Acta Pharmaceutica Sinica. B最新文献_第8页

Downregulation of ubiquitous microRNA-320 in hepatocytes triggers RFX1-mediated FGF1 suppression to accelerate MASH progression 肝细胞中普遍存在的microRNA-320下调可触发rfx1介导的FGF1抑制，从而加速MASH进展

IF 14.6 1区医学

Acta Pharmaceutica Sinica. B Pub Date : 2025-08-01 DOI: 10.1016/j.apsb.2025.06.007

Liu Yang , Wenjun Li , Yingfen Chen , Ru Ya , Shengying Qian , Li Liu , Yawen Hao , Qiuhong Zai , Peng Xiao , Seonghwan Hwang , Yong He

{"title":"Downregulation of ubiquitous microRNA-320 in hepatocytes triggers RFX1-mediated FGF1 suppression to accelerate MASH progression","authors":"Liu Yang , Wenjun Li , Yingfen Chen , Ru Ya , Shengying Qian , Li Liu , Yawen Hao , Qiuhong Zai , Peng Xiao , Seonghwan Hwang , Yong He","doi":"10.1016/j.apsb.2025.06.007","DOIUrl":"10.1016/j.apsb.2025.06.007","url":null,"abstract":"<div><div>Metabolic dysfunction-associated steatohepatitis (MASH), a severe type of metabolic dysfunction-associated steatotic liver disease (MASLD), is a leading etiology of end-stage liver disease worldwide, posing significant health and economic burdens. microRNA-320 (miR-320), a ubiquitously expressed and evolutionarily conserved miRNA, has been reported to regulate lipid metabolism; however, whether and how miR-320 affects MASH development remains unclear. By performing miR-320 <em>in situ</em> hybridization with RNAscope, we observed a notable downregulation of miR-320 in hepatocytes during MASH, correlating with disease severity. Most importantly, miR-320 downregulation in hepatocytes exacerbated MASH progression as demonstrated that hepatocyte-specific miR-320 deficient mice were more susceptible to high-fat, high-fructose, high-cholesterol diet (HFHC) or choline-deficient, amino acid-defined, high-fat diet (CDAHFD)-induced MASH compared with control littermates. Conversely, restoration of miR-320 in hepatocytes ameliorated MASH-related steatosis and fibrosis by injection of adeno-associated virus 8 (AAV8) carrying miR-320 in different types of diet-induced MASH models. Mechanistic studies revealed that miR-320 specifically regulated fibroblast growth factor 1 (FGF1) production in hepatocytes by inhibiting regulator factor X1 (RFX1) expression. Notably, knockdown of <em>Rfx1</em> in hepatocytes mitigated MASH by enhancing FGF1-mediated AMPK activation. Our findings underscore the therapeutic potential of hepatic miR-320 supplementation in MASH treatment by inhibiting RFX1-mediated FGF1 suppression.</div></div>","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":"15 8","pages":"Pages 4096-4114"},"PeriodicalIF":14.6,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144863818","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

Macrophage DGKζ-mediated phosphatidic acid remodeling aggravates acute liver failure 巨噬细胞dgkζ介导的磷脂酸重塑可加重急性肝衰竭

IF 14.6 1区医学

Acta Pharmaceutica Sinica. B Pub Date : 2025-08-01 DOI: 10.1016/j.apsb.2025.06.019

Yumeng Miao , Tzuchun Lin , Bianlin Wang , Junyu Xu , Chongxian Li , Zuopeng Li , Xinwen Zhang , Chendong Zhou , Tuerganaili Aji , Minjia Tan , Haji Akber Aisa , Jingya Li

{"title":"Macrophage DGKζ-mediated phosphatidic acid remodeling aggravates acute liver failure","authors":"Yumeng Miao , Tzuchun Lin , Bianlin Wang , Junyu Xu , Chongxian Li , Zuopeng Li , Xinwen Zhang , Chendong Zhou , Tuerganaili Aji , Minjia Tan , Haji Akber Aisa , Jingya Li","doi":"10.1016/j.apsb.2025.06.019","DOIUrl":"10.1016/j.apsb.2025.06.019","url":null,"abstract":"<div><div>Acute liver failure (ALF) is a life-threatening condition associated with macrophage-mediated inflammatory responses. Effective therapies and drugs are still lacking to date. Here, we reveal that a derivative of xanthohumol, CAM12203, alleviates lipopolysaccharide (LPS) + <span>d</span>-galactosamine (D-GalN)-induced ALF through limiting macrophage-mediated inflammation, with the most significant impact on interleukin-1<em>β</em> (IL-1<em>β</em>) transcription. Through biotin labeling-mediated pull-down and LC–MS/MS analysis, diacylglycerol kinase <em>ζ</em> (DGK<em>ζ</em>), a lipid-metabolizing kinase, is identified as the direct target of CAM12203. Mechanistically, DGK<em>ζ</em> is induced in macrophages upon inflammatory stimuli and is upregulated observed on clinical liver failure samples. Its product phosphatidic acid (PA) boosts phospholipase C (PLC)–inositol 1,4,5-trisphosphate (IP<sub>3</sub>)–Ca<sup>2+</sup> signaling and subsequent janus kinase 2 (JAK2)–signal transducer and activator of transcription 3 (STAT3) cascade, ultimately promoting IL-1<em>β</em> production and liver failure. DGK<em>ζ</em> knockdown/ablation or inhibition significantly impairs the DGK<em>ζ</em>–STAT3–IL-1<em>β</em> pathway along with ALF progression. Finally, CAM12203 is confirmed to be a new DGK<em>ζ</em> inhibitor and acts against inflammation in a DGK<em>ζ</em>-reliant manner. Taken together, CAM12203 inhibits IL-1<em>β</em> transcription in macrophages by binding to DGK<em>ζ</em> and blocking the DGK<em>ζ</em>–STAT3 axis, thereby exerting an ameliorative effect on ALF. These results not only highlight CAM12203 as a promising lead compound for ALF treatment, but also define DGK<em>ζ</em> as a novel therapeutic target.</div></div>","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":"15 8","pages":"Pages 4078-4095"},"PeriodicalIF":14.6,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144863810","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

Rapid discovery of drug-introduced multiple organ dysfunction via NIR-II fluorescent imaging 通过NIR-II荧光成像快速发现药物引入的多器官功能障碍

IF 14.6 1区医学

Acta Pharmaceutica Sinica. B Pub Date : 2025-08-01 DOI: 10.1016/j.apsb.2025.06.023

Pu Jiang , Ruihu Song , Yue Hu , Xin He , Zewei Zhang , Xuemei Wei , Zhiming Wang , De-an Guo , Hao Chen

{"title":"Rapid discovery of drug-introduced multiple organ dysfunction via NIR-II fluorescent imaging","authors":"Pu Jiang , Ruihu Song , Yue Hu , Xin He , Zewei Zhang , Xuemei Wei , Zhiming Wang , De-an Guo , Hao Chen","doi":"10.1016/j.apsb.2025.06.023","DOIUrl":"10.1016/j.apsb.2025.06.023","url":null,"abstract":"<div><div>The precise and rapid monitoring of multiple organ dysfunction is crucial in drug discovery. Traditional methods, such as pathological analysis, are often time-consuming and inefficient. Here, we developed a multiplexed near-infrared window two (NIR-II) fluorescent bioimaging method that allows for real-time, rapid, and quantitative assessment of multiple organ dysfunctions. Given that existing probes did not fully meet requirements, we synthesized a range of NIR-II hemicyanine dyes (HDs) with varying absorption and emission wavelengths. By modifying these dyes, we achieved high spatial and temporal resolution imaging of the liver, kidneys, stomach, and intestines. This method was further applied to investigate disorders induced by cisplatin, a drug known to cause gastric emptying issues along with liver and kidney injuries. By monitoring the metabolic rate of the dyes in these organs, we accurately quantified multi-organ dysfunction, which was also confirmed by gold-standard pathological analysis. Additionally, we evaluated the effects of five aristolochic acids (AAs) on multiple organ dysfunction. For the first time, we identified that AA-I and AA-II could cause gastric emptying disorders, which was further validated through transcriptomics analysis. Our study introduces a novel approach for the simultaneous monitoring of multi-organ dysfunction, which may significantly enhance the evaluation of drug side effects.</div></div>","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":"15 8","pages":"Pages 4285-4299"},"PeriodicalIF":14.6,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144863245","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

Engineered tumor specific AAV for IL-12 delivery in ovarian cancer immunotherapy 卵巢癌免疫治疗中IL-12传递的工程化肿瘤特异性AAV

IF 14.6 1区医学

Acta Pharmaceutica Sinica. B Pub Date : 2025-08-01 DOI: 10.1016/j.apsb.2025.05.033

Fan Tong , Hanmei Li , Huile Gao , Yuan Li

引用次数: 0

High-efficient discovering the potent anti-Notum agents from herbal medicines for combating glucocorticoid-induced osteoporosis 从中草药中高效发现抗糖皮质激素所致骨质疏松症的有效药物

IF 14.6 1区医学

Acta Pharmaceutica Sinica. B Pub Date : 2025-08-01 DOI: 10.1016/j.apsb.2025.06.004

Yuqing Song , Feng Zhang , Jia Guo , Yufan Fan , Hairong Zeng , Mengru Sun , Jun Qian , Shenglan Qi , Zihan Chen , Xudong Jin , Yunqing Song , Tian Tian , Zhi Qian , Yao Sun , Zhenhao Tian , Baoqing Yu , Guangbo Ge

{"title":"High-efficient discovering the potent anti-Notum agents from herbal medicines for combating glucocorticoid-induced osteoporosis","authors":"Yuqing Song , Feng Zhang , Jia Guo , Yufan Fan , Hairong Zeng , Mengru Sun , Jun Qian , Shenglan Qi , Zihan Chen , Xudong Jin , Yunqing Song , Tian Tian , Zhi Qian , Yao Sun , Zhenhao Tian , Baoqing Yu , Guangbo Ge","doi":"10.1016/j.apsb.2025.06.004","DOIUrl":"10.1016/j.apsb.2025.06.004","url":null,"abstract":"<div><div>Notum, a negative feedback regulator of the Wnt signaling, has emerged as a promising target for treating glucocorticoid-induced osteoporosis (GIOP). This study showcases an efficient strategy for discovering the anti-Notum constituents from herbal medicines (HMs) as novel anti-GIOP agents. Firstly, a rapid-responding near-infrared fluorogenic substrate for Notum was rationally engineered for high-throughput identifying the anti-Notum HMs. The results showed that Bu-Gu-Zhi (BGZ), a known anti-osteoporosis herb, potently inhibited Notum in a competitive-inhibition manner. To uncover the key anti-Notum constituents in BGZ, an efficient strategy was adapted <em>via</em> integrating biochemical, phytochemical, computational, and pharmacological assays. Among all identified BGZ constituents, three furanocoumarins were validated as strong Notum inhibitors, while 5-methoxypsoralen (5-MP) showed the most potent anti-Notum activity and favorable safety profiles. Mechanistically, 5-MP acted as a competitive inhibitor of Notum <em>via</em> creating strong hydrophobic interactions with Trp128 and Phe268 in the catalytic cavity of Notum. Cellular assays showed that 5-MP remarkably promoted osteoblast differentiation and activated Wnt signaling in dexamethasone (DXMS)-challenged MC3T3-E1 osteoblasts. In dexamethasone-induced osteoporotic mice, 5-MP strongly elevated bone mineral density (BMD) and improved cancellous and cortical bone thickness. Collectively, this study constructs a high-efficient platform for discovering key anti-Notum constituents from HMs, while 5-MP emerges as a promising anti-GIOP agent.</div></div>","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":"15 8","pages":"Pages 4174-4192"},"PeriodicalIF":14.6,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144863246","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

Improved prebiotic-based “shield” equipped probiotics for enhanced colon cancer therapy by polarizing M1 macrophages and regulating intestinal microbiota 改良的益生元“盾牌”装备益生菌通过极化M1巨噬细胞和调节肠道微生物群来增强结肠癌治疗

IF 14.6 1区医学

Acta Pharmaceutica Sinica. B Pub Date : 2025-08-01 DOI: 10.1016/j.apsb.2025.05.040

Yang Wang , Xiaomin Su , Yao Liu , Lina Hu , Lin Kang , Ce Xu , Zanya Sun , Chenyu Sun , Huishu Guo , Shun Shen

{"title":"Improved prebiotic-based “shield” equipped probiotics for enhanced colon cancer therapy by polarizing M1 macrophages and regulating intestinal microbiota","authors":"Yang Wang , Xiaomin Su , Yao Liu , Lina Hu , Lin Kang , Ce Xu , Zanya Sun , Chenyu Sun , Huishu Guo , Shun Shen","doi":"10.1016/j.apsb.2025.05.040","DOIUrl":"10.1016/j.apsb.2025.05.040","url":null,"abstract":"<div><div>Probiotics play a crucial role in colon cancer treatment by metabolizing prebiotics to generate short-chain fatty acids (SCFAs). Colon cancer patients are frequently propositioned to supplement with probiotics to enhance the conversion and utilization of prebiotics. Nevertheless, the delivery and colonization of probiotics is hindered by the harsh conditions of gastrointestinal tract (GIT). Here, we devised a straightforward yet potent modified prebiotic-based “shield” (Gelatin-Inulin, GI), employing dietary inulin and natural polymer gelatin crosslinked <em>via</em> hydrogen bonding for enveloping <em>Lactobacillus reuteri</em> (<em>Lr</em>) to formulate synbiotic hydrogel capsules (<em>Lr</em>@Gl). The GI “shield” serves as a dynamic barrier, augmenting the resistance of <em>Lr</em> to gastric acid and facilitating its bioactivity and adherence in the GIT, synergizing with <em>Lr</em> to elicit an anti-tumor effect. Simultaneously, <em>Lr</em>@GI demonstrates anti-tumor effects by depleting glutathione to release reactive oxygen species, accompanied by the activation of NLRP3 (NOD-like receptor family pyrin domain containing 3), and the induction M1 macrophage polarization. Furthermore, <em>Lr</em>@GI can not only promote the recovery of intestinal barrier but also regulate intestinal flora, promoting the production of SCFAs and further exerting anti-tumor effect. Crucially, <em>Lr</em>@GI also potentiates the anti-tumor effect of 5-Fluorouracil. The construction and synergistic anti-tumor mechanism of synbiotic hydrogel capsules system provide valuable insights for gut microbial tumor therapy.</div></div>","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":"15 8","pages":"Pages 4225-4247"},"PeriodicalIF":14.6,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144863249","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

Advances in immunoPET/SPECT imaging: The role of Fab and F(ab′)2 fragments in theranostics 免疫pet /SPECT成像的进展：Fab和F(ab ')2片段在治疗中的作用

IF 14.6 1区医学

Acta Pharmaceutica Sinica. B Pub Date : 2025-08-01 DOI: 10.1016/j.apsb.2025.05.030

Wenpeng Huang , Jingwei Zhou , Yanchen Liu , Yihan Yang , Rachel J. Saladin , Jessica C. Hsu , Weibo Cai , Lei Kang

{"title":"Advances in immunoPET/SPECT imaging: The role of Fab and F(ab′)2 fragments in theranostics","authors":"Wenpeng Huang , Jingwei Zhou , Yanchen Liu , Yihan Yang , Rachel J. Saladin , Jessica C. Hsu , Weibo Cai , Lei Kang","doi":"10.1016/j.apsb.2025.05.030","DOIUrl":"10.1016/j.apsb.2025.05.030","url":null,"abstract":"<div><div>With the advent of precision medicine and personalized treatment, targeted therapies have become pivotal in oncology. Noninvasive molecular imaging, especially immunoPET/SPECT, plays a crucial role in refining cancer diagnostics and treatment monitoring by visualizing biological processes at the molecular level. This review explores the dynamic field of immunoPET/SPECT imaging using Fab and F(ab′)<sub>2</sub> fragments, characterized by advantageous pharmacokinetics and swift clearance from the bloodstream, making them suitable for same-day imaging procedures. We examine contemporary strategies for radiolabeling these fragments with PET and SPECT radionuclides and discuss potential advancements and the challenges anticipated in the further development of Fab and F(ab′)<sub>2</sub> fragments. Despite the complexities involved in their development, these fragments hold significant promise for advanceing personalized cancer treatment. Keys to this advancement are innovative radiolabeling techniques, site-specific conjugation chemistries, and short-lived radionuclides, all of which are crucial for overcoming existing limitations and enhancing the clinical utility of these imaging agents. As research progresses, Fab and F(ab′)<sub>2</sub> fragments are expected to become central to the future of cancer diagnostics and therapeutic monitoring, thereby improving patient management and contributing significantly to the evolution of personalized medicine.</div></div>","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":"15 8","pages":"Pages 3888-3924"},"PeriodicalIF":14.6,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144863334","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

Engineering strategies of sequential drug delivery systems for combination tumor immunotherapy 肿瘤免疫联合治疗序贯给药系统的工程策略

IF 14.6 1区医学

Acta Pharmaceutica Sinica. B Pub Date : 2025-08-01 DOI: 10.1016/j.apsb.2025.05.039

Zhenyu Xu , Siyan Liu , Yanan Li , Yanping Wu , Jiasheng Tu , Qian Chen , Chunmeng Sun

{"title":"Engineering strategies of sequential drug delivery systems for combination tumor immunotherapy","authors":"Zhenyu Xu , Siyan Liu , Yanan Li , Yanping Wu , Jiasheng Tu , Qian Chen , Chunmeng Sun","doi":"10.1016/j.apsb.2025.05.039","DOIUrl":"10.1016/j.apsb.2025.05.039","url":null,"abstract":"<div><div>Over the past few decades, tumor immunotherapy has revolutionized the landscape of cancer clinical treatment. There is a flourishing development of combination strategies to improve the anti-tumor efficacy of mono-immunotherapy. However, instead of a straightforward combination of multiple therapeutics, it is more preferable to pursue a synergistic effect by designing rational combinations as well as administration strategies, which are based on a comprehensive understanding of the physiological and pathological features. In this case, the timing and spatial distribution of the combination drugs become essential factors in achieving improved therapeutic outcomes. Therefore, the concept of Sequential Drug Delivery System (SDDS) is proposed to define the spatiotemporally programmed drug delivery/release through triggers of internal conditions and/or external interventions, thus complying with the dynamic disease evolution and the human immunity. This review summarizes the recent advancements in biomaterial-based SDDSs used for spatiotemporally-tuned combination tumor immunotherapy. Furthermore, the rationales behind various engineering strategies are discussed. Finally, an overview of potential synergistic mechanisms as well as their prospects for combination immunotherapy is presented.</div></div>","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":"15 8","pages":"Pages 3951-3977"},"PeriodicalIF":14.6,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144863336","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

Targeted inhibition of macrophage STING signaling alleviates inflammatory injury and ventricular remodeling in acute myocardial infarction 靶向抑制巨噬细胞STING信号可减轻急性心肌梗死的炎症损伤和心室重构

IF 14.6 1区医学

Acta Pharmaceutica Sinica. B Pub Date : 2025-08-01 DOI: 10.1016/j.apsb.2025.06.014

Huan Yao , Qingman He , Shujun Wei , Li Xiang , Yuanyuan Luo , Cong Huang , Weiwei Liu , Chuan Zheng , Xueping Li , Yongxiang Gao

{"title":"Targeted inhibition of macrophage STING signaling alleviates inflammatory injury and ventricular remodeling in acute myocardial infarction","authors":"Huan Yao , Qingman He , Shujun Wei , Li Xiang , Yuanyuan Luo , Cong Huang , Weiwei Liu , Chuan Zheng , Xueping Li , Yongxiang Gao","doi":"10.1016/j.apsb.2025.06.014","DOIUrl":"10.1016/j.apsb.2025.06.014","url":null,"abstract":"<div><div>Mitochondrial DNA (mtDNA) acts as a damage-associated molecular pattern to activate the stimulator of interferon genes (STING) signaling in macrophages, promoting tissue inflammation. However, its role in acute myocardial infarction (AMI) remains unclear. Macrophage-specific <em>Sting1</em> knockout mice were used to validate STING's pathological role in AMI. Cardiac and liver mtDNA were used to activate macrophages in co-culture systems with cardiomyocytes to assess fibrosis and hypertrophy. Panaxatriol saponin (PTS) was tested for its ability to block mtDNA-driven macrophage activation and subsequent cardiomyocyte damage. STING–PTS binding ability was analyzed. AMI rats received PTS to evaluate its effects on myocardial inflammation and ventricular remodeling. <em>In vivo</em>, macrophage-specific <em>Sting1</em> knockout reduced myocardial inflammation and injury after AMI. <em>In vitro</em>, mtDNA-activated macrophages induced cardiomyocyte fibrosis and hypertrophy through STING signaling. PTS suppressed mtDNA-driven macrophage activation by directly binding STING, thereby blocking inflammatory cascades. In AMI rats, PTS treatment attenuated acute inflammation and reversed ventricular remodeling. These findings establish the mtDNA–STING axis in macrophages as a critical driver of post-AMI inflammation and identify pharmacological STING inhibition with PTS as a promising therapeutic strategy. The study bridges genetic validation with translational applications, highlighting macrophage STING as a novel target for ischemic heart disease management.</div></div>","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":"15 8","pages":"Pages 4030-4046"},"PeriodicalIF":14.6,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144863340","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

Targeting the coronavirus membrane protein: A promising novel therapeutic strategy 靶向冠状病毒膜蛋白：一种有前景的新治疗策略

IF 14.6 1区医学

Acta Pharmaceutica Sinica. B Pub Date : 2025-08-01 DOI: 10.1016/j.apsb.2025.05.029

Dazhou Shi , Chunhua Ma , Shujing Xu , Peng Zhan

引用次数: 0