Biochemical pharmacology最新文献

{"title":"Abrogation of PDE7A ameliorates alveolar epithelial EMT-Driven pulmonary fibrosis","authors":"Jianqiang Guo ,&nbsp;Jiawei Zhou ,&nbsp;Anqi Cheng ,&nbsp;Weinan Hu ,&nbsp;Tianxiang Qi ,&nbsp;Dahai Zhao ,&nbsp;Ying Bai ,&nbsp;Dong Hu ,&nbsp;Jing Wu","doi":"10.1016/j.bcp.2026.117785","DOIUrl":"10.1016/j.bcp.2026.117785","url":null,"abstract":"<div><div>Epithelial-mesenchymal transition (EMT) is a key driver of idiopathic pulmonary fibrosis (IPF), yet therapies specifically targeting epithelial cells remain limited. The role of phosphodiesterase 7A (PDE7A) in IPF and its mechanism in regulating EMT are still largely unknown. This study aims to investigate the anti-fibrotic effect of BRL-50481, focusing on its target PDE7A and the associated molecular mechanism in regulating epithelial cell fibrosis and EMT. BRL-50481 was identified as a top candidate compound targeting pathogenic alveolar epithelial cells through bioinformatic screening. Its efficacy was evaluated in both a bleomycin-induced murine pulmonary fibrosis model and a TGF-β-induced A549 cell model. Drug-target interaction was characterized using molecular docking, cellular thermal shift assay (CETSA), and site-directed mutagenesis. Downstream signaling pathways were predicted via the TRRUST database and experimentally validated. PDE7A was found to be highly expressed in alveolar epithelial cells of IPF patients and mice. BRL-50481 directly bound to the ILE323 residue of PDE7A, specifically inhibiting JAK2/STAT3 signaling pathway activation. This inhibition suppressed EMT, inflammatory factor release, and collagen deposition, ultimately alleviating pulmonary fibrosis in both in vivo and in vitro models. PDE7A acts as a key upstream regulator driving JAK2/STAT3 signaling activation and the EMT process in alveolar epithelial cells. BRL-50481 exerts anti-fibrotic effects by precisely targeting this mechanism, providing novel insights into IPF pathogenesis and establishing a theoretical foundation for developing innovative therapies targeting PDE7A.</div></div>","PeriodicalId":8806,"journal":{"name":"Biochemical pharmacology","volume":"247 ","pages":"Article 117785"},"PeriodicalIF":5.6,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146171740","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Kukoamine A attenuates allergic rhinitis via H1R antagonism: Dual suppression of inflammatory signaling and epithelial barrier disruption","authors":"Panpan Lei ,&nbsp;Xiaoyu Ma ,&nbsp;Yuxiu Zhang ,&nbsp;Sifan Xie ,&nbsp;Shiling Hu ,&nbsp;Yuanji Wang ,&nbsp;Weina Ma","doi":"10.1016/j.bcp.2026.117792","DOIUrl":"10.1016/j.bcp.2026.117792","url":null,"abstract":"<div><div>Allergic rhinitis (AR) has emerged as a significant global health burden with steadily rising prevalence. As the histamine 1 receptor (H₁R) plays a central role in allergic responses, it remains a key therapeutic target for AR. In this study, we used the AlphaFold 3 platform to predict the H₁R structure and performed high-throughput molecular docking, identifying kukoamine A (KuA) as a potential ligand targeting H₁R with unique structural features. Through comprehensive cell membrane chromatography (CMC) characterization and thermal/enzymatic stabilization assays, we established that KuA specifically binds to transmembrane domain (TM) 3 and TM6 of H₁R, inducing ligand-binding pocket expansion and consequent receptor inactivation. Furthermore, KuA significantly inhibits the activity of phospholipase C (PLC) and calcium influx, thereby blocking the NF-κB/ERK signaling pathway and reducing the secretion of inflammatory factors including TNF-α, IL-8 and MCP-1. Notably, KuA also preserved epithelial barrier integrity by stabilizing F-actin cytoskeleton and upregulating Claudin-1 expression. In both acute allergy and AR mouse models, KuA effectively alleviated inflammatory responses and restored nasal epithelial integrity. In conclusion, our findings demonstrate that KuA is a novel H₁R antagonist with dual anti-inflammatory and barrier-protective effects, positioning it as a highly promising therapeutic candidate for AR.</div></div>","PeriodicalId":8806,"journal":{"name":"Biochemical pharmacology","volume":"247 ","pages":"Article 117792"},"PeriodicalIF":5.6,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146171752","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Why things get important: GPCRs in salience processing","authors":"Nina K. Blum,&nbsp;Rainer K. Reinscheid","doi":"10.1016/j.bcp.2026.117768","DOIUrl":"10.1016/j.bcp.2026.117768","url":null,"abstract":"<div><div>Perception and processing of salient sensory input is vital for every animal. While sensory systems continuously receive a vast amount of information, animal brains are challenged to distinguish between relevant, i.e. salient, and neutral or unnecessary content. Stimulus salience can depend on intensity but also motivational and attentional states. Perception of salient information affects both immediate response behaviors and memory formation, which are both critical for survival. Conversely, aberrant salience processing may contribute to disorders such as schizophrenia or drug addiction. Research in recent decades has described several G protein-coupled receptor (GPCR) systems as important regulators of salience processing in the brain. They include receptors activated by monoamines, neuropeptides and lipid molecules. Although salience attribution is a critical brain function, a comprehensive survey of involved GPCRs and their endogenous transmitters has, to our knowledge, not been compiled. This review aims to close this gap by providing an overview of GPCRs involved in salience processing.</div></div>","PeriodicalId":8806,"journal":{"name":"Biochemical pharmacology","volume":"247 ","pages":"Article 117768"},"PeriodicalIF":5.6,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146117568","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Obacunone mitigates cisplatin-induced ototoxicity by activating CRHBP-mediated autophagy","authors":"Shaoqin Cen ,&nbsp;Zhenxing Hou ,&nbsp;Yuan Zhang ,&nbsp;Nan Wang ,&nbsp;Zihe Zhao ,&nbsp;Ao Li ,&nbsp;Guoqiang Wan ,&nbsp;Tianhong Zhang ,&nbsp;Xia Gao","doi":"10.1016/j.bcp.2026.117759","DOIUrl":"10.1016/j.bcp.2026.117759","url":null,"abstract":"<div><div>Cisplatin, a widely used antitumor agent, is limited in clinical application due to its ototoxicity. This study investigates the protective effects of obacunone, an active compound from Phellodendron bark, against cisplatin-induced hearing loss. Obacunone significantly improved the survival of cisplatin-treated House Ear Institute-Organ of Corti 1 (HEI-OC1) cells, preserved the cochlear explant, and enhanced auditory function in mice upon cisplatin treatment. Mechanistically, obacunone inhibited cisplatin-induced apoptosis by activating autophagy. Transcriptome profiling revealed that the expression of corticotropin-releasing hormone-binding protein (CRHBP) was increased in the cisplatin and obacunone co-treated group compared to the cisplatin-only group. Overexpression of CRHBP significantly enhanced autophagy and inhibited apoptosis, mirroring the effects of obacunone. Our findings demonstrate that obacunone promotes autophagy by upregulating CRHBP, thereby reducing cisplatin-induced hair cell apoptosis. This study provides a novel therapeutic strategy using the natural product obacunone for preventing cisplatin-induced hearing loss and highlights the potential of CRHBP as a target for otoprotective interventions.</div></div>","PeriodicalId":8806,"journal":{"name":"Biochemical pharmacology","volume":"247 ","pages":"Article 117759"},"PeriodicalIF":5.6,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146083922","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Icaritin enhances the antitumor efficacy of irinotecan by dual-targeting carboxylesterase 2 and p53 in vitro and in vivo","authors":"Jiahui Zhang ,&nbsp;Yaojun Wang ,&nbsp;Chunlai Yin ,&nbsp;Xiangyu Shi ,&nbsp;Zujia Chen ,&nbsp;Yingying Wang ,&nbsp;Yueyue Li ,&nbsp;Changyuan Wang ,&nbsp;Jie Li ,&nbsp;Jingjing Wu ,&nbsp;Yongshun Zhao","doi":"10.1016/j.bcp.2026.117777","DOIUrl":"10.1016/j.bcp.2026.117777","url":null,"abstract":"<div><div>Carboxylesterase 2 (CES2), a member of the serine hydrolase superfamily, plays a crucial role in catalyzing the hydrolysis of numerous endogenous and exogenous compounds containing ester bonds. The commonly used clinical drug irinotecan (CPT-11) exerts its anti-tumor effect by being hydrolyzed by CES2 to generate SN-38. Epimedium, a widely used traditional Chinese herb with multiple pharmacological properties, has not yet been characterized for its effects on CES2. Our study systematically evaluated the three principal bioactive components of Epimedium for their effects on CES2 activity, revealing that icaritin significantly activated this enzyme. <em>In vitro</em>, Western blot and RT-PCR assays demonstrated that icaritin significantly upregulated CES2 expression at both mRNA and protein levels. Furthermore, icaritin further enhanced CES2 expression by activating the PXR pathway and increased the protein level of P53. Molecular docking simulations demonstrated that the interation energy between CES2 and icaritin was significantly higher than that with cisplatin (a reported CES2 activator), which might suggest that CES2 has a higher affinity for icaritin than cisplatin. <em>In vivo</em> studies confirmed that icaritin increased the hydrolytic activity and protein expression of Ces in mouse liver and intestinal tissues with a concentration-dependent manner. In conclusion, icaritin can enhance the hydrolysis of irinotecan in vitro and in vivo, and this enhancement is related to the activation of CES2 and the increase of CES2 gene and protein expression. These findings have important clinical significance for reducing chemotherapy drug resistance in cancer patients.</div><div>Abbreviations: CES2, Carboxylesterase 2; CRC, Colorectal cancer; CPT-11, Irinotecan; CYP3A, Cytochrome P450 3A; NR, Nuclear receptor; P53, Tumor protein p53; PPAR-α, Peroxisome proliferator-activated receptor α; PXR, Pregnane X receptor; SN-38, 7-Ethyl-10-hydroxycamptothecin; UGT1A1, UDP-glucuronosyltransferase 1A1.</div></div>","PeriodicalId":8806,"journal":{"name":"Biochemical pharmacology","volume":"247 ","pages":"Article 117777"},"PeriodicalIF":5.6,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146137154","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"U07, a novel oridonin derivative, targets polo-like kinase 4 (PLK4) to induce ferroptosis in gastric cancer cells","authors":"Yingpeng Huang ,&nbsp;Yujie Lin ,&nbsp;Qishuo Zhou ,&nbsp;Yingqi Liang ,&nbsp;Mingdong Lu ,&nbsp;Fang Wu ,&nbsp;Qiantong Dong ,&nbsp;Jun Cheng","doi":"10.1016/j.bcp.2026.117774","DOIUrl":"10.1016/j.bcp.2026.117774","url":null,"abstract":"<div><div>This study aimed to systematically investigate the inhibitory effect and potential molecular mechanism of oridonin derivative U07 on gastric cancer cells. By combining in vitro cell experiments and in vivo animal experiments, techniques including Cell Counting Kit-8 (CCK-8) assay, colony formation assay, Annexin V-FITC/Propidium Iodide (Annexin V/PI) double-staining flow cytometry, Western blot, wound healing assay, Transwell invasion assay, fluorescence staining, surface plasmon resonance (SPR), isothermal titration calorimetry (ITC), and molecular docking were used to analyze the impact of U07 on the biological behavior of gastric cancer cells and related molecular pathways. The results showed that U07 exhibited concentration-dependent cytotoxicity against HGC-27 and MKN-45 gastric cancer cells (with IC₅₀ values of 2.5 μM and 2.6 μM, respectively). It could inhibit cell proliferation and induce apoptosis by activating the caspase-3 pathway, while significantly reducing cell migration and invasion abilities. U07 concentration-dependently increased the levels of reactive oxygen species (ROS) and lipid peroxidation, decreased glutathione (GSH) content, and increased malondialdehyde (MDA) content, thereby triggering ferroptosis; this effect could be blocked by the ferroptosis inhibitor Fer-1. Molecular studies confirmed that U07 could specifically bind to PLK4 kinase (KD = 6.2 μM detected by SPR, Kd = 0.65 μM detected by ITC) and inhibit its activity. PLK4 negatively regulates frroptosis pathway by directly binding to and transcriptionally activating Glutathione Peroxidase 4 (GPX4) / ferritin heavy chain 1 (FTH1). By downregulating PLK4, U07 further reduced the expression of ferroptosis marker proteins GPX4 and FTH1, and promoted lipid peroxidation and ROS production; however, overexpression of PLK4 could reverse these effects. In vivo experiments demonstrated that U07 could inhibit tumor growth in a dose-dependent manner, with the high-dose group (6 mg) showing an anti-tumor effect comparable to that of cisplatin, and it could downregulate the expression of PLK4 and GPX4 in tumor tissues. In conclusion, the oridonin derivative U07 exerts anti-gastric cancer effects by inhibiting cell proliferation, inducing apoptosis, and mediating ferroptosis via PLK4, providing a new candidate drug and therapeutic target for gastric cancer treatment.</div></div>","PeriodicalId":8806,"journal":{"name":"Biochemical pharmacology","volume":"247 ","pages":"Article 117774"},"PeriodicalIF":5.6,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146140925","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Eurycomanol alleviates hyperuricemia-induced cortisol disorders by upregulating SRD5A1 via IKKβ-IκBα-NF-κB-DNMT pathway","authors":"Jujie Pan ,&nbsp;Ruixia Bao ,&nbsp;Qian Chen ,&nbsp;Yuzheng Wu ,&nbsp;Beibei Chen ,&nbsp;Zicheng Zhu ,&nbsp;Jing Xie ,&nbsp;Yi Zhang ,&nbsp;Tao Wang ,&nbsp;Dan Wang","doi":"10.1016/j.bcp.2026.117787","DOIUrl":"10.1016/j.bcp.2026.117787","url":null,"abstract":"<div><div>Hyperuricemia (HUA) is a chronic metabolic disease which has been previously observed to be associated with cortisol metabolism disorders (pseudohypoadrenalism). In this study, we aimed to investigate the efficacy as well as mechanism of <em>Eurycoma longifolia</em> Jack (TkA) on alleviating cortisol metabolism. Oral administration of TkA significantly decreased serum uric acid levels and urinary cortisol in HUA mice. TkA improved HPA axis function and upregulated the levels of adrenal <em>Hsd3b2</em>, <em>Cyp21a1</em> and <em>Cyp11b1</em>. In the liver, TkA upregulated the expression of <em>Srd5a1</em> and <em>Akr1c4</em>, promoting the conversion from cortisol to 5α-tetrahydrocortisol (<em>P</em> &lt; 0.001). TNFα was found to be the principal driver of reduced SRD5A1. By activating NF-κB pathway, recruited DNA methyltransferase (DNMT) binding with the CpG islands increased methylation level of <em>Srd5a1</em>. Our findings highlight that eurycomanol significantly inhibited the activation of IKKβ/IκBα/NF-κB/DNMT pathway as well as up-regulated hepatic SRD5A1, thereby restoring the systemic cortisol metabolic homeostasis under HUA.</div></div>","PeriodicalId":8806,"journal":{"name":"Biochemical pharmacology","volume":"247 ","pages":"Article 117787"},"PeriodicalIF":5.6,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146163942","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Treatment with anti-Hsp90 antibody mitigates fibronectin-related cardiac fibrosis induced by pressure overload in mice","authors":"Tetsuro Marunouchi,&nbsp;Takuma Murakami,&nbsp;Kano Yamaguchi,&nbsp;Kotone Hiraga,&nbsp;Haruka Ban,&nbsp;Kouichi Tanonaka","doi":"10.1016/j.bcp.2026.117780","DOIUrl":"10.1016/j.bcp.2026.117780","url":null,"abstract":"<div><div>Heart failure is a chronic condition with a poor prognosis, and the development of new treatments is an urgent necessity. Extracellular heat shock protein 90 (eHsp90) has been observed to increase in heart failure. However, the pathophysiological role of extracellular Hsp90 (eHsp90) in heart failure development remains unclear. Thus, this study aimed to examine the effects of the anti-Hsp90 antibody 1G6-D7, an eHsp90 inhibitor, on cardiac fibrosis induced by pressure overload. Eight-week-old male C57Bl/6N mice underwent transverse aortic constriction (TAC). Beginning 2 <!--> <!-->weeks after surgery, the anti-Hsp90 antibody or normal IgG was administered intravenously every 2 weeks. Mice treated with normal IgG developed chronic heart failure with severe myocardial fibrosis 8 weeks after TAC. By contrast, administration of the anti-Hsp90 antibody to the TAC mice partially attenuated myocardial fibrosis and improved cardiac function. The fibronectin level in the myocardial tissue and the interaction between Hsp90 and fibronectin increased in the TAC mice treated with normal IgG. Conversely, these pathophysiological changes were mitigated in the TAC mice treated with the anti-Hsp90 antibody. The results of this study suggest that eHsp90 contributes to cardiac fibrosis by mediating fibronectin in the extracellular space. Furthermore, treatment with the anti-Hsp90 antibody attenuated cardiac fibrosis, which is associated with decreased fibronectin levels. The results of this study indicate eHsp90 as a novel extracellular target molecule for treating heart failure. In addition, our findings also suggested that anti-Hsp90 antibody hold considerable promise as potential pharmaceutical agents for the treatment of heart failure by targeting eHsp90.</div></div>","PeriodicalId":8806,"journal":{"name":"Biochemical pharmacology","volume":"247 ","pages":"Article 117780"},"PeriodicalIF":5.6,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146148954","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Oxidative stress in metabolic dysfunction-associated steatohepatitis: Mechanisms and emerging therapeutic strategies","authors":"Yidan Chen,&nbsp;Hui Yu,&nbsp;Xinyu Kai,&nbsp;Runting Yin,&nbsp;Zhen Ouyang,&nbsp;Yuan Wei,&nbsp;Cai Zhang","doi":"10.1016/j.bcp.2026.117702","DOIUrl":"10.1016/j.bcp.2026.117702","url":null,"abstract":"<div><div>Metabolic dysfunction-associated steatotic liver disease and its progressive form, metabolic dysfunction-associated steatohepatitis (MASH), affect a substantial proportion of the global population and have emerged as a major disease burden. If left untreated, MASH can progress to cirrhosis and hepatocellular carcinoma. However, effective pharmacological therapies for MASH remain limited. Accumulating evidence indicates that oxidative stress plays an important role in MASH pathogenesis by coordinating inflammatory responses and contributing to hepatocyte injury. Although previous studies have emphasized the importance of oxidative stress, a panoramic view of how oxidative stress emerges during the onset of MASH and sustains a vicious cycle of progression is still lacking. This review systematically discusses the mechanisms underlying oxidative stress-driven MASH progression, highlighting its interactions with inflammation, hepatocyte apoptosis, necroptosis, emerging ferroptosis, and mitochondria-associated membranes. Furthermore, we summarize the recent advances in investigational drugs targeting oxidative stress, encompassing key druggable targets as well as representative synthetic compounds, natural products, and biotechnology drugs. Collectively, this review aims to deepen the mechanistic understanding of oxidative stress in MASH and to provide insights into potential therapeutic strategies.</div></div>","PeriodicalId":8806,"journal":{"name":"Biochemical pharmacology","volume":"246 ","pages":"Article 117702"},"PeriodicalIF":5.6,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145958597","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Extracellular vesicles are a double-edged sword in cardiac fibrosis: an epigenetic perspective","authors":"Peng Liu ,&nbsp;Zhen-Yu Liu ,&nbsp;Sui Mao ,&nbsp;Li-Chan Lin ,&nbsp;Ye Zhang ,&nbsp;Jian-Yuan Zhao ,&nbsp;Hui Tao","doi":"10.1016/j.bcp.2026.117743","DOIUrl":"10.1016/j.bcp.2026.117743","url":null,"abstract":"<div><div>Cardiac fibrosis is regarded as a central mechanism by which different cardiovascular diseases react to a range of pathophysiological stimuli. The key features of cardiac fibrosis include the activation of fibroblasts, abnormal cellular proliferation, excessive extracellular matrix deposition, and an altered distribution of matrix components. As research on cardiac fibrosis advances, it has become increasingly clear that extracellular signals play a crucial role in regulating its initiation and progression. Hence, extracellular vesicles serve as pivotal mediators in intercellular communication, facilitating the transmission of a multitude of epigenetic signals and the conveyance of specific gene expression regulatory factors, thereby exerting a modulating influence on the development of cardiac fibrosis. Extracellular vesicles exhibit a dual role in cardiac fibrosis progression, as they can either promote or inhibit the fibrotic process. This review thoroughly explores the epigenetic regulatory mechanisms of extracellular vesicles (EVs) in mediating the process of cardiac fibrosis, and analyzes potential therapeutic intervention strategies. The research results indicate that extracellular vesicles have significant potential for treating cardiac fibrosis through epigenetic regulation, providing an important theoretical basis for the treatment and clinical application of related diseases.</div></div>","PeriodicalId":8806,"journal":{"name":"Biochemical pharmacology","volume":"246 ","pages":"Article 117743"},"PeriodicalIF":5.6,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146040177","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}