Acta Pharmaceutica Sinica. B最新文献

Nose-to-brain delivery of targeted lipid nanoparticles as two-pronged β-amyloid nanoscavenger for Alzheimer's disease therapy 靶向脂质纳米颗粒作为双管齐下的β-淀粉样蛋白纳米清道夫用于阿尔茨海默病的治疗

IF 14.7 1区医学

Acta Pharmaceutica Sinica. B Pub Date : 2025-06-01 DOI: 10.1016/j.apsb.2025.02.035

Yanyan Xu , Xiangtong Ye , Yanfeng Du , Wenqin Yang , Fan Tong , Wei Li , Qianqian Huang , Yongke Chen , Hanmei Li , Huile Gao , Weiwei Zhang

{"title":"Nose-to-brain delivery of targeted lipid nanoparticles as two-pronged β-amyloid nanoscavenger for Alzheimer's disease therapy","authors":"Yanyan Xu , Xiangtong Ye , Yanfeng Du , Wenqin Yang , Fan Tong , Wei Li , Qianqian Huang , Yongke Chen , Hanmei Li , Huile Gao , Weiwei Zhang","doi":"10.1016/j.apsb.2025.02.035","DOIUrl":"10.1016/j.apsb.2025.02.035","url":null,"abstract":"<div><div>Alzheimer's disease (AD), characterized by <em>β</em>-amyloid (A<em>β</em>) aggregation and neuroinflammation, remains a formidable clinical challenge. Herein, we present an innovative nose-to-brain delivery platform utilizing lactoferrin (Lf)-functionalized lipid nanoparticles (LNPs) co-encapsulating <em>α</em>-mangostin (<em>α</em>-M) and <em>β</em>-site APP cleaving enzyme 1 (BACE1) siRNA (siB). This dual-modal therapeutic system synergistically combines the neuroprotective and microglia-reprogramming capabilities of <em>α</em>-M with the transcriptional silencing of BACE1 <em>via</em> siB, thereby simultaneously inhibiting A<em>β</em> production and enhancing its clearance. Fabricated <em>via</em> a microfluidic approach, the LNPs exhibited uniform particle size distribution, great encapsulation efficiency, and robust colloidal stability. Upon intranasal administration, Lf-functionalization enabled superior brain-targeting efficacy through receptor-mediated transcytosis. <em>In vitro</em> studies demonstrated that <em>α</em>-M reversed A<em>β</em>-induced low-density lipoprotein receptor downregulation, promoting microglial phagocytosis and autophagic degradation of A<em>β</em>, while siB effectively suppressed BACE1 expression, abrogating A<em>β</em> synthesis. <em>In vivo</em> investigations in APP/PS1 transgenic mice revealed remarkable cognitive recovery, substantial A<em>β</em> plaque reduction, and alleviation of neuroinflammation and oxidative stress. This intricately designed LNP system, exploiting a non-invasive and efficient nose-to-brain delivery route, provides a biocompatible, synergistic, and transformative therapeutic strategy for the multifaceted management of AD.</div></div>","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":"15 6","pages":"Pages 2884-2899"},"PeriodicalIF":14.7,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144471779","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

Self-degradable “gemini-like” ionizable lipid-mediated delivery of siRNA for subcellular-specific gene therapy of hepatic diseases 自降解的“双子星样”可电离脂质介导siRNA递送用于肝脏疾病的亚细胞特异性基因治疗

IF 14.7 1区医学

Acta Pharmaceutica Sinica. B Pub Date : 2025-06-01 DOI: 10.1016/j.apsb.2025.04.003

Qiu Wang , Bin Wan , Yao Feng , Zimeng Yang , Dan Li , Fan Liu , Ya Gao , Chang Li , Yanhua Liu , Yongbing Sun , Zhonggui He , Cong Luo , Jin Sun , Qikun Jiang

{"title":"Self-degradable “gemini-like” ionizable lipid-mediated delivery of siRNA for subcellular-specific gene therapy of hepatic diseases","authors":"Qiu Wang , Bin Wan , Yao Feng , Zimeng Yang , Dan Li , Fan Liu , Ya Gao , Chang Li , Yanhua Liu , Yongbing Sun , Zhonggui He , Cong Luo , Jin Sun , Qikun Jiang","doi":"10.1016/j.apsb.2025.04.003","DOIUrl":"10.1016/j.apsb.2025.04.003","url":null,"abstract":"<div><div>Tailored lipid nanoparticles (LNPs)-mediated small interfering RNA (siRNA) nanomedicines show promise in treating liver disease, such as acute liver injury (ALI) and non-alcoholic steatohepatitis (NASH). However, constructing LNPs that address biosafety concerns, ensure efficient delivery, and target specific hepatic subcellular fractions has been challenging. To evade above obstacles, we develop three novel self-degradable “gemini-like” ionizable lipids (SS-MA, SS-DC, SS-MH) by incorporating disulfide bonds and modifying the length of ester bond and tertiary amino head. Our findings reveal that the disulfide-bond-bridged LNPs exhibit reduction-responsive drug release, improving both biosafety and siRNA delivery efficiency. Furthermore, the distance of ester bond and tertiary amino head significantly influences the LNPs’ p<em>K</em><sub>a</sub>, thereby affecting endosomal escape, hemolytic efficiency, absorption capacity of ApoE, uptake efficiency of hepatocytes and liver accumulation. We also develop the modified-mannose LNPs (M-LNP) to target liver macrophages specifically. The optimized M-MH_LNP@TNF<em>α</em> exhibits potential in preventing ALI by decreasing tumor necrosis factor <em>α</em> (TNF<em>α</em>) levels in the macrophages, while MH_LNP@DGAT2 could treat NASH by selectively degrading diacylglycerol <em>O</em>-acyltransferase 2 (DGAT2) in the hepatocytes. Our findings provide new insights into developing novel highly effective and low-toxic “gemini-like” ionizable lipids for constructing LNPs, potentially achieving more effective treatment for hepatic diseases.</div></div>","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":"15 6","pages":"Pages 2867-2883"},"PeriodicalIF":14.7,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144471803","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

Phenotypic screening uncovered anti-myocardial fibrosis candidates using a novel 3D myocardial tissue under hypoxia 表型筛选发现抗心肌纤维化候选人使用新的3D心肌组织缺氧

IF 14.7 1区医学

Acta Pharmaceutica Sinica. B Pub Date : 2025-06-01 DOI: 10.1016/j.apsb.2025.04.025

Jingyu Wang , Xiangning Liu , Rongxin Zhu , Ying Sun , Boyang Jiao , Keyan Wang , Yong Jiang , Yong Wang , Chun Li , Wei Wang

{"title":"Phenotypic screening uncovered anti-myocardial fibrosis candidates using a novel 3D myocardial tissue under hypoxia","authors":"Jingyu Wang , Xiangning Liu , Rongxin Zhu , Ying Sun , Boyang Jiao , Keyan Wang , Yong Jiang , Yong Wang , Chun Li , Wei Wang","doi":"10.1016/j.apsb.2025.04.025","DOIUrl":"10.1016/j.apsb.2025.04.025","url":null,"abstract":"<div><div>Myocardial fibrosis (MF) is a common pathological hallmark of cardiovascular diseases, reflecting shared mechanisms in their progression. However, the lack of reliable MF models that accurately mimic its pathogenesis has hindered drug discovery, highlighting the urgent need for more effective therapeutic agents. Herein, a novel contractile three-dimensional (3D) myocardial tissue model integrating cardiomyocytes, cardiac-fibroblasts, and bone marrow-derived macrophages in collagen hydrogel was developed to simulate the fibrotic changes of cardiovascular disease, and facilitate the screening of anti-MF compounds. The 3D myocardial tissue model exhibited precise, visualizable, and quantifiable contractile characteristics under hypoxia and drug interventions. 76 compounds extracted from the resins of <em>Toxicodendron vernicifluum</em>, a traditional Chinese medicine with clear clinical benefits for fibrotic diseases, were screened for anti-fibrotic activity. Using an <em>in vitro</em> 3D oxygen–glucose deprivation (OGD)-treated myocardial tissue model instead of a two-dimensional transforming growth factor-<em>β</em> treated cardiac-fibroblasts model, two candidates including LQ-40 and SQ-3 exert impressive anti-MF activity, which was further validated in left anterior descending coronary artery ligation-induced MF mouse model. The current results demonstrate the feasibility and advantage of the novel contractile 3D tissue model with multi-cell types in discovering candidates for MF, further stressing the great potential of regulating macrophages in the treatment of MF.</div></div>","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":"15 6","pages":"Pages 3008-3024"},"PeriodicalIF":14.7,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144472228","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

Publisher erratum to “Fenofibrate-promoted hepatomegaly and liver regeneration are PPARα-dependent and partially related to the YAP pathway” [Acta Pharmaceutica Sinica B 14 (2024) 2992–3008] “非诺贝特促进的肝脏扩大和肝脏再生是ppar α依赖的，部分与YAP途径相关”的出版商更正[药物学报B 14 (2024) 2992-3008]

IF 14.7 1区医学

Acta Pharmaceutica Sinica. B Pub Date : 2025-06-01 DOI: 10.1016/j.apsb.2025.04.016

Shicheng Fan , Yue Gao , Pengfei Zhao , Guomin Xie , Yanying Zhou , Xiao Yang , Xuan Li , Shuaishuai Zhang , Frank J. Gonzalez , Aijuan Qu , Min Huang , Huichang Bi

引用次数: 0

Discovery of papyifuran A as an unusual cembrane diterpenoid from Boswellia papyrifera resin reveals EEF2 as a potent new drug target for fibrosis of multiple organs 纸莎草树脂中罕见的膜二萜类化合物纸莎草酰胺A的发现表明EEF2是治疗多器官纤维化的强有力的新药物靶点

IF 14.7 1区医学

Acta Pharmaceutica Sinica. B Pub Date : 2025-06-01 DOI: 10.1016/j.apsb.2025.04.004

Madhu Babu Sura , Yeting Zhou , Jijun Li, Yongxian Cheng

{"title":"Discovery of papyifuran A as an unusual cembrane diterpenoid from Boswellia papyrifera resin reveals EEF2 as a potent new drug target for fibrosis of multiple organs","authors":"Madhu Babu Sura , Yeting Zhou , Jijun Li, Yongxian Cheng","doi":"10.1016/j.apsb.2025.04.004","DOIUrl":"10.1016/j.apsb.2025.04.004","url":null,"abstract":"<div><div>Chronic kidney disease (CKD) affects 8%–15% of the population globally and can cause renal failure, partly due to lack of effective treatments and drug targets. Three novel cembrane diterpenoids papyifurans A‒C (<strong>1</strong>–<strong>3</strong>), in particular of <strong>1</strong> with an unprecedented trioxatetracyclo[10.2.1.1<sup>2,5</sup>.1<sup>6,9</sup>]heptadecane polyether scaffold, derived from <em>Boswellia papyrifera</em> resin, were found to effectively protect against renal fibrosis <em>in vitro</em> and <em>in vivo</em>. Their structures were fully characterized using a combination of spectroscopic, computational, modified Mosher’s, and X-ray crystallographic analysis. In particular, we performed chemical proteomic analyses and found that Elongation factor 2 (EEF2) is the key target of compound <strong>1</strong> for anti-renal fibrosis <em>in vitro</em>. Moreover, previous studies have linked EEF2 with lung fibrosis, while compound <strong>1</strong> was found to inhibit the hallmarks of organ fibrosis <em>in vitro.</em> Such effects were observed to decrease with the knock down of EEF2 <em>in vitro</em>, suggesting that EEF2 might be a universal drug target of organ fibrosis. Collectively, the present study demonstrated an example of identifying drug targets by using structurally novel natural products, which will be beneficial for developing therapeutic agents against organ fibrosis.</div></div>","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":"15 6","pages":"Pages 3181-3195"},"PeriodicalIF":14.7,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144472307","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

Obesity–cancer axis crosstalk: Molecular insights and therapeutic approaches 肥胖-癌症轴串扰：分子洞察和治疗方法

IF 14.7 1区医学

Acta Pharmaceutica Sinica. B Pub Date : 2025-06-01 DOI: 10.1016/j.apsb.2025.04.029

Ahmed Rakib, Md Abdullah Al Mamun, Mousumi Mandal, Priti Sinha, Udai P. Singh

{"title":"Obesity–cancer axis crosstalk: Molecular insights and therapeutic approaches","authors":"Ahmed Rakib, Md Abdullah Al Mamun, Mousumi Mandal, Priti Sinha, Udai P. Singh","doi":"10.1016/j.apsb.2025.04.029","DOIUrl":"10.1016/j.apsb.2025.04.029","url":null,"abstract":"<div><div>Now recognized as a global health crisis, obesity has been linked to an increased risk of many types of cancer, including those of the breast, colon, rectum, uterus, gallbladder, and ovary. Obesity and cancer share several characteristics at the cellular, molecular, and epigenetic levels. Obesity is characterized by chronic inflammation of the adipose tissue (AT), resulting in genotoxic stress that further induces metabolic complications and contributes to the initiation and progression of cancer. The excessive accumulation of AT provides adipokines and lipids to engage tumor cells with stromal and immune cells to infiltrate carcinomas and secrete a plethora of cytokines, chemokines, and growth factors within the tumor microenvironment (TME) that contribute to carcinogenesis. Obesity also alters the metabolic reprogramming of immune cells, including macrophages, neutrophils, and T cells, thereby providing a suitable environment for the growth and progression of cancer. Obesity-associated metabolic dysregulation also perturbs the gut microbiome, which produces metabolites that can further increase the risk of cancer progression. This review will discuss links between obesity and cancer progression, including several crucial pathways that bridge the crosstalk between obesity-associated changes in AT inflammation, immune cells, adipokines, chemokines, and tumor cells to support cancer progression. We will also discuss our insights into the mechanisms by which obesity-driven factors influence metabolic reprogramming and touch base on how obesity mediates microbiome dysbiosis to alter metabolite and affect cancer progression. Altogether, this review highlights the crossroads of the obesity–cancer axis, describes its salient features, and presents possible therapeutic approaches for obesity-related cancers.</div></div>","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":"15 6","pages":"Pages 2930-2944"},"PeriodicalIF":14.7,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144471856","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

RBM14 enhances transcriptional activity of p23 regulating CXCL1 expression to induce lung cancer metastasis RBM14增强p23的转录活性，调控CXCL1的表达，诱导肺癌转移

IF 14.7 1区医学

Acta Pharmaceutica Sinica. B Pub Date : 2025-06-01 DOI: 10.1016/j.apsb.2025.03.048

Wen Zhang , Yulin Peng , Meirong Zhou , Lei Qian , Yilin Che , Junlin Chen , Wenhao Zhang , Chengjian He , Minghang Qi , Xiaohong Shu , Manman Tian , Xiangge Tian , Yan Tian , Sa Deng , Yan Wang , Xiaokui Huo , Zhenlong Yu , Xiaochi Ma

{"title":"RBM14 enhances transcriptional activity of p23 regulating CXCL1 expression to induce lung cancer metastasis","authors":"Wen Zhang , Yulin Peng , Meirong Zhou , Lei Qian , Yilin Che , Junlin Chen , Wenhao Zhang , Chengjian He , Minghang Qi , Xiaohong Shu , Manman Tian , Xiangge Tian , Yan Tian , Sa Deng , Yan Wang , Xiaokui Huo , Zhenlong Yu , Xiaochi Ma","doi":"10.1016/j.apsb.2025.03.048","DOIUrl":"10.1016/j.apsb.2025.03.048","url":null,"abstract":"<div><div>Metastasis serves as an indicator of malignancy and is a biological characteristic of carcinomas. Epithelial–mesenchymal transition (EMT) plays a key role in the promotion of tumor invasion and metastasis and in the enhancement of tumor cell aggressiveness. Prostaglandin E synthase 3 (p23) is a cochaperone for heat shock protein 90 (HSP90). Our previous study showed that p23 is an HSP90-independent transcription factor in cancer-associated inflammation. The effect and mechanism of action of p23 on lung cancer metastasis are tested in this study. By utilizing cell models <em>in vitro</em> and mouse tail vein metastasis models <em>in vivo</em>, the results provide solid evidence that p23 is critical for promoting lung cancer metastases by regulating downstream CXCL1 expression. Rather than acting independently, p23 forms a complex with RNA-binding motif protein 14 (RBM14) to facilitate EMT progression in lung cancer. Therefore, our study provides evidence for the potential role of the RBM14–p23–CXCL1–EMT axis in the metastasis of lung cancer.</div></div>","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":"15 6","pages":"Pages 3059-3072"},"PeriodicalIF":14.7,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144471857","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

Alginate lyase immobilized Chlamydomonas algae microrobots: minimally invasive therapy for biofilm penetration and eradication 海藻酸解酶固定化衣藻微机器人：生物膜穿透和清除的微创治疗

IF 14.7 1区医学

Acta Pharmaceutica Sinica. B Pub Date : 2025-06-01 DOI: 10.1016/j.apsb.2025.03.034

Xiaoting Zhang , Huaan Li , Lu Liu , Yanzhen Song , Lishan Zhang , Jiajun Miao , Jiamiao Jiang , Hao Tian , Chang Liu , Fei Peng , Yingfeng Tu

{"title":"Alginate lyase immobilized Chlamydomonas algae microrobots: minimally invasive therapy for biofilm penetration and eradication","authors":"Xiaoting Zhang , Huaan Li , Lu Liu , Yanzhen Song , Lishan Zhang , Jiajun Miao , Jiamiao Jiang , Hao Tian , Chang Liu , Fei Peng , Yingfeng Tu","doi":"10.1016/j.apsb.2025.03.034","DOIUrl":"10.1016/j.apsb.2025.03.034","url":null,"abstract":"<div><div>Bacterial biofilms can make traditional antibiotics impenetrable and even promote the development of antibiotic-resistant strains. Therefore, non-antibiotic strategies to effectively penetrate and eradicate the formed biofilms are urgently needed. Here, we demonstrate the development of self-propelled biohybrid microrobots that can enhance the degradation and penetration effects for <em>Pseudomonas aeruginosa</em> biofilms in minimally invasive strategy. The biohybrid microrobots (CR@Alg) are constructed by surface modification of <em>Chlamydomonas reinhardtii</em> (CR) microalgae with alginate lyase (Alg) <em>via</em> biological orthogonal reaction. By degrading the biofilm components, the number of CR@Alg microrobots with fast-moving capability penetrating the biofilm increases by around 2.4-fold compared to that of microalgae. Massive reactive oxygen species are subsequently generated under laser irradiation due to the presence of chlorophyll, inherent photosensitizers of microalgae, thus triggering photodynamic therapy (PDT) to combat bacteria. Our algae-based microrobots with superior biocompatibility eliminate biofilm-infections efficiently and tend to suppress the inflammatory response <em>in vivo</em>, showing huge promise for the active treatment of biofilm-associated infections.</div></div>","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":"15 6","pages":"Pages 3259-3272"},"PeriodicalIF":14.7,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144472297","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

Editor Profiles: Guest Editors of Special Column on Nanomedicines for Tumor Microenvironment Modulation 编辑简介：肿瘤微环境调节纳米药物特约专栏客座编辑

IF 14.7 1区医学

Acta Pharmaceutica Sinica. B Pub Date : 2025-06-01 DOI: 10.1016/j.apsb.2025.05.026

引用次数: 0

Unveiling the metabolic fate of drugs through metabolic reaction-based molecular networking 通过基于代谢反应的分子网络揭示药物的代谢命运

IF 14.7 1区医学

Acta Pharmaceutica Sinica. B Pub Date : 2025-06-01 DOI: 10.1016/j.apsb.2025.03.050

Haodong Zhu , Xupeng Tong , Qi Wang , Aijing Li , Zubao Wu , Qiqi Wang , Pei Lin , Xinsheng Yao , Liufang Hu , Liangliang He , Zhihong Yao

{"title":"Unveiling the metabolic fate of drugs through metabolic reaction-based molecular networking","authors":"Haodong Zhu , Xupeng Tong , Qi Wang , Aijing Li , Zubao Wu , Qiqi Wang , Pei Lin , Xinsheng Yao , Liufang Hu , Liangliang He , Zhihong Yao","doi":"10.1016/j.apsb.2025.03.050","DOIUrl":"10.1016/j.apsb.2025.03.050","url":null,"abstract":"<div><div>Effective annotation of <em>in vivo</em> drug metabolites using liquid chromatography-mass spectrometry (LC–MS) remains a formidable challenge. Herein, a metabolic reaction-based molecular networking (MRMN) strategy is introduced, which enables the “one-pot” discovery of prototype drugs and their metabolites. MRMN constructs networks by matching metabolic reactions and evaluating MS<sup>2</sup> spectral similarity, incorporating innovations and improvements in feature degradation of MS<sup>2</sup> spectra, exclusion of endogenous interference, and recognition of redundant nodes. A minimum 75% correlation between structural similarity and MS<sup>2</sup> similarity of neighboring metabolites was ensured, mitigating false negatives due to spectral feature degradation. At least 79% of nodes, 49% of edges, and 97% of subnetworks were reduced by an exclusion strategy of endogenous ions compared to the Global Natural Products Social Molecular Networking (GNPS) platform. Furthermore, an approach of redundant ions identification was refined, achieving a 10%–40% recognition rate across different samples. The effectiveness of MRMN was validated through a single compound, plant extract, and mixtures of multiple plant extracts. Notably, MRMN is freely accessible online at <span><span>https://yaolab.network</span><svg><path></path></svg></span>, broadening its applications.</div></div>","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":"15 6","pages":"Pages 3210-3225"},"PeriodicalIF":14.7,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144472232","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