pharmacological studies on medicinal plants.</p>","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":"16 ","pages":"1598940"},"PeriodicalIF":4.8,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12486596/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145212270","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":"Efficacy and safety of antibody-drug conjugates for HER2-expressing advanced gastric and gastroesophageal junction adenocarcinoma: a systematic review and meta-analysis.","authors":"Danxue Huang, Feilong Sun, Su Li, Liyuan Ke","doi":"10.3389/fphar.2025.1668511","DOIUrl":"10.3389/fphar.2025.1668511","url":null,"abstract":"<p><strong>Background: </strong>Antibody-drug conjugates (ADCs) represent a promising therapeutic modality for gastric cancer. Given the highly heterogeneous nature of this malignancy, the efficacy and safety profile of ADC treatment warrant comprehensive evaluation.</p><p><strong>Methods: </strong>A systematic search of online databases identified prospective trials published through June 2025. Pooled estimates for OS, PFS, ORR, DCR, and TRAEs were derived using a random-effects model. Subgroup analyses were performed, stratified according to HER2 status, primary tumor location, line of therapy, and use of combination treatment.</p><p><strong>Results: </strong>A total of 1779 patients from 13 prospective trials (18 reports) were included. The pooled ORR was 67% (95% CI: 53%-82%) for first-line ADC therapy, 40% (95% CI: 29%-51%) for second-line regimens, and 27% (95% CI: 16%-38%) for third-line regimens. In second-line or later therapy, HER2-positive patients achieved a superior ORR relative to HER2-low subgroups (39%, 30%-47% vs. 25%, 11%-39%). The overall pooled median OS was 11.95 months (95% CI: 9.93-13.96), with a median PFS of 4.94 months (95% CI: 3.92-5.96). Stratification by line of therapy revealed a median OS of 19.67 months (95% CI: 15.79-23.55) for first-line <i>versus</i> 11.65 months (8.09-15.22) for second-line and 9.37 months (7.38-11.37) for third-line, with corresponding median PFS of 10.57 months (6.37-14.77) vs. 4.13 months (2.43-5.83) and 4.50 months (3.51-5.50) respectively. TRAEs occurred in 98% (95% CI: 96%-100%) of patients (any-grade), with grade 3-5 events in 60% (52%-69%).</p><p><strong>Conclusion: </strong>This meta-analysis establishes ADCs as a promising therapeutic approach for advanced gastric or gastroesophageal junction cancer (GC/GEJC), demonstrating efficacy in both HER2-positive and HER2-low patient populations.</p><p><strong>Systematic review registration: </strong>https://www.crd.york.ac.uk/PROSPERO/view/CRD420251066208, identifier CRD420251066208.</p>","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":"16 ","pages":"1668511"},"PeriodicalIF":4.8,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12484031/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145211998","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":"Correction: The potential of medicinal food plant <i>Panax ginseng</i> C. A. Mey. in managing chronic diseases via gut microbiota regulation: a systematic review of mechanisms and evidence.","authors":"Meng Gao, Haijing Wang, Xiaojing Chen, Wensheng Wang, Yongmei Liu","doi":"10.3389/fphar.2025.1697027","DOIUrl":"https://doi.org/10.3389/fphar.2025.1697027","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.3389/fphar.2025.1650565.].</p>","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":"16 ","pages":"1697027"},"PeriodicalIF":4.8,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12485231/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145212211","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":"Risk factor identification for delayed excretion in pediatric high-dose methotrexate therapy: a machine learning analysis of real-world data.","authors":"Chengyu Zhou, Yali Qian, Yao Xue, Liucheng Rong, Yu Wan, Kaiqiang Leng, Hongjun Miao, Feng Chen, Yongjun Fang, Xuhua Ge","doi":"10.3389/fphar.2025.1662718","DOIUrl":"10.3389/fphar.2025.1662718","url":null,"abstract":"<p><strong>Purpose: </strong>This study was to identify risk factors associated with delayed methotrexate (MTX) excretion in pediatric patients receiving high-dose MTX (HDMTX) therapy based on real-world data, and to develop and evaluate a predictive model.</p><p><strong>Methods: </strong>Clinical data were retrospectively collected from 1,485 pediatric HDMTX chemotherapy cycles at the Children's Hospital affiliated with Nanjing Medical University between 2021 and 2023. Key predictive variables were identified by Least Absolute Shrinkage and Selection Operator (LASSO) regression, Random Forest (RF), and Support Vector Machine Recursive Feature Elimination (SVM-RFE), and then incorporated into predictive models for MTX delayed excretion using Logistic Regression (LR), Naive Bayes (NB), Support Vector Machine (SVM), and Extreme Gradient Boosting (XGBoost). Bootstrap was employed to internally validate these models and identify the best-performing one, and then SHapley Additive exPlanations (SHAP) values were utilized to provide both global and local interpretations.</p><p><strong>Results: </strong>Among the 1,485 pediatric HDMTX chemotherapy cycles, 26.1% were associated with delayed MTX excretion. Serum creatinine (Scr), total drug dose (Dose), alkaline phosphatase (ALP), creatine kinase (CK), blood urea nitrogen (Urea), gamma-glutamyl transferase (GGT), hemoglobin (HB), and height were identified as key predictors of delayed excretion. Internal validation showed that the XGBoost model performed best, with an accuracy of 0.780, an F1 score of 0.669, an area under the Receiver Operating Characteristic curve (AUROC) of 0.842, and a Brier score of 0.136. Decision Curve Analysis (DCA) also demonstrated favorable clinical utility. SHAP analysis revealed that Scr was the most important risk factor for delayed MTX excretion in the XGBoost model. This XGBoost model has been translated into a convenient tool to facilitate its utility in clinical settings.</p><p><strong>Conclusion: </strong>The XGBoost model demonstrated good predictive performance and clinical utility for delayed MTX excretion in pediatric patients.</p>","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":"16 ","pages":"1662718"},"PeriodicalIF":4.8,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12483887/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145212180","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 role of α-hydroxybutyrate in modulating sepsis progression: identification of key targets and biomarkers through multi-database data mining, machine learning, and unsupervised clustering.","authors":"Qing Lu, Yujie Wu, Dayong Liao, Ying Sun","doi":"10.3389/fphar.2025.1615269","DOIUrl":"10.3389/fphar.2025.1615269","url":null,"abstract":"<p><strong>Background: </strong>Sepsis remains a major cause of mortality and morbidity worldwide. Recent studies suggest that gut microbiota-derived metabolites, such as α-hydroxybutyrate (α-HB), may play a critical role in the progression of sepsis. However, the molecular mechanisms underlying α-HB's involvement in sepsis remain unclear. This study aims to explore the targets of α-HB and their association with sepsis progression using multi-database data mining, machine learning, and unsupervised clustering analyses.</p><p><strong>Methods: </strong>α-HB-related targets were identified through comprehensive data mining from three databases: SEA, SuperPred, and SwissTargetPrediction. Sepsis-related targets were obtained from the GEO dataset GSE26440, and the intersection of these datasets was analyzed to reveal common targets. Functional enrichment analysis, protein-protein interaction (PPI) network construction, and machine learning algorithms (L1-LASSO, RF, and SVM) were applied to identify biomarkers. Additionally, a nomogram was constructed to predict sepsis progression. Clustering, GSVA, and ssGSEA analyses were performed to explore sepsis subtypes. Molecular docking simulations was conducted to investigate interactions between α-HB and key targets.</p><p><strong>Results: </strong>A total of 42 common targets were identified between α-HB and sepsis, with significant enrichment in pathways related to immune response, hypoxia, and cancer. Machine learning-based feature selection identified four robust biomarkers (APEX1, CTSD, SLC40A1, PIK3CB) associated with sepsis. The constructed nomogram demonstrated high predictive accuracy for sepsis risk. Unsupervised clustering revealed two distinct α-HB-related sepsis subtypes with differential immune cell infiltration patterns and pathway activities, particularly involving immune and inflammatory pathways. Subtype 1 was predominantly associated with non-survivors, while Subtype 2 was more frequent among survivors, showing a significant difference in survival status. Molecular docking analysis further indicated potential interactions between α-HB and key targets (APEX1, CTSD, SLC40A1, PIK3CB), providing insights into the molecular mechanisms of α-HB in sepsis.</p><p><strong>Conclusion: </strong>This study identifies key α-HB-related targets and biomarkers for sepsis, offering new insights into its pathophysiology. The findings highlight the potential of α-HB in modulating immune responses and suggest that α-HB-related targets could serve as promising therapeutic targets for sepsis management.</p>","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":"16 ","pages":"1615269"},"PeriodicalIF":4.8,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12484119/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145212173","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 influence of targeted therapies in the inner ear.","authors":"Tony Bonilla, Jake DiFatta, Esperanza Bas Infante, Stefania Goncalves","doi":"10.3389/fphar.2025.1620679","DOIUrl":"10.3389/fphar.2025.1620679","url":null,"abstract":"<p><p>Scientific research has significantly propelled advancements in healthcare. One notable application is precision medicine, which seeks to analyze and comprehend disease pathology to offer personalized medical treatments to patients. Targeted oncology, a branch of precision medicine, focuses on identifying and targeting specific molecules that regulate cancer cells, thereby minimizing harm to healthy cells. Different types of targeted therapy against cancer include monoclonal antibodies and small molecules. This manuscript intends to provide an overview of the influence of these targeted oncology and non-oncology therapies on hearing. Furthermore, side effects including immune-related adverse events will be reviewed as potential causes of hearing deterioration in this patient population.</p>","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":"16 ","pages":"1620679"},"PeriodicalIF":4.8,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12484149/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145212257","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 development prospects of siRNA drugs for tumor therapy: analysis of clinical trial registration data from 2004 to 2024.","authors":"Cai-E Wang, Delong Zhen, Lukui Yang, Guifang Li","doi":"10.3389/fphar.2025.1637958","DOIUrl":"10.3389/fphar.2025.1637958","url":null,"abstract":"<p><strong>Background: </strong>This study systematically compares clinical trial patterns of siRNA drugs in oncology and non-oncology, aiming to inform optimized R&D strategies for oncology.</p><p><strong>Methods: </strong>Trial phases, sponsor countries, biomarkers, and targets were analyzed for global siRNA trials (2004-2024).</p><p><strong>Results: </strong>Non-oncology trial dominated (90% of 424 trials), peaking in 2021 (64 trials), and yielded 6 approved drugs for metabolic/genetic diseases. Key non-oncology targets included PCSK9 and HBV. Oncology trials initiated later, primarily focusing on phase I/II studies (60% phase I), targeting solid tumors (40%) and CSF2-related therapies (40%). Clinical trial activity in China commenced in 2019, demonstrating acceleration in 2023, yet overall trial volume remains lower than global benchmarks. Cross-target analysis has pinpointed PTGS2 and TGFB1 as shared targets, indicating the possibility for combination therapy.</p><p><strong>Conclusion: </strong>Overcoming technical challenges (e.g., targeted delivery) and exploiting multi-target synergies are critical to expanding siRNAs applications in oncology. Success in non-oncology settings demonstrates the translational potential of siRNA technology, however, oncology requires tailored strategies to address complex tumor biology and delivery barriers.</p>","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":"16 ","pages":"1637958"},"PeriodicalIF":4.8,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12484142/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145212190","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":"Cantharidin: a double-edged sword in medicine and toxicology.","authors":"Jie Zhang, Tongtong Tian, Canyu Li, Yong Liu, Yunyun Wang, Ling Liu, Liang Liu, Yufeng Yao","doi":"10.3389/fphar.2025.1644186","DOIUrl":"10.3389/fphar.2025.1644186","url":null,"abstract":"<p><p>Cantharidin (CTD), a natural terpenoid toxin secreted by blister beetles, acts as a potent inhibitor of protein phosphatase. As the principal active component of Mylabris, a traditional Chinese medicine, CTD has attracted considerable interest due to its dual properties, combining potent anti-tumor activity with significant toxicity. Contemporary pharmacological research demonstrates that CTD inhibits the growth and proliferation of diverse cancer cells lines. It exhibits antibacterial and antiparasitic properties, and demonstrates pesticidal activity in agricultural applications. Despite these benefits, CTD exhibits a prominent double-edged profile, marked by severe toxic effects, including cardiotoxicity, nephrotoxicity, gastrointestinal toxicity, and reproductive toxicity. Our prior research has identified the heart and liver as primary targets of CTD's acute toxicity, where it induces apoptosis and necrosis of cardiomyocytes and hepatocytes. Recent efforts to mitigate its toxicity while preserving efficacy have focused on the structural modifications of CTD and the development of its derivatives. Additionally, CTD has been demonstrated to enhance anti-tumor efficacy when combined with other drugs, particularly against certain drug-resistant tumors. This review comprehensively evaluates CTD's pharmacology and toxicology, synthesizes pertinent toxicological data, and explores strategies for toxicity reduction to guide future research.</p>","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":"16 ","pages":"1644186"},"PeriodicalIF":4.8,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12487651/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145212222","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":"Correction: Resveratrol and Angiogenin-2 combined with PEGDA/TCS hydrogel for the targeted therapy of hypoxic bone defects via activation of the autophagy pathway.","authors":"Dehui Fan, Hengping Liu, Zhenning Zhang, Meiyi Su, Zhixian Yuan, Ying Lin, Shuquan Yang, Wenqiang Li, Xintao Zhang","doi":"10.3389/fphar.2025.1597755","DOIUrl":"https://doi.org/10.3389/fphar.2025.1597755","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.3389/fphar.2021.618724.].</p>","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":"16 ","pages":"1597755"},"PeriodicalIF":4.8,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12487011/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145212177","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":"Toxicological assessment of novel Anti-COVID traditional Chinese medicine formulae NRICM101 and NRICM102: a comprehensive study on safety and genotoxicity.","authors":"Chun-Tang Chiou, Chao-Lin Chang, Yu-Hwei Tseng, Geng-You Liao, Jiunn-Wang Liao, Yuh-Chiang Shen, Wen-Chi Wei, Keng-Chang Tsai, Yu-Ching Huang, Wen-Chiung Chang, Wen-Fei Chiou, Chia-Ching Liaw, Yi-Chang Su","doi":"10.3389/fphar.2025.1596369","DOIUrl":"10.3389/fphar.2025.1596369","url":null,"abstract":"<p><p>Although the first outbreak of COVID-19 occurred in 2019, the virus continues to circulate globally, even years later. In Taiwan, the novel traditional Chinese medicine formulas, NRICM101 and NRICM102, have been extensively used to treat COVID-19, with Chinese medicine practitioners frequently prescribing them to manage the disease. According to data from the Taiwan Centers for Disease Control, approximately 22% of COVID-19 patients opted for NRICMs' treatments between 2021 and 2022. Despite the widespread use and reported effectiveness of these treatments, it is critical to evaluate the potential risks associated with their prolonged or frequent use. In this study, we conducted a comprehensive toxicological assessment of NRICM101 and NRICM102. Acute oral toxicity was evaluated by administering a single 5 g/kg bw dose to ICR mice and SD rats. No mortality, sex-related differences, or clinical signs of toxicity were observed. Subchronic toxicity was assessed through a 28-day repeated oral administration study with doses of 1.6, 3.1, and 4.8 g/kg bw per day of NRICM101 or 102, which showed no treatment-related deaths or organ pathology. While some hematological changes were noted, they were generally within physiological ranges and showed no consistent dose-dependent trends. Genotoxicity was assessed using three standard assays. The Ames test revealed no mutagenic activity. The <i>in vitro</i> mouse lymphoma assay showed genotoxicity only at the highest concentration (5.0 mg/mL) and only in the absence of S9 metabolic activation, suggesting a context-dependent response possibly linked to direct-acting or cytotoxic effects at excessive doses. In contrast, the <i>in vivo</i> micronucleus assay, which reflects systemic genotoxicity under physiologically relevant conditions, showed negative results. Together, these findings indicate that NRICM101 and NRICM102 are not associated with acute or subchronic toxicity at clinically relevant doses and durations, and they present a low genotoxic risk under standard conditions of use. Nonetheless, further long-term and pharmacokinetic studies are warranted to fully characterize their safety profiles, particularly with high-dose or prolonged administration.</p>","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":"16 ","pages":"1596369"},"PeriodicalIF":4.8,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12484172/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145212195","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}