Journal of Biochemical and Molecular Toxicology最新文献

{"title":"Inhibition of Malate Dehydrogenase-Pyruvate-cPLA2-Reduced ROS and Recovery From Ischemia-Reperfusion Injury","authors":"Undurti N. Das","doi":"10.1002/jbt.70388","DOIUrl":"https://doi.org/10.1002/jbt.70388","url":null,"abstract":"","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 7","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144589601","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect of Imidazole Derivatives on U-87 MG Glioblastoma Cell Lines via TrxR1, GST and GR, Antimicrobial and Antioxidant Activities","authors":"Işıl Nihan Korkmaz,&nbsp;Arzu Öztürk Kesebir","doi":"10.1002/jbt.70376","DOIUrl":"https://doi.org/10.1002/jbt.70376","url":null,"abstract":"<div>\u0000 \u0000 <p>In the literature, it is seen that heteroaromatic imidazole compounds have many effective biological properties such as antitumor, antimicrobial, antioxidant, antihypertensive, antiallergic, anticancer, analgesic and anti-inflammatory. Due to these effects, its therapeutic effects in various types of cancer are being investigated more and more day by day. In particular, the effects of imidazole derivatives are being investigated for cancer types for which no treatment has yet been identified, such as Glioblastoma Multiforme (GBM). For this reason, the anticancer effects of imidazole derivatives on U-87 MG and HDFa cells, their inhibitory effects on TrxR1, GR and GST enzymes associated with multidrug resistance in cancer cells, and their antioxidant and antimicrobial activities were investigated. Cytotoxic effects were measured by MTT assay after U-87 MG HDFa cells were treated with imidazole compounds. The results revealed that imidazole compounds decreased the viability of cells in a dose-dependent manner compared to the control group. In addition, when imidazole compounds are used in treatments targeting enzymes in cancerous cells, it has been observed that they do not harm healthy HDFa cells, but they also have a significant effect on U-87 MG cells. It can be said that compound I3 is a selective inhibitor in the treatment of Glioblastoma. It was observed that compounds I2 and I3 have antimicrobial activity. When the antioxidant activities of imidazole derivatives were examined, we observed that compounds I2 and I3 exhibited antioxidant activity. These results show us that imidazole molecules have antioxidant, antimicrobial and anticancer effects.</p></div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 7","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144573255","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Anticancer Activity of Fisetin via KEAP1, DNMT1, and mTOR Axis Against Colon Cancer: An Integrated In Silico, In Vitro, and In Vivo Approach","authors":"Satyam Sharma,&nbsp;Rajat Mudgal,&nbsp;Sairam Krishnamurthy,&nbsp;Sanjiv Singh","doi":"10.1002/jbt.70391","DOIUrl":"https://doi.org/10.1002/jbt.70391","url":null,"abstract":"<div>\u0000 \u0000 <p>The proliferation of colon cancer is influenced by alterations in epigenetic, reactive oxygen species (ROS), and dysregulation of signaling pathways, especially via the involvement of DNMT1, mTOR, and KEAP1 axis. The current investigation examined the antiproliferative capabilities of fisetin (FisT) in a rat model and in colon cancer cell lines HCT116, CT-26, and Caco-2. Our findings show that FisT modulated the DNMT1, mTOR, KEAP1, and IL-6 signaling pathways to enhance the antiproliferative effects against in vitro and in vivo preclinical model. In-silico based anticancer potential of fisetin were revealed through SwissTargetPrediction, Cytoscape, STRING, Schrodinger, molecular dynamics simulations, KEGG, and network analysis. In-vitro MTT assay, cell cycle analysis, ROS level, immunocytofluorescence, western blot analysis, and in vivo immunohistofluorescence, western blot analysis, ELISA-based assays were performed to evaluate anticancer property of fisetin. Our findings revealed that FisT has a strong anticancer property by demethylating DNA, enhancing ROS, KEAP1 level. Simultaneously downregulated the DNMT1 &amp; mTOR expression, and preventing angiogenesis, cell proliferation, invasion, and migration against in vitro &amp; in vivo models. FisT enhances the anticancer response of tumor development and reduces the size of crypt foci. FisT has potential as a cytotoxic drug, improving and intensifying anticancer responses in colon cancer.</p></div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 7","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144550856","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Wogonin Inhibits Oxidative Stress in Hypoxia-Induced hCMEC/D3 Cells Through Suppressing CXCL8-Mediated TLR4/NF-κB Pathway","authors":"Tianbo Jin,&nbsp;Baoping Hu,&nbsp;Tianyi Zhang,&nbsp;Jing Wang,&nbsp;Dongfeng Zhang,&nbsp;Yemeng Sheng,&nbsp;Li Wang","doi":"10.1002/jbt.70390","DOIUrl":"https://doi.org/10.1002/jbt.70390","url":null,"abstract":"<div>\u0000 \u0000 <p>High-altitude cerebral edema (HACE) is a critical neurological disorder with limited treatment options. Wuwei Shaji San (WWSHS), a traditional Chinese medicine formula, demonstrates therapeutic potential for HACE, yet its mechanisms remain unclear. This study explores the molecular mechanism of WWSHS in HACE treatment. Network pharmacology was performed to identify core active ingredients and targets of WWSHS against HACE. Protein-protein interaction (PPI) networks, functional enrichment analysis, and molecular docking were performed. Hypoxia-induced injury in hCMEC/D3 cells was used to validate wogonin's effects. Apoptosis, oxidative stress indicators (ROS, H₂O₂, MDA, SOD, LDH), and inflammation factors (IL-6, IL-1β, TNF-α) were evaluated via flow cytometry, biochemical assays, and qPCR. CXCL8 overexpression and TLR4 inhibitor (Resatorvid) were applied to investigate mechanisms. Network analysis revealed 63 shared targets between WWSHS and HACE, with CXCL8 as a central target and wogonin as the core ingredients. Molecular docking confirmed strong binding between wogonin and CXCL8 (−7.6 kcal/mol). In vitro studies revealed that wogonin effectively mitigated hypoxia-induced cytotoxic effects, apoptotic responses, and oxidative stress in hCMEC/D3 cells. The mechanistic investigation demonstrated that wogonin downregulated CXCL8 expression, consequently attenuating TLR4/NF-κB signaling activation. Notably, CXCL8 overexpression counteracted wogonin's cytoprotective properties against hypoxic damage. Complementary experiments showed that co-administration with resatorvid, a pharmacological TLR4 inhibitor, potentiated wogonin's therapeutic efficacy. Our findings suggest that wogonin may serve as a potential therapeutic agent for HACE by targeting CXCL8 and modulating the TLR4/NF-κB pathway, thereby reducing inflammation and oxidative stress.</p></div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 7","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144550858","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Embelin Ameliorates Diethylnitrosamine-Induced Liver Injury Through Down-Regulation of Apoptosis, Oxidative Stress and Inflammation by Influencing the Shh/Gli1 Signaling Pathways","authors":"Aydın Akcilar,&nbsp;Hikmet Keles,&nbsp;Raziye Akcilar,&nbsp;Fatma Emel Kocak","doi":"10.1002/jbt.70389","DOIUrl":"https://doi.org/10.1002/jbt.70389","url":null,"abstract":"<div>\u0000 \u0000 <p>Diethylnitrosamine (DEN) is a highly toxic compound with teratogenic, mutagenic, and carcinogenic properties. Embelin, a natural benzoquinone derived from Embelia ribes, has shown potential therapeutic effects. This study evaluated embelin's impact on biochemical, histopathological, and gene expression changes in DEN-induced liver injury. Twenty-eight male Wistar albino rats were assigned to four groups: Sham, Embelin (E), DEN, and DEN + E. DEN groups received a single intraperitoneal dose of 200 mg/kg DEN, while E and DEN + E groups were administered 1.2 mg/kg embelin for 14 days. Liver enzyme levels, lipid profiles, total antioxidant status (TAS), and total oxidant status (TOS) were measured. RT-PCR analysis was performed to assess sonic hedgehog (<i>Shh, Ptch1, Smo, Gli1</i>), inflammatory (<i>TNF-α, IL-6, IL-1β</i>) and apoptotic (<i>Tp53, casp3, Bcl-2, Bax</i>) gene expression in liver tissue. Histopathological examination showed that DEN induced fibrosis, congestion, apoptosis, and bile pigment accumulation, which were significantly mitigated by embelin. Embelin decreased liver enzyme and lipid levels, increased the activity of TAS, which is an antioxidant capacity, decreased the gene expression levels of pro-inflammatory cytokines <i>TNF-α, IL-6, IL-1β</i>, and the activation of the Shh signaling pathway. It also increased the expression of <i>Bcl-2</i> and decreased the gene expression levels of <i>Tp53, Casp3</i>, <i>Bax</i>, and inhibited liver apoptosis. These results imply that embelin may have a therapeutic effect on DEN-induced liver damage by preventing degenerative liver problems, regulating liver functions, suppressing oxidative stress, the inflammatory and apoptotic response, and modulating the Shh signaling pathways.</p></div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 7","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144550859","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Telmisartan Ameliorates Hypertension-Induced Kidney Damage by Restoring Glomerular Endothelial Barrier Function","authors":"Qiongqiong Guo,&nbsp;Junxia Wang","doi":"10.1002/jbt.70377","DOIUrl":"https://doi.org/10.1002/jbt.70377","url":null,"abstract":"<div>\u0000 \u0000 <p>Hypertension-induced renal injury arises from endothelial dysfunction and elevated glomerular permeability. Telmisartan, an Angiotensin II (Ang II) receptor blocker (ARB), is commonly used to treat hypertension and is known for its long-lasting effects, as well as its antioxidant and anti-inflammatory properties. However, the effects of Telmisartan on glomerular permeability are less well-documented. This study investigates the protective effects of Telmisartan (TEL), an Ang II receptor blocker, on hypertension-induced kidney damage. Using a mouse model of Angiotensin II/high salt (ANG/HS)-induced hypertension, TEL treatment significantly reduced mean arterial pressure, alleviated renal fibrosis, and improved kidney function, as indicated by lower urinary albumin and serum creatinine levels. TEL also suppressed oxidative stress and reduced the expression of inflammatory markers interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in renal tissues. Furthermore, TEL restored the expression of the tight junction protein zonula occludens-1 (ZO-1) in the glomeruli, which was downregulated in ANG/HS-treated mice. <i>In vitro</i> studies on human renal glomerular endothelial cells (HrGECs) confirmed that TEL reduced endothelial monolayer permeability and restored ZO-1 expression, effects that were mediated by Krüppel-like factor 4 (KLF4). These findings suggest that TEL mitigates glomerular endothelial permeability and kidney damage through antioxidant, anti-inflammatory, and KLF4-dependent mechanisms, offering potential therapeutic benefits for hypertension-related renal damage.</p></div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 7","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144550857","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Functionalized Zinc Oxide Nanoparticles Conjugated With Artemisinin Against Luperox-Induced Oxidative Stress and Their Impact on Antioxidant Defense Mechanism","authors":"Kadhirmathiyan Velumani,&nbsp;Ashley George Thomas,&nbsp;Mohammed Rafi Shaik,&nbsp;Shaik Althaf Hussain,&nbsp;Baji Shaik,&nbsp;Ajay Guru,&nbsp;Praveen Kumar Issac","doi":"10.1002/jbt.70380","DOIUrl":"https://doi.org/10.1002/jbt.70380","url":null,"abstract":"<div>\u0000 \u0000 <p>Reactive oxygen species (ROS) are the by-products of energy metabolism, which play various key roles in the body's metabolism. However, excessive ROS production may contribute to several diseases. Reports suggest that the functional properties of the nanoparticles can be altered by conjugating a plant's secondary metabolite. Artemisinin, extracted from <i>Artemisia annua</i>, was reported to have various therapeutic properties. We aim to synthesise artemisinin-conjugated zinc oxide nanoparticles (ART-ZnO NPs) and evaluate their antioxidant properties. In vitro studies showed that ART-ZnO NPs have the ability to scavenge free radicals effectively. The zebrafish developmental toxicity studies indicated that ART-ZnO NPs can protect the zebrafish larvae exposed to Luperox-induced oxidative stress from developmental and cognitive impairment. Further enzymatic analysis revealed that the ART-ZnO NPs upregulated the Antioxidant enzymes and downregulated the oxidative stress markers like lipid peroxidation and nitric oxide production. Additionally, they improved acetylcholinesterase enzyme activity, crucial for neuronal function, in stressed larvae. The fluorescence microscopy investigation showed ART-ZnO NPs also regulated the ROS and ROS-induced cell death in the zebrafish larvae exposed to Luperox-induced oxidative stress. Notably, ART-ZnO NPs increased the expression of both primary and secondary antioxidant enzymes and protected the larvae from oxidative stress-induced cell damage. Our findings strongly support the potential therapeutic properties of ART-ZnO NPs against oxidative stress. Further research is warranted to explore their applications in treating related conditions.</p></div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 7","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144515065","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Taurine and Neuroprotection: A Potential Shield Against Methylglyoxal-Induced Toxicity in SH-SY5Y Cells","authors":"Norah A. Althobaiti,&nbsp;Ifat Alsharif,&nbsp;Reem Hasaballah Alhasani,&nbsp;Aishah E. Albalawi,&nbsp;Mohammad Y. Alshahrani,&nbsp;Amany I. Almars,&nbsp;Ammar A. Basabrain,&nbsp;Mohammad H. Alhashmi,&nbsp;Zahrah R. Alrayes,&nbsp;Hailah M. Almohaimeed,&nbsp;Mona H. Soliman","doi":"10.1002/jbt.70343","DOIUrl":"https://doi.org/10.1002/jbt.70343","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 <p>Methylglyoxal (MG) is thought to have harmful effects on Alzheimer's disease (AD). On the other hand, taurine demonstrates promising potential for treating AD. Therefore, we examined the neuroprotective properties of taurine against MG in the SH-SY5Y cells. We used the MTT assay to evaluate the effects of taurine (0.5, 1, and 1.5 mg/mL) and MG (1200 and 2400 μM) on SH-SY5Y cell viability. We measured the expression of interleukin (IL)-6, IL-17, and IL-1β in the target cell line after treatment with MG and taurine. Following the treatment of SH-SY5Y cells with MG and taurine, we evaluated the expression levels of microRNA (miRNA)-101a, miRNA-137, miRNA-222, and miRNA-29c genes using real-time PCR. Furthermore, the Neurogenesis Plus RT² Profiler PCR array was utilized to identify the expression of genes associated with neurogenesis. The survival results indicated that increasing taurine concentrations reduces the toxicity of MG in SH-SY5Y cells. Treatment of SH-SY5Y cells with taurine + MG decreased the expression levels of IL-6, IL-17, and IL-1β compared to those treated with MG (<i>p </i>&lt; 0.05). Treatment with taurine led to increased expression of miRNA-101a, miRNA-137, miRNA-222, and miRNA-29c, with the highest levels observed at a concentration of 1 mg/mL (<i>p </i>&lt; 0.001). The results showed that when SH-SY5Y cells are exposed to MG (2400 μM) + taurine (1.5 mg/mL), genes SHH, BMP2, ERBB2, NEUROG2, BDNF, POU3F3, PARD3, PAX3, NR2E3, NRP2, CXCL1, and EGF had a significant increase (<i>p </i>&lt; 0.005). Taurine protects SH-SY5Y cells from MG-induced toxicity by enhancing cell viability, reducing inflammation, upregulating genes associated with neurogenesis, and upregulating specific miRNAs. This suggests taurine's potential as a therapeutic agent for conditions like AD. However, further in vivo studies and clinical trials are necessary to validate the therapeutic potential of taurine for AD.</p>\u0000 </section>\u0000 </div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 7","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144515134","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Design, Synthesis, Antimicrobial Evaluation, and In Silico Insights of Novel Thiazole-Based Benzylidene Thiazolidinones as Gyrase Inhibitors","authors":"Saad Alqarni,&nbsp;Magdi E. A. Zaki,&nbsp;Awatif H. Alruwaili,&nbsp;Mohamed El-Naggar,&nbsp;Ahmed Alafnan,&nbsp;Khaled Almansour,&nbsp;Bader Huwaimel,&nbsp;Amr S. Abouzied,&nbsp;Sobhi M. Gomha","doi":"10.1002/jbt.70367","DOIUrl":"https://doi.org/10.1002/jbt.70367","url":null,"abstract":"<div>\u0000 \u0000 <p>This study reports the design, synthesis, and antimicrobial evaluation of novel thiazole-based benzylidene thiazolidinones. Starting from 4-thiazolidinone intermediates (<b>3a</b> and <b>3b</b>), benzylidene derivatives (<b>5a-l, 7a,b</b>) and bis-derivatives (<b>9a,b</b>) were synthesized via condensation with aromatic aldehydes. In vitro antimicrobial screening against Gram-positive and Gram-negative bacteria, yeast, and fungi showed several compounds—especially <b>5 f</b> and <b>5 h</b>—exhibited significant activity comparable to gentamicin and fluconazole. Molecular docking against the <i>Staphylococcus aureus</i> gyrase-DNA complex further supported the experimental results, revealing strong binding affinities for select compounds, particularly <b>9b</b>. These findings suggest the synthesized thiazolidinones are promising candidates for developing new antimicrobial agents targeting resistant pathogens.</p></div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 7","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144515114","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SIRT1 Mediated by Baicalein and GFI1 Promotes Osteogenic Differentiation and Ameliorates Osteoporosis by Inhibiting Ferroptosis in Bone Marrow Mesenchymal Stem Cells","authors":"Liwei Bai,&nbsp;Tengfei Wang,&nbsp;Junsheng Zheng,&nbsp;Chaohui Bian,&nbsp;Yang Zhang,&nbsp;Yashi Fan","doi":"10.1002/jbt.70368","DOIUrl":"https://doi.org/10.1002/jbt.70368","url":null,"abstract":"<div>\u0000 \u0000 <p>Osteogenic differentiation (OD) of human bone marrow mesenchymal stem cells (hBMSCs) plays a vital role in bone formation, and its impairment contributes to osteoporosis, particularly estrogen-deficient osteoporosis (EDO). Baicalein (BN) and silent information regulator of transcription 1 (SIRT1) have been implicated in bone metabolism; however, the upstream regulatory mechanisms of SIRT1 and the potential synergistic effect of BN with the transcription factor growth factor independent 1 (GFI1) remain unclear. In this study, target genes were identified via SwissTargetPrediction and GeneCards databases, and protein-protein interaction (PPI) networks were constructed with Cytoscape software. The mRNA and protein expression levels were analyzed by RT-qPCR and Western blotting. The Alkaline phosphatase (ALP) Assay Kit was employed to analyze ALP activity in osteogenically differentiated hBMSCs. Alizarin red S (ARS) staining was utilized to assess cell calcification. Apoptosis was determined by flow cytometry. Kits were used to test changes in ferroptosis-related indicators such as malondialdehyde (MDA), glutathione (GSH), reactive oxygen species (ROS) and Fe²⁺ content. Cell viability was determined by the CCK-8 assay. The binding of GFI1 to the SIRT1 promoter was confirmed by dual-luciferase reporter and chromatin immunoprecipitation (ChIP) assays. A rat osteoporosis model was established for in vivo validation. Bioinformatics analysis identified SIRT1 as a common target of BN, ferroptosis, and EDO. SIRT1 expression was significantly decreased in osteoporosis patients’ peripheral blood but upregulated duringOD, paralleling increased GFI1 expression. ChIP assays confirmed GFI1's direct binding to the SIRT1 promoter, activating its transcription. BN treatment enhanced SIRT1 protein level. BN and GFI1 synergistically regulated SIRT1 at protein and transcriptional levels, respectively, promoting OD and inhibiting apoptosis and ferroptosis in hBMSCs. In vivo, BN facilitated OD in osteoporosis rats. These findings revealed a novel dual-level regulatory mechanism of SIRT1 by BN and GFI1, providing new insights into osteoporostic pathogenesis and suggesting potential therapeutic targets.</p></div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 7","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144520198","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}