Chemical Biology & Drug Design最新文献

{"title":"Design and Synthesis of New Triazol Derivatives as Aromatase Enzyme Inhibitors","authors":"Abdullah Çelik,&nbsp;Hayrani Eren Bostancı,&nbsp;Şennur Görgülü,&nbsp;Mehmet Taha Yıldız,&nbsp;Ulviye Acar Çevik","doi":"10.1111/cbdd.70276","DOIUrl":"10.1111/cbdd.70276","url":null,"abstract":"<div>\u0000 \u0000 <p>In this study, novel triazole derivatives were designed and synthesized for potential breast cancer treatment. A series of 1,2,4-triazole compounds bearing a 2,4-difluorophenyl moiety (<b>3a–3r</b>) was obtained through a two-step organic synthesis process. The anticancer activities of the synthesized compounds were evaluated using the MTT assay in MCF-7 and L929 cell lines, and some derivatives (<b>3d, 3h, 3k, 3n</b>) exhibited selective cytotoxicity. The inhibitory effects of these compounds on the aromatase enzyme were determined and compared with those of letrozole. Molecular docking studies were performed to investigate the interactions of the most active compounds with the aromatase enzyme's active site, revealing binding energies and amino acid interactions. Finally, the ADME profiles of the lead compounds were assessed to analyze their pharmacokinetic properties. The findings suggest that the selected triazole derivatives may be promising novel candidates for aromatase inhibition in breast cancer therapy.</p>\u0000 </div>","PeriodicalId":143,"journal":{"name":"Chemical Biology & Drug Design","volume":"107 3","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147446406","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rutaecarpine Attenuates Ovalbumin-Induced Asthma in Mice by Regulating the NF-κB Pathway","authors":"Kongbo Chen,&nbsp;Junwei Chen","doi":"10.1111/cbdd.70275","DOIUrl":"10.1111/cbdd.70275","url":null,"abstract":"<div>\u0000 \u0000 <p>Pediatric asthma is a common chronic condition with several pathological features, including airway inflammation, remodeling, and oxidative stress. Rutaecarpine (RUT), a bioactive alkaloid, exhibits therapeutic efficacy against various allergic diseases. However, its roles in asthma and the underlying molecular mechanisms remain elusive. In this study, we established an ovalbumin (OVA)-induced mouse model of asthma. The results showed that compared with the OVA-challenged group, treatment with RUT (10 and 20 mg/kg) reduced lung tissue inflammatory scores by 37.5% and 50.0%, respectively. Additionally, RUT suppressed the production of interleukin (IL)-4, IL-5, and IL-13, and decreased the counts of total cells, eosinophils, macrophages, neutrophils, and lymphocytes in bronchoalveolar lavage fluid. Regarding airway remodeling, RUT downregulated the mRNA and protein expression of α-smooth muscle actin and type I collagen. Furthermore, periodic acid-Schiff staining showed that RUT ameliorated OVA-induced mucus hypersecretion. RUT treatment also exhibited a protective effect on OVA-induced oxidative damage in lung tissues. Mechanistically, RUT suppressed OVA-induced activation of the nuclear factor-kappa B (NF-κB) pathway. Collectively, RUT attenuated inflammation, airway remodeling, and oxidative stress in OVA-induced asthmatic mice by inhibiting the NF-κB pathway, highlighting its potential as an adjunct therapy for pediatric asthma and providing a theoretical basis for future clinical translation.</p>\u0000 </div>","PeriodicalId":143,"journal":{"name":"Chemical Biology & Drug Design","volume":"107 3","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147379795","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Berberine Ameliorates Pulmonary Fibrosis via Downregulating the TGFBR2-Mediated Signaling","authors":"Yichao Zhao,&nbsp;Qi Li,&nbsp;Huihui Zhu,&nbsp;Cheng Jiang,&nbsp;Min Chen,&nbsp;Xiaoling Ye,&nbsp;Shixuan Hou,&nbsp;Sihao Cui,&nbsp;Xinmei Huang,&nbsp;Mengshu Cao","doi":"10.1111/cbdd.70264","DOIUrl":"10.1111/cbdd.70264","url":null,"abstract":"<div>\u0000 \u0000 <p>Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive fibrosing interstitial lung disease without any effective treatment. Berberine (BBR), a botanical alkaloid, possesses extensive biological activities and has significant therapeutic value in various diseases. However, the effect and potential mechanisms of BBR on pulmonary fibrosis remain elusive. In vivo, BBR was administered by gavage following intratracheal instillation of bleomycin (BLM) in a mouse model from Day 1 to Day 20. In vitro, Human Lung Fibroblast (HLF) and A549 cell lines were used to explore the effects of BBR on transforming growth factor β1 (TGF-β1) treated cells. Both cell lines were transfected with a lentivirus carrying TGF-β receptor 2 (TGFBR2) knockdown genes, and the autophagy inhibitor chloroquine (CQ) and PI3K inhibitor LY294002 were employed to investigate the underlying effects of BBR on TGF-β signaling and autophagy in pulmonary fibrosis. BBR administration attenuates pulmonary inflammation and fibrosis of BLM-induced mice in vivo. Analogously, BBR treatment significantly alleviates matrix collagen deposition and reduces the expression of fibrotic markers in TGF-β1-treated human lung fibroblasts (HLF) and alveolar epithelial cell (A549) in vitro. Mechanistically, we found that BBR downregulates the expression of TGFBR2 and suppresses TGF-β/Smad2/3 signaling in vivo and in vitro. Furthermore, BBR inhibits the activation of the PI3K/AKT/mTOR pathway and autophagy, then downregulates the expression of pro-fibrotic genes. The effect of BBR on pulmonary fibrosis was further verified using both TGF-β1-treated HLF and A549 cells with the addition of the inhibitors of PI3K, LY294002, and autophagy, CQ in vitro, respectively. Our study suggests that BBR can inhibit pulmonary fibrosis by down-regulating the expression of TGFBR2, attenuating TGF-β/Smad2/3 signal, and activating autophagy through phosphorylation of PI3K/AKT/mTOR.</p>\u0000 </div>","PeriodicalId":143,"journal":{"name":"Chemical Biology & Drug Design","volume":"107 3","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147379786","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrative Experimental Paradigm of Oxadiazole–Schiff Base Hybrids: Pharmacophore-Driven Docking Simulations and DFT Insights Toward Antidiabetic Therapeutic Discovery","authors":"Aisha Bibi,&nbsp;Mostafa E. Salem,&nbsp;Shoaib Khan,&nbsp;Tayyiaba Iqbal,&nbsp;Wajid Rehman,&nbsp;Eman Alzahrani,&nbsp;Khasan Kayumov,&nbsp;Mohamed Abdel-Megid","doi":"10.1111/cbdd.70270","DOIUrl":"10.1111/cbdd.70270","url":null,"abstract":"<div>\u0000 \u0000 <p>Diabetes mellitus and gastrointestinal infections remain major global health concerns, contributing to high morbidity, mortality, and economic burden. To address these challenges, a series of oxadiazole-bearing imine scaffolds were designed and synthesized as dual α-glucosidase and urease inhibitors. Among them, compound 5 (IC₅₀ = 5.30 ± 0.20 μM for α-glucosidase; 8.60 ± 0.30 μM for urease) and compound 6 (IC₅₀ = 3.80 ± 0.60 μM; 5.20 ± 0.40 μM) exhibited the most potent inhibitory activity. The in vitro potential of these compounds was compared with the standard compounds urease (IC₅₀ = 12.20 ± 0.21 μM) and acarbose (IC₅₀ = 10.30 ± 1.10 μM). All compounds were synthesized and characterized using ¹H NMR, ¹³C NMR, and HREI-MS. In silico studies, including molecular docking, revealed strong binding interactions between the active molecules and target enzymes. Density Functional Theory (DFT) analysis provided insights into electronic characteristics such as HOMO–LUMO energy gaps and reactive molecular regions, while ADMET profiling confirmed favorable drug-likeness. Pharmacophore modeling of compound 6 highlighted critical hydrogen-bonding interactions, and molecular dynamics simulations further validated the stability and affinity of the protein–ligand complexes. Collectively, these findings suggest that the synthesized oxadiazole derivatives are promising dual inhibitors with potential therapeutic relevance in diabetes and gastrointestinal infections.</p>\u0000 </div>","PeriodicalId":143,"journal":{"name":"Chemical Biology & Drug Design","volume":"107 3","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147379861","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Design, Synthesis, and Evaluation of Bis-Chalcones and Bis-Flavones as Selective COX-2 Inhibitors","authors":"Rui Pereira,&nbsp;Marisa Freitas,&nbsp;Alberto N. Araújo,&nbsp;Vera L. M. Silva,&nbsp;Eduarda Fernandes","doi":"10.1111/cbdd.70268","DOIUrl":"10.1111/cbdd.70268","url":null,"abstract":"<p>Over the past two decades, the search for safe and effective COX-2 inhibitors has spurred extensive research on flavonoids. Within this context, synthetic flavonoid dimers have emerged as a promising subclass with potential anti-inflammatory activity. To investigate whether dimerization enhances their potency and selectivity, novel A-fused <i>bis</i>-chalcones and A-fused <i>bis</i>-flavones were synthesized and evaluated for their inhibitory activity against isolated human COX-1 and COX-2 enzymes, as well as their effects on prostaglandin E₂ production in whole human blood. Interestingly, the most active compound identified was a monomeric chalcone sharing the same substitution pattern as the top-performing <i>bis</i>-chalcone, suggesting that key structural features drive activity regardless of dimerization. While the dimeric nature of <i>bis</i>-chalcones did not enhance COX-2 inhibition or selectivity in this study, these results provide valuable insights into structure–activity relationships. Furthermore, all active compounds against the isolated enzyme showed reduced potency in whole blood, possibly due to plasma protein binding limiting bioavailability. This study highlights the importance of rational design for further development of dimeric flavonoids, in particular strategies aimed at optimizing bioavailability.</p>","PeriodicalId":143,"journal":{"name":"Chemical Biology & Drug Design","volume":"107 3","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12949472/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147319231","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of 5-Gene Prognostic Markers and Functional Verification of RRBP1 in 5-Fluorouracil Resistance of Colorectal Cancer by Multi-Omics Analysis and Experimental Verification","authors":"Hui Ge,&nbsp;Zheng Xiao,&nbsp;Peiming Zheng,&nbsp;Chongmei Zhou","doi":"10.1111/cbdd.70265","DOIUrl":"10.1111/cbdd.70265","url":null,"abstract":"<div>\u0000 \u0000 <p>Acquired resistance to 5-fluorouracil (5-FU) is a primary clinical challenge in colorectal cancer (CRC) treatment. Our study aimed to identify key factors predictive of 5-FU resistance and to elucidate their functional mechanisms by combining multi-omics analysis with experimental verification. The prognostic model was constructed based on the gene expression omnibus (GEO, GSE196900, GSE166555) and the cancer genome atlas (TCGA)-Colon Adenocarcinoma (COAD) datasets combined with regression analysis. Kaplan–Meier (K-M), receiver operating characteristic (ROC) curve, and nomogram were used to evaluate the predictive performance of the prognostic model. Gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) were used for functional enrichment analysis. Single-cell RNA sequencing (scRNA-seq, GSE166555) and qRT-PCR analysis were used to analyze the tumor microenvironment and gene expression. In cell experiments, CCK-8 assay measured IC₅₀ value. Glycolysis metabolism was evaluated by detecting glucose consumption, lactic acid production, extracellular acidification rate (ECAR), and oxygen consumption rate (OCR); cell stemness was evaluated by sphere formation assay. A 5-gene prognostic model was successfully constructed, which could effectively distinguish the high−/low-risk groups of CRC patients and was significantly correlated with overall survival. Ribosome binding protein 1 (RRBP1) is highly expressed in cancer tissues of non-responders to chemotherapy. It is also highly expressed in tumor epithelial cells, and its high expression is closely related to aneuploidy characteristics, up-regulation of oncogenes, and activation of pro-survival pathways. In vitro experiments confirmed that knockdown of RRBP1 significantly enhanced the sensitivity of CRC cells to 5-FU and inhibited cell proliferation. Mechanistically, RRBP1 knockdown effectively reversed the enhanced glycolysis activity and stem cell-like properties of 5-FU-resistant cells. This study established RRBP1 as a key CRC prognostic factor and 5-FU resistance driver, operating through the regulation of cell glycolysis and stemness. RRBP1 emerges as a new biomarker and therapeutic target for predicting the efficacy of 5-FU.</p>\u0000 </div>","PeriodicalId":143,"journal":{"name":"Chemical Biology & Drug Design","volume":"107 3","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147313405","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Old Drug, New Opportunity: Drug Repurposing in Cardiovascular Diseases","authors":"Xiuyi Ou,&nbsp;Sa Liu,&nbsp;Pengcheng Sun,&nbsp;Yuanying Yang,&nbsp;Yangchun Xie,&nbsp;Bikui Zhang,&nbsp;Yuanjian Li,&nbsp;Wenqun Li,&nbsp;Taoli Sun","doi":"10.1111/cbdd.70272","DOIUrl":"https://doi.org/10.1111/cbdd.70272","url":null,"abstract":"<div>\u0000 \u0000 <p>Cardiovascular disease (CVD) remains the major burden on global health. However, the development and approval of novel CVD therapeutics have declined, largely due to their protracted timelines and prohibitive costs. Drug repurposing has emerged as a promising strategy to overcome these limitations by leveraging data from approved drugs, thereby reducing both developmental costs and time-to-application. In this review, we systematically evaluate the repurposing potential of currently available drugs for CVD, elucidating their potential mechanisms, efficacy, and safety profiles. Furthermore, we discuss methodologies that facilitate the identification of promising repurposing candidates. These approaches may yield safer, more efficacious, and cost-effective alternatives for CVD, bridging the gap between clinical needs and drug development pipelines. We also address the translational and commercial barriers specific to CVD drug repurposing and propose that integrating precision medicine, artificial intelligence driven discovery, and collaborative frameworks represents a viable strategy to overcome these hurdles.</p>\u0000 </div>","PeriodicalId":143,"journal":{"name":"Chemical Biology & Drug Design","volume":"107 2","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147288454","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Anti-Proliferative and Apoptotic Evaluation of a Novel Synthesized Acridine Hybrid With Anticipated Synergistic Effect to Paclitaxel on Breast Cancer Cells","authors":"Esraa A. Aidy,&nbsp;Elshaymaa I. Elmongy,&nbsp;Abdullah A. S. Ahmed,&nbsp;Ibrahim El Tantawy El Sayed,&nbsp;Hanan Ali Henidi,&nbsp;Saad M. EL-Gendy,&nbsp;Yasmin S. EL-Gendy,&nbsp;Ahmed Ibrahim El-Tantawy,&nbsp;Heba Effat","doi":"10.1111/cbdd.70269","DOIUrl":"10.1111/cbdd.70269","url":null,"abstract":"<div>\u0000 \u0000 <p>This work describes the design, synthesis, and anticancer evaluation of a new acridine hybrid (ACNP). ACNP showed cytotoxic effect with IC₅₀ values of 4.3 and 10 μg/mL against MCF-7 and MDA-MB 231; respectively, versus CC₅₀ value of 439.72 μg/mL of normal lung fibroblast cells (WI-38 cells) with high selectivity index (SI) of 102.2 and 43.9 for MCF-7 and MDA-MB 231 of cancer cells respectively. ACNP showed a cytotoxic synergetic effect when combined with paclitaxel in MDA-MB 231 and MCF-7 cell lines. A significant down regulation of PI3K, mTOR and AKT was demonstrated in cells treated with paclitaxel or ACNP as single therapy with minimal expression in cells treated with combination of both. ACNP treated cells recorded an increase in protein expression level of Caspase-3, Caspase-9 while Ki67 showed a declined expression in MDA-MB 231 and MCF-7 cell lines. Molecular docking investigation was performed on PI3K and Caspase-3 to predict the possible binding modes of the acridine tricyclic skeleton with the molecular targets. The ADME study revealed that ACNP has high GI absorption and blood brain barrier although oral bioavailability was poor. These results suggested that ACNP maybe a promising candidate for further preclinical development.</p>\u0000 </div>","PeriodicalId":143,"journal":{"name":"Chemical Biology & Drug Design","volume":"107 2","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147286653","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Epigallocatechin Gallate, Resveratrol, and Triptolide Are Candidate Natural Drugs Which Target Huh Proteins in Atherosclerosis Pathogenesis","authors":"Xiaoshan Zhu,&nbsp;Yuanyuan Nie,&nbsp;Hongshen Zhang,&nbsp;Yue Zhang,&nbsp;Hanyun Zhou","doi":"10.1111/cbdd.70262","DOIUrl":"10.1111/cbdd.70262","url":null,"abstract":"<div>\u0000 \u0000 <p>The aim of this study was to screen and validate hub genes involved in atherosclerosis (AS) pathogenesis and explore potential natural drugs. The differentially expressed genes (DEGs) associated with AS were collected based on microarray data. Functional enrichment analysis was performed using the “clusterProfiler” R package. The protein–protein interaction (PPI) network was constructed using the STRING database, and the CytoHubba plug-in in the Cytoscape 3.9.0 software was used to identify hub target genes. The diagnostic efficacy of the hub gene was evaluated using receiver operating characteristic curve. Molecular docking was used to screen out naturally small molecules with potential therapeutic effects, and their binding relationship was further validated by molecular dynamics simulation and cellular thermal shift assay. Human umbilical vein endothelial cells (HUVECs) were induced by oxidizing low-density lipoprotein (ox-LDL) in vitro. After treatment, cell counting kit-8 assay and lactate dehydrogenase (LDH) release assay were used to evaluate cell viability. Apoptosis was analyzed by flow cytometry. The levels of reactive oxygen species (ROS), superoxide dismutase (SOD), and malondialdehyde (MDA) were detected to evaluate the oxidative stress. The levels of tumor necrosis factor (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β) were detected by enzyme-linked immunosorbent assay (ELISA). Reverse transcription quantitative polymerase chain reaction (RT-qPCR) and Western blot were used to detect the expression change of hub target genes. In this study, TNF, toll-like receptor 4 (TLR4), and signal transducer and activator of transcription 1 (STAT1) were identified as the hub targets in AS pathogenesis. They had high specificity and sensitivity for the diagnosis of AS. Importantly, epigallocatechin gallate (EGCG), resveratrol (RSV), and triptolide (TP) showed good binding affinities with these hub targets. EGCG, RSV, or TP treatment could reduce ox-LDL-induced HUVECs injury by enhancing cell viability, reducing LDH release, inhibiting apoptosis, oxidative stress, and inflammatory response. In addition, EGCG, RSV, or TP therapy also reduced mRNA and protein expression levels of TNF, TLR4, and STAT1 in HUVECs. In summary, EGCG, RSV, and TP may be naturally active small molecules for AS treatment. The mechanism may be associated with the regulation of endothelial cell inflammation and injury. The novelty of the present work was that it systematically identified TNF, TLR4, and STAT1 as key hub targets in AS pathogenesis through integrated bioinformatics analysis and experimental validation, and further demonstrated that EGCG, RSV, and TP may exert therapeutic effects on AS.</p>\u0000 </div>","PeriodicalId":143,"journal":{"name":"Chemical Biology & Drug Design","volume":"107 2","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147277806","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Quercetin Suppresses Inflammation and Extracellular Matrix Degradation in Knee Osteoarthritis by Inhibiting E2F2 to Modulate SFRP5/Wnt5a Signaling","authors":"Jinlong Yao,&nbsp;Juan Li,&nbsp;Yun Zhang,&nbsp;Pu Guo,&nbsp;Jianbo Li,&nbsp;Shaoqiu Sun","doi":"10.1111/cbdd.70241","DOIUrl":"10.1111/cbdd.70241","url":null,"abstract":"<div>\u0000 \u0000 <p>Quercetin (QUR) has been shown to ameliorate knee osteoarthritis (KOA), but its precise mechanism remains unclear. This study aimed to determine whether QUR regulates KOA by modulating E2F Transcription Factor 2 (E2F2) and elucidate the underlying mechanism. A rat anterior cruciate ligament model was established to simulate KOA. Molecular expression levels were evaluated using Reverse Transcription Quantitative Real-Time Polymerase Chain Reaction, Western blot, and immunohistochemistry. Cell viability and apoptosis were assessed using cell counting kit-8 assay and flow cytometry, respectively. E2F2 binding to secreted frizzled-related protein 5 (SFRP5) promoter was confirmed through chromatin immunoprecipitation and dual-luciferase reporter assays. Cartilage pathological damage was evaluated using hematoxylin and eosin and safranine-O/fast-green staining. QUR attenuated Interleukin-1beta-induced chondrocyte inflammation, extracellular matrix (ECM) degradation, and cartilage injury by downregulating E2F2 and inactivating the Wnt5a/Dishevelled 2 (Dvl2)/Jun N-terminal kinase (JNK) pathway. E2F2 bound the SFRP5 promoter and inhibited its transcription, whereas SFRP5 overexpression counteracted E2F2-mediated activation of the Wnt5a/Dvl2/JNK pathway. QUR suppresses chondrocyte inflammation and ECM degradation in KOA by downregulating E2F2 and modulating the SFRP5/Wnt5a/Dvl2/JNK pathway. These findings highlight the E2F2/SFRP5/Wnt5a axis as a promising therapeutic target for KOA and support the further development of quercetin as a potential treatment strategy.</p>\u0000 </div>","PeriodicalId":143,"journal":{"name":"Chemical Biology & Drug Design","volume":"107 2","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147286679","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}