Letters in Drug Design & Discovery最新文献

{"title":"Investigating the mechanism of curcumin against LUAD malignant progression and macrophage M2 polarization based on network pharmacology, bioinformatics, and molecular docking","authors":"Ni Zhang, Huan Tian, Qian Huang, Aqing Liu, Fuli Zhang","doi":"10.1016/j.lddd.2025.100140","DOIUrl":"https://doi.org/10.1016/j.lddd.2025.100140","url":null,"abstract":"Lung adenocarcinoma (LUAD) is a subtype of non-small cell lung cancer (NSCLC) that poses significant mortality risks. Curcumin, a natural polyphenolic compound with documented anti-inflammatory and anti-cancer properties, has not been comprehensively investigated in the context of LUAD pathogenesis. Cell counting kit-8 (CCK-8), 5-ethynyl-2'-deoxyuridine (EdU) staining, flow cytometry, wound healing, and transwell assays were used to assess cellular functions. Gene expression was quantified by quantitative real-time polymerase chain reaction (qRT-PCR) and western blot. To evaluate macrophage polarization, flow cytometry was additionally performed. Network pharmacology analysis and molecular docking simulation were used to predict the potential targets of curcumin in LUAD. The xenograft mice were established for in vivo validation, with immunohistochemistry (IHC) employed for gene expression analysis. Curcumin exhibited inhibitory effects on the malignant behaviors of LUAD and macrophage M2 polarization. A total of 129 common targets of curcumin were screened in LUAD, and cyclin A2 (CCNA2) was identified as the core target by molecular docking. Mechanistically, curcumin reduced CCNA2 expression and acted as a repressor through the CCNA2-activated protein kinase B/signal transducer and activator of transcription (AKT/STAT) pathway. Similarly, curcumin suppressed tumor growth in vivo through suppressing CCNA2. In this study, curcumin demonstrates inhibitory effects on the malignant progression of LUAD and macrophage M2 polarization by modulating CCNA2 expression through the AKT/STAT pathway. This finding is the first to demonstrate the molecular mechanism of curcumin in the treatment of LUAD through the combination of bioinformatics analysis, network pharmacology, molecular docking, and biological experiments. Curcumin promotes apoptosis of LUAD cells, inhibits proliferation, migration, and invasion, as well as M2 polarization of macrophages by down-regulating CCNA2 based on molecular docking.","PeriodicalId":18059,"journal":{"name":"Letters in Drug Design & Discovery","volume":"22 8","pages":"100140-100140"},"PeriodicalIF":0.0,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147891025","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":"Investigating the therapeutic potential of jiawei xuanbi decoction in rheumatoid arthritis via network pharmacology and cell experiments","authors":"Jiakang Cui, Jinjin Li, Mengjiao Liu, Yongzheng Deng, Jinzhong Xian, Junfu Ma, Xiao Chen, Zengyu Cheng, Qingliang Meng","doi":"10.1016/j.lddd.2025.100141","DOIUrl":"https://doi.org/10.1016/j.lddd.2025.100141","url":null,"abstract":"Rheumatoid arthritis (RA) is an autoimmune disease marked by symmetrical chronic polyarticular inflammation, which may increase the risk of disability in severe cases. Jiawei Xuanbi Decoction (JWXB), a traditional Chinese medicine formula, is commonly used for treating RA, but its specific molecular targets and action mechanisms in treating the disease remain unclear. RAW264.7 cells were induced to differentiate into osteoclasts by receptor activator of nuclear factor κ-B ligand (RANKL), and cell viability was evaluated via the MTT assay. Components of JWXB and RA-related targets were collected from Chinese Pharmacopoeia, SwissTargetPrediction, SuperPred, and GeneCard. Afterward, a protein-protein interaction (PPI) network was constructed using Cytoscape software. The key common targets were analyzed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses via the DAVID6.8 database. AutoDock Vina software and iMODS platform were employed to perform molecular docking and molecular dynamics (MD) simulation to analyze the binding affinity between JWXB active components and targets. JWXB inhibited RANKL-induced osteoclast differentiation in vitro . A total of 164 targets associated with JWXB and RA were obtained, with AKT1 and STAT3 as key hubs in the PPI network. GO enrichment analysis revealed that these common targets were involved in biological processes like inflammatory response, protein phosphorylation, and regulation of cell proliferation. KEGG pathway analysis demonstrated that they were enriched in pathways including PI3K-Akt, TNF, NF-κB, and osteoclast differentiation pathways. Molecular docking and MD simulation results further confirmed stable binding between active components of JWXB (such as Tetrandrine and Demethyl tetrandrine) and key target genes (AKT1, SRC, and EGFR), with binding energies of all below −5 kcal/mol, indicating strong interactions. JWXB exerts anti-RA effects through multi-target/multi-pathway modulation of inflammation, osteoclast differentiation, and cell proliferation. These findings provide a scientific basis for JWXB’s clinical application and mechanism exploration.","PeriodicalId":18059,"journal":{"name":"Letters in Drug Design & Discovery","volume":"22 8","pages":"100141-100141"},"PeriodicalIF":0.0,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147918880","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":"Exploring the molecular mechanism of Qilian Fuzheng capsule for treatment of non-small cell lung cancer using network pharmacology, RNA-seq, molecular docking and experimental verification","authors":"Xiaoqing Xu, Xin Dai, Yang Zhao, Yuhan Sun, Lin Shi, Yuanfu Qi","doi":"10.1016/j.lddd.2025.100134","DOIUrl":"https://doi.org/10.1016/j.lddd.2025.100134","url":null,"abstract":"Qilian Fuzheng capsule (QL) has been used for the treatment of various malignant tumors, but the underlying mechanisms are largely unclear. In this study, we aimed to explore the effects and potential mechanisms of QL in non-small cell lung cancer (NSCLC) progression. Cell cytotoxicity was tested by CCK-8 assay. Transcriptome sequencing and bioinformatics analysis were used to screen target genes and main pathways of QL in NSCLC. Gene expression was determined by qRT-PCR, western blot and IHC assays. Flow cytometry analysis was adopted to analyze cell cycle and cell apoptosis. EdU assay and colony formation assay were performed to evaluate cell proliferation. Transwell assay was carried out to explore cell migration and invasion. Glycolysis level was estimated through glucose uptake assay kit and lactate assay kit. Murine xenograft model was established to explore the functions of QL in NSCLC in vivo . The PI3K-AKT signaling pathway was verified as the key pathway for the action of QL on NSCLC. QL treatment arrested cell cycle, repressed cell proliferation, migration, invasion, glycolysis and PI3K-AKT pathway and promoted apoptosis in NSCLC cells. Moreover, QL restrained tumor growth in vivo . Next, the network pharmacological analysis of QL in lung cancer was constructed. It was found that Apigenin (API) in TianNanXing (TNX, the component of QL) was the major active component and PI3K-AKT pathway might play a major role in lung cancer treatment. Thereafter, the effect of API on NSCLC was investigated. As a result, API suppressed NSCLC cell growth, migration, invasion and glycolysis and promoted apoptosis and cell cycle arrest, while GLUT1 overexpression restored the effects. Furthermore, API inactivated PI3K-AKT pathway through regulating GLUT1. Based on transcriptome sequencing, we revealed that QL treatment repressed NSCLC progression by regulating PI3K-AKT pathway and GLUT1 expression, indicating that QL might be an effective Chinese patent drug in NSCLC treatment.","PeriodicalId":18059,"journal":{"name":"Letters in Drug Design & Discovery","volume":"22 8","pages":"100134-100134"},"PeriodicalIF":0.0,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147892401","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":"Investigating the neuroprotective effects and the potential mechanisms of β-amyrenone in cerebral ischemic/reperfusion injury based on pharmacology network, bioinformatics, and molecular docking simulation","authors":"Liangji Guo, Jian Li, Chenglong Wang, Jiangcun Wei, Zujie Qin, H. Henry Teng, Xiaoping Mei","doi":"10.1016/j.lddd.2025.100135","DOIUrl":"https://doi.org/10.1016/j.lddd.2025.100135","url":null,"abstract":"Cerebral ischemic/reperfusion injury (CIRI) can cause secondary injury to the neurons, which remains unresolved in the clinic. β-amyrenone harbors anti-inflammatory effects. The present study aims to explore the neuroprotective effects and the underlying mechanisms of β-amyrenone in CIRI based on network pharmacology, bioinformatics, and molecular docking simulation. Network pharmacology was used to screen the potential targets of the main bioactive ingredients of Euonymus fortunei in acute ischemic stroke (IS), and the disease-targets-drugs model was constructed using the Cytoscape software. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed by the Database for Annotation, Visualization, and Integrated Discovery (DAVID). The scores of the top 10 hub targets and the interaction degrees of the main bioactive ingredients were quantified by four algorithms (Degree, Betweenness Centrality, Closeness Centrality, and Neighborhood Connectivity) based on the topological structures of the constructed networks. The potential interactions between β-amyrenone and potential hub targets were predicted by molecular docking simulation. CIRI model was established through oxygen-glucose deprivation/reoxygenation (OGD/R) in neural cells. The neural protective effects of β-amyrenone were tested by cell counting kit-8 assay, enzyme-linked immunosorbent assay and flow cytometry. Reverse-transcription quantitative polymerase chain reaction and western blot were used to detect the influences of β-amyrenone on the levels of screened targets. Interleukin 1β (IL-1β), prostaglandin-endoperoxide synthase 2 (PTGS2), mitogen-activated protein kinase 3 (MAPK3), and estrogen receptor 1 (ESR1) might be the potential hub targets of the main bioactive targets of Euonymus fortunei in acute IS, and β-amyrenone was the core bioactive ingredient of Euonymus fortunei. Results of GO and KEGG pathway enrichment analysis displayed that β-amyrenone might modulate inflammation-related activities in acute IS. β-amyrenone could bind to the amino acid residues of IL-1β, PTGS2, MAPK3, and ESR1 with high affinity. Besides, β-amyrenone treatment increased neural cell viability, reduced the release of inflammatory cytokines, and protected from apoptosis under the OGD/R context. β-amyrenone treatment in neural cells with OGD/R exposure could influence the mRNA and protein levels of IL-1β, PTGS2, MAPK3, and ESR1. β-amyrenone exerts the neuroprotective effects against cerebral ischemic/reperfusion injury, which may be achieved by targeting IL-1β, PTGS2, MAPK3, or ESR1.","PeriodicalId":18059,"journal":{"name":"Letters in Drug Design & Discovery","volume":"22 8","pages":"100135-100135"},"PeriodicalIF":0.0,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147896192","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":"Based on Network Pharmacology and Molecular Docking Simulation: A Study of the Potential Targets and Mechanisms of Hesperetin Action in Ameliorating Henoch-Schönlein Purpura in Children","authors":"Lina Zhao, Xiaojuan He, Xiao‐Lei Hao, Weiyang Lai, Jianhong Zhao, Yiqiao Chen, Yin Yuan","doi":"10.1016/j.lddd.2025.100096","DOIUrl":"https://doi.org/10.1016/j.lddd.2025.100096","url":null,"abstract":"IgA-mediated inflammation and reactive oxygen species production in Henoch-Schönlein purpura (HSP) account for important reasons in human microvascular endothelial cell (HDMVEC) damage. Hesperetin (HST) is a natural flavonoid compound with pharmacological effects such as anti-inflammation, antioxidation, lipid-lowering and cardiovascular protection, and it is widely used in organic chemistry, medicine, agriculture, food and other fields. Here, this study aims to explore the potential mechanisms of HST on HDMVECs based on network pharmacology and molecular docking simulation. CCK8 assay and flow cytometry were utilized to assess the cell viability and apoptotic proportions of HDMVECs, and the levels of tumor necrosis factor-α (TNF-α), interleukin 8 (IL-8), and nitric oxide (NO) were assessed by enzyme-linked immunosorbent assay and Griess reaction. Besides, the abilities of treated HDMVECs to form capillary tubes and migrate were evaluated by tube formation and migration assays, respectively. The pathogenic genes of HSP were retrieved and the intersection is represented by a Venn diagram. The protein-protein interaction (PPI) and core target networks of intersected targets were performed and displayed by the STRING website. The enrichment information of GO and Kyoto Encyclopedia of Gene and Genomics (KEGG) pathways was obtained using the DAVID database and displayed via the SangerBox website. AutoDockTools was applied for the molecular docking. HST increased the viability, angiogenesis, and migration of HDMVECs in the presence of 10 % HSP serum, but reduced the release of inflammatory cytokines (TNF-α and IL-8) as well as NO production. Results of network pharmacology analysis exhibited that HST might target poly (ADP-Ribose) polymerase 1 (PARP1), phosphotidylinositol-4,5-bisphosphate 3-Kinase catalytic subunit alpha (PIK3CA), and caspase 8 (CASP8) in HDMVECs under the HSP context, all of which are involved in the apoptosis pathway, and subsequent molecular docking simulation verified that HST could bind to poly(ADP-ribose) polymerase 1 (PARP1), phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA), and caspase 8 (CASP8) proteins with high affinity. In addition, levels of PARP1 and CASP8 were increased under the HSP condition, but reduced in response to HST treatment. HST can increase the longevity of HDMVECs and enhance their ability to form capillary tubes and migrate, while suppressing the release levels of inflammatory cytokines, along with NO generation under the HSP setting, which may also protect HDMVECs from apoptosis via targeting PARP1 and CASP8.","PeriodicalId":18059,"journal":{"name":"Letters in Drug Design & Discovery","volume":"22 7","pages":"100096-100096"},"PeriodicalIF":0.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147919139","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":"Network pharmacology and experimental verification reveals the anti-growth and anti-migration roles of allicin in non-small cell lung cancer","authors":"Liwei Teng, Hui Chen","doi":"10.1016/j.lddd.2025.100098","DOIUrl":"https://doi.org/10.1016/j.lddd.2025.100098","url":null,"abstract":"Allicin is considered to have anti-tumor activity in lung cancer (LC), but the underlying molecular mechanism remains unclear. This study aimed to evaluate the pharmacological mechanism of allicin against non-small cell lung cancer (NSCLC) using network pharmacological analysis and experimental validation. NSCLC cell lines (A549 and SK-MES-1) were treated with different concentrations of allicin. Cell proliferation, migration and apoptosis were determined using CCK8 assay, colony formation assay, transwell assay and flow cytometry. The potential targets of allicin and LC were screened using network pharmacology, and the 9 core targets with stable binding were molecular-docked with allicin. Functional and pathway enrichment analyses were performed using KEGG and GO analysis. The protein levels of p-EGFR/EGFR, p-PI3K/PI3K and p-AKT/AKT were analyzed using western blot. Allicin reduced NSCLC cell proliferation and migration, while inducing apoptosis in a dose-dependent manner. Network pharmacology and molecular docking were used to explore the potential molecular targets and pathways of allicin affecting LC progression. The results illustrated that EGFR, CASP3, NFKB1, SRC, PARP1, STAT1, MAPK3, MAPK14 and MCL1 were the core targets for the inhibitory effect of allicin on LC. Furthermore, KEGG and GO analysis showed that the anti-cancer role of allicin might be achieved by regulating EGFR/PI3K/AKT pathway. To further confirm this, WB was performed to explore the regulation of allicin on p-EGFR/EGFR, p-PI3K/PI3K and p-AKT/AKT protein levels, and the results confirmed that allicin inhibited the activity of EGFR/PI3K/AKT pathway to suppress NSCLC progression. Allicin restrained NSCLC cell growth and migration via inhibiting the EGFR/PI3K/AKT pathway, suggesting that allicin might be a promising therapeutic agent for NSCLC.","PeriodicalId":18059,"journal":{"name":"Letters in Drug Design & Discovery","volume":"22 7","pages":"100098-100098"},"PeriodicalIF":0.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147877945","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":"Andrographolide inhibits microglia inflammation and M1-like macrophage polarization after traumatic brain injury by regulating BRD4 expression","authors":"Xinjing Liu, C E Zhen, Ting Fu, Hongfei Shao","doi":"10.1016/j.lddd.2025.100093","DOIUrl":"https://doi.org/10.1016/j.lddd.2025.100093","url":null,"abstract":"Traumatic brain injury (TBI) is the leading cause of death and disability in young people. Andrographolide (Andro) has a wide range of therapeutic effects. This study aimed to explore the effects and mechanisms of Andro on TBI therapy. The TBI in vitro cell model was established by treating HMC3 cells with lipopolysaccharide/adenosine triphosphate (LPS/ATP). Cell viability was detected by Cell Counting Kit-8 (CCK-8) assay. The concentrations of inflammatory factors and anti-inflammatory factors were examined with Enzyme-Linked Immunosorbent Assay (ELISA). iNOS, Arg-1 and Bromodomain-containing protein 4 (BRD4) levels were examined by quantitative real-time polymerase chain reaction (qRT-PCR) or western blot. CD86 and CD206 expression was evaluated through flow cytometry analysis. Andro promoted the viability and M2 macrophage polarization, and inhibited inflammation and M1 macrophage polarization in LPS/ATP-induced HMC3 cells. BRD4 level was induced by LPS/ATP in HMC3 cells, while Andro treatment inhibited the effect. Silencing of BRD4 repressed the inflammation and M1 macrophage polarization in LPS/ATP-induced HMC3 cells. Moreover, Andro alleviated LPS/ATP-mediated effects on inflammation and M1 macrophage polarization in HMC3 cells, whereas BRD4 overexpression abated the effects. Andro alleviated LPS/ATP-induced HMC3 cell inflammation and M1 macrophage polarization by modulating BRD4 expression.","PeriodicalId":18059,"journal":{"name":"Letters in Drug Design & Discovery","volume":"22 7","pages":"100093-100093"},"PeriodicalIF":0.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147895881","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":"Uncovering the mechanism of ARRDC3 in non-small cell lung cancer cisplatin resistance and autophagy based on bioinformatics and experimental verification","authors":"Wenjun Tang, Jingru Luo, Shu Lin, Qixing Yan","doi":"10.1016/j.lddd.2025.100097","DOIUrl":"https://doi.org/10.1016/j.lddd.2025.100097","url":null,"abstract":"Cisplatin (DDP) is a commonly used first-line chemotherapy drug for non-small cell lung cancer (NSCLC), but the emergence of DDP resistance greatly reduces its therapeutic effect. Arrestin domain-containing 3 (ARRDC3) has been found to play an anti-cancer role in NSCLC, but whether ARRDC3 regulates DDP resistance in NSCLC is still unclear. The levels of ARRDC3, myeloid ecotropic insertion site 1 (MEIS1), protein kinase AMP-activated catalytic subunit alpha 2 (PRKAA2), and autophagy-related proteins were detected by quantitative real-time PCR (qRT-PCR) or western blot. Cell counting kit 8 (CCK8) assay, 3-(4, 5-dimethyl-2-thiazolyl)−2, 5-diphenyl-2H-tetrazolium bromide (MTT) assay, 5-ethynyl-2′-deoxyuridine (EdU) assay, flow cytometry, and transwell assay were used to measure cell DDP resistance, proliferation, apoptosis and invasion. The interaction between ARRDC3 and MEIS1 or PRKAA2 was confirmed by dual-luciferase reporter assay, chromatin immunoprecipitation (ChIP) assay and Co-immunoprecipitation (Co-IP) assay. Xenograft tumor models were constructed to test the effect of ARRDC3 on NSCLC tumorigenesis and DDP resistance in vivo. ARRDC3 expression was downregulated in DDP-resistant NSCLC tissues and cells. Functional experiments showed that ARRDC3 overexpression restrained DDP resistance, growth, invasion and autophagy in NSCLC cells. Moreover, MEIS1 promoted ARRDC3 transcription by binding to its promoter region, and the inhibitory effects of MEIS1 overexpression on cell DDP resistance, growth, invasion and autophagy were reversed by ARRDC3 knockdown. Besides, ARRDC3 could interact with PRKAA2, and PRKAA2 overexpression also eliminated the regulation of ARRDC3 on cell DDP resistance, growth, invasion and autophagy. Furthermore, MEIS1 decreased PRKAA2 expression by activating ARRDC3 transcription. Additionally, upregulation of ARRDC3 reduced NSCLC tumorigenesis and DDP resistance in vivo. MEIS1-activated ARRDC3 represses NSCLC cell DDP resistance, growth, invasion and autophagy by reducing PRKAA2 expression, confirming the crucial role of MEIS1/ARRDC3/PRKAA2 axis in the chemotherapy resistance of NSCLC.","PeriodicalId":18059,"journal":{"name":"Letters in Drug Design & Discovery","volume":"22 7","pages":"100097-100097"},"PeriodicalIF":0.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147912971","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":"Matrine suppresses the malignant progression of esophageal cancer by inhibiting the expression of CTSB","authors":"Guibin Zhang, Shuhui Gao, Bin Ren, Xiaoning Li","doi":"10.1016/j.lddd.2025.100094","DOIUrl":"https://doi.org/10.1016/j.lddd.2025.100094","url":null,"abstract":"Esophageal cancer (EC), as one of the most common digestive cancers, significantly affects the quality of human life. The aim of this study was to investigate whether matrine-mediated regulation of Cathepsin B (CTSB) affects EC progression. Cell proliferation, apoptosis, and angiogenesis were evaluated using the Methylthiazolyldiphenyl-tetrazolium bromide (MTT) assay, colony formation assay, flow cytometry, and tube formation assay, respectively. Oxidative stress and ferroptosis were assessed by measuring malondialdehyde (MDA), mitochondrial membrane potential (MMP), reactive oxygen species (ROS), and Fe 2+ levels using specific commercial assay kits. RT-qPCR and western blotting were utilized to assess mRNA and protein expression, respectively. A mouse xenograft model was established for the purpose of analysis in vivo . Matrine significantly suppressed EC cell proliferation and angiogenesis, induced apoptosis, oxidative stress, and ferroptosis, and decreased CTSB expression in EC cells. CTSB was highly expressed in EC tissues and cells. CTSB knockdown inhibited the malignant behavior of EC cells. Conversely, CTSB overexpression reversed the inhibitory effects of matrine on EC cell function. Furthermore, matrine significantly suppressed tumor growth in a xenograft model, accompanied by downregulation of CTSB expression in tumor tissues. Matrine suppressed the malignant progression of EC by downregulating CTSB expression, highlighting a potential therapeutic strategy.","PeriodicalId":18059,"journal":{"name":"Letters in Drug Design & Discovery","volume":"22 7","pages":"100094-100094"},"PeriodicalIF":0.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147915096","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":"Network pharmacology prediction and molecular docking-based strategy to explore the potential mechanism of Trigonelline against diabetic nephropathy via targeting MMP9","authors":"Jing Wang, Pengjie Zhang, Nan Bao, Peng Du, Duan Bin, Tong Ding","doi":"10.1016/j.lddd.2025.100095","DOIUrl":"https://doi.org/10.1016/j.lddd.2025.100095","url":null,"abstract":"Diabetic nephropathy (DN) is a renal complication arising from diabetes and represents a leading contributor to end-stage renal disease. Current therapeutic strategies for DN are associated with significant limitations. Trigonelline (TRL), a natural alkaloid derived from fenugreek (T rigonella foenum-graecum L.), has shown promise in mitigating diabetes and its associated complications. This study aims to explore the therapeutic potential of TRL in DN and to elucidate the molecular mechanisms underlying its effects. High glucose (HG) was applied to treat HK-2 cells to establish a cell model of DN. Cell viability was detected by Cell Counting Kit-8 (CCK-8) assay. Apoptosis was identified using flow cytometry. The oxidative stress markers, including superoxide dismutase (SOD), catalase (CAT) and malondialdehyde (MDA), were quantified with the corresponding kits. The concentrations of the inflammatory cytokines interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) secreted by the cells were determined via enzyme-linked immunosorbent assay (ELISA). Network pharmacology was employed to forecast drug targets and disease targets. The binding ability between TRL and matrix metalloproteinase-9 (MMP9) was verified by molecular docking technology. Western blotting was applied to evaluate protein expression. A mouse xenograft model was established for the purpose of analysis in vivo . TRL ameliorated HG-induced HK-2 cell injury. MMP9 was the target of TRL for the treatment of DN. Suppression of MMP9 mitigated damage to HK-2 cells caused by HG. TRL specifically targeted MMP9 in the therapy for DN. TRL mitigated DN-induced renal damage through modulation of MMP9 expression. TRL attenuated renal injury in DN mice by targeting MMP9. The present study revealed the molecular mechanism of TRL targeting MMP9 in the treatment of DN and provided a reference for the wide application of TRL in clinically managing DN.","PeriodicalId":18059,"journal":{"name":"Letters in Drug Design & Discovery","volume":"22 7","pages":"100095-100095"},"PeriodicalIF":0.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147915148","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}