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Irisin attenuates tubular epithelial ferroptosis in diabetic kidney disease by inhibiting the HMGB1/Nrf2/GPX4 pathway. 鸢尾素通过抑制HMGB1/Nrf2/GPX4通路减轻糖尿病肾病小管上皮铁下垂。
IF 3.1 4区 医学
Naunyn-Schmiedeberg's archives of pharmacology Pub Date : 2025-10-17 DOI: 10.1007/s00210-025-04681-z
Dan Wang, Furong Zhu, Miao Miao Shao, Huimei Zang, Xue Xia
{"title":"Irisin attenuates tubular epithelial ferroptosis in diabetic kidney disease by inhibiting the HMGB1/Nrf2/GPX4 pathway.","authors":"Dan Wang, Furong Zhu, Miao Miao Shao, Huimei Zang, Xue Xia","doi":"10.1007/s00210-025-04681-z","DOIUrl":"https://doi.org/10.1007/s00210-025-04681-z","url":null,"abstract":"<p><p>Diabetic nephropathy (DN) is a global health threat with limited therapeutic interventions. Irisin, a myokine derived from FNDC5, has been implicated in glucose homeostasis and anti-diabetic effects; however, its precise mechanistic role in glucose metabolism regulation remains elusive. This study elucidates the specific role of Irisin in mitigating diabetic renal tubular epithelial injury, with a focus on its regulatory mechanisms under glucotoxic conditions. Utilizing streptozotocin (STZ)-induced type 1 diabetes (T1D) mouse models and high glucose (HG)-stimulated HK-2 cells, we demonstrated that STZ-induced DN mice exhibited renal dysfunction, oxidative stress, and iron accumulation. Sustained HG exposure downregulated glutathione peroxidase 4 (GPX4) and xCT while upregulating Ptgs2 and FPN1, indicative of Ferroptosis initiation. Irisin treatment significantly attenuated these pathological changes and ameliorated renal tubular epithelial injury. Mechanistically, this protective effect was mediated through the activation of high-mobility group box-1 (HMGB1), a damage-associated regulator, as observed in both in vivo and in vitro studies. Furthermore, we identified the nuclear translocation of Nrf2 and its downstream target GPX4 in vitro. Specific interference with Nrf2, through both knockdown and overexpression experiments under HG conditions, further demonstrated Irisin's regulatory role on HMGB1. This was validated by assessing tubular epithelial cell viability, alongside cellular levels of malondialdehyde (MDA), glutathione (GSH), superoxide dismutase (SOD), and Fe<sup>2+</sup> content. Notably, Nrf2 co-transfection nullified the protective effects of Irisin, exacerbating Ferroptosis markers. Collectively, our findings reveal that Irisin protects against glucotoxicity-induced renal injury by inhibiting tubular epithelial Ferroptosis via the HMGB1/Nrf2/GPX4 axis, thereby proposing a novel therapeutic target for DN.</p>","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145308432","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}
引用次数: 0
Genkwanin alleviates paraquat-induced acute lung injury by activating SIRT1-mediated Nrf2/HO-1 signaling pathway. Genkwanin通过激活sirt1介导的Nrf2/HO-1信号通路减轻百草枯诱导的急性肺损伤。
IF 3.1 4区 医学
Naunyn-Schmiedeberg's archives of pharmacology Pub Date : 2025-10-17 DOI: 10.1007/s00210-025-04685-9
Shuzhen Liu, Lei He, Yang Yuan, Guangzhi Wang, Wenhua Qin
{"title":"Genkwanin alleviates paraquat-induced acute lung injury by activating SIRT1-mediated Nrf2/HO-1 signaling pathway.","authors":"Shuzhen Liu, Lei He, Yang Yuan, Guangzhi Wang, Wenhua Qin","doi":"10.1007/s00210-025-04685-9","DOIUrl":"https://doi.org/10.1007/s00210-025-04685-9","url":null,"abstract":"<p><p>Paraquat (PQ) mainly damages the lungs, leading to acute lung injury (ALI) and even pulmonary fibrosis. Genkwanin (GEN) is demonstrated to possess anti-inflammatory and antioxidant activities in several diseases. This study aims to elucidate the protective effect of GEN against PQ-induced ALI and to decipher its underlying molecular mechanism. C57BL/6 J mice were injected intraperitoneally with 20 mg/kg PQ to induce an in vivo ALI model. BEAS-2B cells were treated with PQ to mimic an in vitro ALI model. The results showed that GEN alleviated PQ-induced lung pathologic damage, lung injury score, wet/dry weight ratio, myeloperoxidase (MPO) activity, and inflammatory cytokine production. GEN inhibited the expression of malondialdehyde (MDA) and 4-hydroxynonenal (4-HNE) and enhanced the activities of superoxide dismutase (SOD) and catalase (CAT) in lung tissues of PQ-treated mice. Also, GEN decreased PQ-induced apoptosis of lung tissues by downregulating Bax and Cleaved caspase 3 and elevating Bcl-2. Moreover, GEN repressed inflammatory factor levels, reactive oxygen species (ROS) production, and apoptosis in PQ-stimulated BEAS-2B cells. Additionally, GEN treatment led to the increase of sirtuin 1 (SIRT1) expression in both PQ-treated mice and BEAS-2B cells. Inhibition of SIRT1 largely reversed the inhibitory effects of GEN on PQ-induced inflammation, oxidative stress, and apoptosis in mice and cells. Furthermore, GEN activated the Nrf2/HO-1 signaling by upregulating SIRT1 in mice and BEAS-2B cells administered with PQ. In conclusion, GEN ameliorates lung inflammation, oxidative stress, and apoptosis in PQ-induced ALI by inducing SIRT1 to activate the Nrf2/HO-1 signaling. Our findings highlight the potential of GEN to resist PQ poisoning.</p>","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145308377","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}
引用次数: 0
Sex differences in the response to treatment of attention deficit hyperactivity disorder. 注意缺陷多动障碍治疗反应的性别差异。
IF 3.1 4区 医学
Naunyn-Schmiedeberg's archives of pharmacology Pub Date : 2025-10-16 DOI: 10.1007/s00210-025-04716-5
Elisa D Müller, Anke C Fender
{"title":"Sex differences in the response to treatment of attention deficit hyperactivity disorder.","authors":"Elisa D Müller, Anke C Fender","doi":"10.1007/s00210-025-04716-5","DOIUrl":"https://doi.org/10.1007/s00210-025-04716-5","url":null,"abstract":"<p><p>Attention deficit hyperactivity disorder (ADHD) impacts markedly on juvenile development and daily function of young and adult patients. Global prevalence and drug prescription rates are consistently on the rise, particularly in young women. Personal experience in daily psychotherapy practice supports sex differences in how the disorder manifests and how the patients respond to treatment. We review sex differences in therapeutic and adverse responses to the cornerstone ADHD pharmacotherapies methylphenodate and amphetamines, under consideration of preclinical mechanistic insights, clinical studies, and relevance for real-life psychotherapy practice. Overall, many gaps in knowledge remain regarding sex differences on all levels of ADHD disease manifestation, diagnosis, and therapy, and the underlying mechanistic basis. Certain treatment strategies may be more or less appropriate, safe, and effective in specific patients, an aspect which warrants further attention in future guideline reforms.</p>","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145302063","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}
引用次数: 0
Integrated bioinformatics and molecular docking ıdentify CCNB1, CDK1, and CYP1A2 as therapeutic targets of phytochemicals in hepatocellular carcinoma. 整合生物信息学和分子对接ıdentify CCNB1、CDK1和CYP1A2作为植物化学物质治疗肝癌的靶点。
IF 3.1 4区 医学
Naunyn-Schmiedeberg's archives of pharmacology Pub Date : 2025-10-16 DOI: 10.1007/s00210-025-04729-0
Murat Isıyel, Hamid Ceylan, Yeliz Demir
{"title":"Integrated bioinformatics and molecular docking ıdentify CCNB1, CDK1, and CYP1A2 as therapeutic targets of phytochemicals in hepatocellular carcinoma.","authors":"Murat Isıyel, Hamid Ceylan, Yeliz Demir","doi":"10.1007/s00210-025-04729-0","DOIUrl":"https://doi.org/10.1007/s00210-025-04729-0","url":null,"abstract":"<p><p>Hepatocellular carcinoma (HCC) is a globally prevalent malignancy and a leading cause of cancer-related mortality; robust prognostic biomarkers and actionable therapeutic strategies are urgently needed. This study aimed to identify potential diagnostic and therapeutic gene targets in HCC through integrated transcriptomic and bioinformatics analyses. Specifically, we integrated four GEO microarray datasets to derive consensus differentially expressed genes (DEGs), constructed a high-confidence protein-protein interaction network, and prioritized hub genes using multiple CytoHubba topological metrics. To explore pharmacological relevance, hub genes were cross-referenced with known targets of four bioactive compounds (metformin, curcumin, resveratrol, silymarin) from the Comparative Toxicogenomics Database; in-silico validations (GEPIA2, UALCAN, TIMER) and molecular docking were then performed. We identified 290 consensus DEGs and seven hub genes, among which CCNB1 and CDK1 were upregulated while CYP1A2 was downregulated and selected as key candidates. Gene ontology and KEGG analyses implicated these genes in cell cycle progression and p53 signaling. Immune-infiltration analysis showed positive associations between CCNB1/CDK1 expression and innate immune cell infiltration, whereas CYP1A2 correlated negatively. Molecular docking revealed favorable binding affinities between the selected compounds and target proteins. Collectively, our results suggest CCNB1 and CDK1 as potential oncogenic markers and CYP1A2 as a putative tumor suppressor in HCC, warranting further functional validation for diagnostic and therapeutic development.</p>","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145302047","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}
引用次数: 0
Inhibition of junctional protein disruption by 2,4,6-trihydroxy-3-geranyl acetophenone in lipopolysaccharide-induced endothelial hyperpermeability via GEF-H1/RhoA/ROCK pathway. 2,4,6-三羟基-3-香叶基苯乙酮通过GEF-H1/RhoA/ROCK途径抑制脂多糖诱导的内皮细胞高通透性中连接蛋白的破坏。
IF 3.1 4区 医学
Naunyn-Schmiedeberg's archives of pharmacology Pub Date : 2025-10-16 DOI: 10.1007/s00210-025-04627-5
Yee Han Chan, Kong Yen Liew, Kamal Rullah, Hanis Hazeera Harith, Ji Wei Tan, Daud Ahmad Israf, Khozirah Shaari, Mexmollen Marcus, Chau Ling Tham
{"title":"Inhibition of junctional protein disruption by 2,4,6-trihydroxy-3-geranyl acetophenone in lipopolysaccharide-induced endothelial hyperpermeability via GEF-H1/RhoA/ROCK pathway.","authors":"Yee Han Chan, Kong Yen Liew, Kamal Rullah, Hanis Hazeera Harith, Ji Wei Tan, Daud Ahmad Israf, Khozirah Shaari, Mexmollen Marcus, Chau Ling Tham","doi":"10.1007/s00210-025-04627-5","DOIUrl":"https://doi.org/10.1007/s00210-025-04627-5","url":null,"abstract":"<p><p>2,4,6-Trihydroxy-3-geranyl acetophenone (tHGA) is a bioactive phloroglucinol compound found in the leaves of Melicope pteleifolia (Champ. ex Benth.) T.G.Hartley. Our previous study has proven that tHGA exhibited significant in vitro barrier protective effects against lipopolysaccharide (LPS) induction, mainly by inhibiting endothelial hyperpermeability via attenuation of F-actin cytoskeletal rearrangement, as F-actin cytoskeleton is anchored to junctional proteins such as zonula occluden (ZO)-1, occludin, and vascular endothelial-cadherin (VE-cadherin), and they play collaborative roles in the preservation of endothelial integrity. Therefore, the effects of tHGA on these junctional proteins were further investigated, followed by the dissection of signalling pathways mediated by tHGA in suppressing LPS-induced junctional protein disruption during endothelial hyperpermeability. HUVECs were pretreated with tHGA prior to LPS induction. TEER, immunofluorescence staining, Western Blotting, and RT-qPCR were performed to examine the effects of tHGA on junctional proteins in terms of their integrity, localization, protein expression, and gene expression, respectively. Proinflammatory signalling molecules including MLC, NF-κB p65, p38 MAPK, ERK MAPK, and JNK MAPK were assessed to unravel the underlying signalling pathways, followed by molecular docking on human ROCK1 to predict the molecular target of tHGA. tHGA profoundly preserved junctional integrity by inhibiting both delocalization and downregulation of ZO-1, occludin, and VE-cadherin, via inactivation of MLC, NF-κB p65, p38 MAPK, and ERK MAPK, which are mainly diverged from GEF-H1/RhoA/ROCK pathway. ROCK1 was predicted as the molecular target of tHGA. tHGA should be developed as a potential therapeutic remedy for prevention and/or treatment of permeability-related disorders.</p>","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145301978","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}
引用次数: 0
Natural product-based interventions for thyroid disorders: mechanisms and applications. 天然产品为基础的干预甲状腺疾病:机制和应用。
IF 3.1 4区 医学
Naunyn-Schmiedeberg's archives of pharmacology Pub Date : 2025-10-16 DOI: 10.1007/s00210-025-04604-y
Radwa H El-Akad, Ahmed H Elosaily, Noha M Gamil, Rana M Merghany, Riham A El-Shiekh, Wesam Taher Almagharbeh, Hebatollah E Eitah
{"title":"Natural product-based interventions for thyroid disorders: mechanisms and applications.","authors":"Radwa H El-Akad, Ahmed H Elosaily, Noha M Gamil, Rana M Merghany, Riham A El-Shiekh, Wesam Taher Almagharbeh, Hebatollah E Eitah","doi":"10.1007/s00210-025-04604-y","DOIUrl":"https://doi.org/10.1007/s00210-025-04604-y","url":null,"abstract":"<p><p>Thyroid diseases are widespread endocrine disorders that affect a significant portion of the global population. The pathology associated with specific types or stages of thyroid disease is complex and intricately linked to various biological functions. While the mortality rate associated with thyroid dysfunction is relatively low, it can lead to metabolic and immunological disorders that result in considerable discomfort for affected individuals. Currently, numerous pharmaceutical options are available for managing thyroid disease; however, issues such as drug toxicity and prolonged treatment durations highlight the urgent need for more effective alternatives. In this review, we conducted a comprehensive literature search to explore the use of herbs and herbal formulations in the treatment of thyroid diseases. Our findings underscore the potential of these natural remedies in drug discovery efforts. It is evident that further scientific investigation into the mechanisms of action of these medicinal plants is crucial for validating their traditional applications. By enhancing our understanding of how these natural products function, we can pave the way for innovative therapeutic strategies that may improve outcomes for individuals suffering from thyroid disorders.</p>","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145301971","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}
引用次数: 0
Tenuigenin targets Trim31 and NF-κB pathway to protect dopaminergic neurons in Parkinson's disease mice. Tenuigenin靶向Trim31和NF-κB通路保护帕金森病小鼠多巴胺能神经元。
IF 3.1 4区 医学
Naunyn-Schmiedeberg's archives of pharmacology Pub Date : 2025-10-16 DOI: 10.1007/s00210-025-04707-6
Di Zhang, Chen Xu, Borui Tang, Yuyang Dai, Shaojie Guo, Zitong Fu, Zheng Fan, Xiuli Zhao
{"title":"Tenuigenin targets Trim31 and NF-κB pathway to protect dopaminergic neurons in Parkinson's disease mice.","authors":"Di Zhang, Chen Xu, Borui Tang, Yuyang Dai, Shaojie Guo, Zitong Fu, Zheng Fan, Xiuli Zhao","doi":"10.1007/s00210-025-04707-6","DOIUrl":"https://doi.org/10.1007/s00210-025-04707-6","url":null,"abstract":"<p><p>Parkinson's disease (PD) is a neurodegenerative disorder characterized by the progressive loss of dopaminergic (DA) neurons in the SN and the accumulation of α-synuclein (α-syn). In this study, we explored the neuroprotective effects of the natural compound tenuigenin on PD through bioinformatics analysis and in vivo experiments. We analyzed GEO datasets GSE99039 and GSE7307 and found that the expression of trim31 was significantly decreased in both peripheral blood and substantia nigra (SN) tissues of PD patients. Using a PD mouse model with overexpressed human α-syn in SN, we also discovered that tenuigenin treatment significantly reversed the downregulation of trim31. And the finding was further validated by quantitative proteomics, RT-qPCR, and Western blotting. Gene ontology (GO) enrichment analysis revealed that differentially expressed genes (DEGs) can enrich in the pathway of \"positive regulation of NF-κB transcription factor activity.\" Tenuigenin treatment also effectively suppressed NF-κB upregulation in the SN of PD mice, reduced TNF-α expression and microglial activation, which suggesting that its neuroprotective effects may be mediated through inhibiting NF-κB-induced neuroinflammation. Additionally, tenuigenin exhibited significant protective effects on DA neurons. Our results indicate that tenuigenin targets trim31 as a key regulator and modulates the pathways of NF-κB to achieve anti-inflammatory and neuroprotective effects. Therefore, tenuigenin holds promise as a potential therapeutic candidate for PD.</p>","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145301998","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}
引用次数: 0
Curative potential of resveratrol and pterostilbene against epoxy resin-induced reproductive toxicity in female rats. 白藜芦醇和紫檀芪对环氧树脂致雌性大鼠生殖毒性的治疗作用。
IF 3.1 4区 医学
Naunyn-Schmiedeberg's archives of pharmacology Pub Date : 2025-10-15 DOI: 10.1007/s00210-025-04629-3
Sidra Malik, Ammara Saleem, Qurat-Ul-Ain, Muhammad Imran Khan, Zulcaif Ahmad, Syeda Momna Ishtiaq, Muhammad Furqan Akhtar
{"title":"Curative potential of resveratrol and pterostilbene against epoxy resin-induced reproductive toxicity in female rats.","authors":"Sidra Malik, Ammara Saleem, Qurat-Ul-Ain, Muhammad Imran Khan, Zulcaif Ahmad, Syeda Momna Ishtiaq, Muhammad Furqan Akhtar","doi":"10.1007/s00210-025-04629-3","DOIUrl":"https://doi.org/10.1007/s00210-025-04629-3","url":null,"abstract":"<p><p>Epoxy resin is the precursor of bisphenol A and is an important component in a wide range of daily used products. It produces toxic effects by oxidative stress, inflammation and endocrine disruption. Its exposure to humans occur through inhalation, dermal contact and ingestion. Several studies link the epoxy resin components to reproductive toxicity including impaired ovarian function and hormonal imbalance in males and females. The study was aimed to assess the reproductive toxicity in female rats due to epoxy resin exposure and demonstrate the curative potential of resveratrol and pterostilbene against epoxy resin-induced reproductive toxicity. The study included eight groups of rats (n = 6). One was the control group receiving only vehicle, while the other one was the epoxy resin-treated group in which the female rats were given orally epoxy resin at 15 mg/kg/day for 4 weeks. Other six groups were administered resveratrol and pterostilbene orally at different doses (50, 25 and 12.5 mg/kg/day) for 4 weeks. Dose selection was performed according to the previously published data. After the study duration, female rats were ovariectomized and assessed for body weight changes, oxidative stress and histopathological changes. ELISA analysis was performed for inflammatory markers in ovaries while caspase-3 gene was evaluated in ovaries by PCR. Statistical comparison was performed by one-way ANOVA followed by Tukey's post hoc test. The subsequent treatment with resveratrol and pterostilbene depicted marked improvements in LH, FSH, estrogen, progesterone and testosterone levels. The female rats exposed to epoxy resin showed a high content of the caspase-3 gene responsible for apoptosis. Moreover, the oxidative stress markers such as SOD, CAT and GSH were increased while MDA decreased in the ovary of rats treated with resveratrol and pterostilbene, whereas anti-inflammatory markers such as TNF-α and NF-κB were increased significantly with the epoxy resin exposure but treatment drugs employed reduction in their levels significantly. It was concluded that epoxy resin produced marked damage to the ovary and this toxicity can be reduced with resveratrol and pterostilbene treatments.</p>","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145292949","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}
引用次数: 0
Metformin-mediated modulation of epigenetic regulators in type 2 diabetes: A study on differential expression of DNMT1, TET1, OGG1, and AID genes. 二甲双胍介导的2型糖尿病表观遗传调节因子:DNMT1、TET1、OGG1和AID基因差异表达的研究
IF 3.1 4区 医学
Naunyn-Schmiedeberg's archives of pharmacology Pub Date : 2025-10-15 DOI: 10.1007/s00210-025-04700-z
Sadaf Moeez, Syeda Kiran Riaz, Tanveer Ahmed Qaiser, Juneda Sarfraz, Asif Naseer, Shafiul Haque
{"title":"Metformin-mediated modulation of epigenetic regulators in type 2 diabetes: A study on differential expression of DNMT1, TET1, OGG1, and AID genes.","authors":"Sadaf Moeez, Syeda Kiran Riaz, Tanveer Ahmed Qaiser, Juneda Sarfraz, Asif Naseer, Shafiul Haque","doi":"10.1007/s00210-025-04700-z","DOIUrl":"https://doi.org/10.1007/s00210-025-04700-z","url":null,"abstract":"<p><p>Type 2 diabetes mellitus (T2DM) is a widespread medical condition characterized by high blood glucose and inadequate insulin action, ultimately leading to insulin resistance. Genetic, epigenetic, and non-genetic factors are known to influence the pathogenesis of T2DM. Epigenetic alterations, principally DNA methylation and demethylation dynamics, play an important role, yet, their molecular mechanisms remain poorly understood. The present study aimed to study the expression patterns of DNMT1, TET1, OGG1, and AID genes involved in epigenetic regulation and insulin resistance in T2DM patients, along with in vitro validation using HepG2 insulin-resistant cell models. Blood samples were collected from 160 T2DM patients, categorized as metformin responders and non-responders, along with 40 healthy controls. Insulin resistance was induced in HepG2 cells, which were then treated with metformin and sulfonylureas at various concentrations and time intervals. qPCR was performed to study the differential expression of DNMT1, TET1, OGG1, and AID genes, using GAPDH as an internal control. Statistical analysis was done using SPSS software. Our results indicate that the expression of DNMT1, TET1, OGG1, and AID was significantly higher in T2DM metformin non-responders compared to T2DM metformin responders (P < 0.0001). Furthermore, we found that metformin treatment led to the down-expression of these genes in insulin-resistant HepG2 cells thus proving their in the regulation of the epigenetics state. This study highlights the contribution of epigenetic mechanisms in the pathogenesis of T2DM and underscores the therapeutic role of metformin in modulating key epigenetic regulators, precisely by altering DNA methylation/demethylation pathways through the regulation of key gene. These findings suggest that DNMT1, TET1, OGG1, and AID may serve as potential biomarkers and therapeutic targets for the management of T2DM.</p>","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145292986","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}
引用次数: 0
Brevi-inflammin: novel actinobacterial COX-2 inhibitor for alleviating rheumatoid arthritis inflammation. 短期炎症:新型放线菌COX-2抑制剂,缓解类风湿关节炎炎症。
IF 3.1 4区 医学
Naunyn-Schmiedeberg's archives of pharmacology Pub Date : 2025-10-15 DOI: 10.1007/s00210-025-04654-2
Vishnupriya Chandrasekaran, Kavitha Rangasamy
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