Letters in Drug Design & Discovery最新文献

{"title":"Exploration of the potential molecular mechanism of magnolol in colorectal cancer treatment based on network pharmacology and molecular docking","authors":"Xianghui Liao, Tuhua Li, Li Yang, Haiwen Li, Weiru Li, Yuting Liu, Xie Zhong","doi":"10.1016/j.lddd.2025.100063","DOIUrl":"https://doi.org/10.1016/j.lddd.2025.100063","url":null,"abstract":"Colorectal cancer (CRC) has experienced a global rise in incidence, with chemotherapy resistance becoming a significant challenge during clinical treatment. Magnolol, a natural compound derived from Chinese herbal medicine, has been shown to induce apoptosis in various cancer cell types. However, the identification of comprehensive therapeutic targets and the underlying mechanisms through which magnolol exerts its effects against CRC remain limited. Network pharmacology was employed to forecast drug targets and disease targets. The binding ability between magnolol and the central therapeutic target Cyclin-dependent kinase 4 (CDK4) was verified by molecular docking technology. Cell viability was detected by Cell Counting Kit-8 (CCK-8) assay. RT-qPCR and western blotting were applied to evaluate mRNA and protein expression, respectively. The detection of cell proliferation was carried out by means of colony formation. Cell migration was examined by wound healing assay. Transwell was employed to assess cell invasion. CCK-8 assay was conducted to evaluate the Half maximal inhibitory concentration (IC50) value of 5-Fluorouracil (5-FU) in DLD1 and SW620 cells. The binding affinity between forkhead box protein A 2 (FOXA2) and CDK4 was validated with Chromatin Immunoprecipitation (ChIP) and dual-luciferase reporter gene assay. A mouse xenograft model was established for the purpose of analysis in vivo . CDK4 was a potential target for magnolol in the treatment of CRC. Magnolol suppressed the expression of CDK4. Magnolol targeted CDK4 and inhibited CRC cell migration, invasion, and 5-FU resistance. Magnolol influenced CDK4 expression by regulating FOXA2. Magnolol modulated CRC cell function via the FOXA2/CDK4 pathway. Magnolol restrained CRC tumor growth by reducing FOXA2 expression. Magnolol inhibited the malignant progression and 5-FU resistance of CRC by targeting the FOXA2/CDK4 axis.","PeriodicalId":18059,"journal":{"name":"Letters in Drug Design & Discovery","volume":"22 7","pages":"100063-100063"},"PeriodicalIF":0.0,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147881495","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":"Fosinopril ameliorates renal injury in diabetic nephropathy by inactivating the SRC/NF-κB pathway","authors":"Xiaofeng Cheng, Zhengbo Qiao, Li Cheng, Kai Wang","doi":"10.1016/j.lddd.2025.100062","DOIUrl":"https://doi.org/10.1016/j.lddd.2025.100062","url":null,"abstract":"Diabetic nephropathy (DN) is a serious complication of diabetes, characterized by renal tissue injury. Fosinopril, an ACE inhibitor, has been shown to have renoprotective effects in DN, but the underlying mechanisms are not fully understood. A mouse model of DN was established by administering streptozotocin (STZ) to C57BL/6J mice. The effects of fosinopril on renal tissue injury were assessed by administering the drug orally for 8 weeks. Serum creatinine (Scr) and blood urea nitrogen (BUN) levels were measured through colorimetric methods, and blood glucose levels were determined using a glucometer. Histopathological changes in renal tissues were evaluated using hematoxylin and eosin staining, PAS staining, and Masson’s trichrome staining. HK2 cells were stimulated with high glucose and TGF-β1 to mimic DN-like cell injury. Enzyme-linked immunosorbent assays (ELISAs) were performed to detect levels of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and interleukin-1β (IL-1β). TUNEL assay was employed to evaluate cell apoptosis, while colorimetric assays were utilized to determine the levels of malondialdehyde (MDA) and superoxide dismutase (SOD). Reactive oxygen species (ROS) levels were assessed using a fluorometric assay. Cell viability was analyzed by a cell counting kit-8 (CCK-8) assay, and flow cytometry was used to assess cell apoptosis. Network pharmacology analysis was conducted to identify the protein target of fosinopril in DN. Protein expression was detected by western blotting assay. Fosinopril administration effectively mitigated renal injury in STZ-induced DN mice by reducing levels of kidney function and inflammatory markers, improving histological parameters, and normalizing the balance of apoptosis and oxidative stress. Network pharmacology analysis identified SRC as a target of fosinopril in DN. In addition, overexpression of SRC attenuated the inhibitory effects of fosinopril on inflammation, apoptosis, and oxidative stress in HG-induced HK2 cells. Furthermore, fosinopril ameliorated inactivated the NF-κB pathway through the regulation of SRC. These findings suggest that fosinopril may be an effective therapeutic option for the management of DN by inactivating the SRC/NF-κB pathway, which could have significant clinical implications in the treatment of patients with DN.","PeriodicalId":18059,"journal":{"name":"Letters in Drug Design & Discovery","volume":"22 7","pages":"100062-100062"},"PeriodicalIF":0.0,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147910388","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":"Ginsenoside Rh3 suppresses cell proliferation, metastasis, and oxidative stress of colorectal cancer via targeting HSP90AA1","authors":"Pintian Lv, Bin Ren, Gang Cheng","doi":"10.1016/j.lddd.2025.100082","DOIUrl":"https://doi.org/10.1016/j.lddd.2025.100082","url":null,"abstract":"Ginsenoside Rh3 has been identified as an anti-cancer agent in colorectal cancer (CRC), and heat shock protein 90 alpha family class A member 1 (HSP90AA1) exhibits oncogenic function in CRC. This study explored the molecular mechanism of ginsenoside Rh3 associated with HSP90AA1 based on network pharmacology. Cell viability, proliferation, migration, invasion, apoptosis were measured through MTT, EdU, transwell and flow cytometry, respectively. Mitochondrial membrane potential and reactive oxygen species were detected to assess oxidative stress. The intersection targets between CRC and ginsenoside Rh3 were screened and protein-protein interaction (PPI) network was constructed, and then molecular docking between ginsenoside Rh3 and HSP90AA1 was performed. CRC cell proliferation and metastasis were repressed while apoptosis and oxidative stress were promoted by ginsenoside Rh3. Venn diagram showed 22 intersection targets, and PPI network analysis obtained top 10 and cluster 1 hub genes. Molecular docking revealed the high binding between ginsenoside Rh3 and HSP90AA1. Silencing HSP90AA1 suppressed CRC cell malignant progression. HSP90AA1 overexpression reversed anti-tumor effects of ginsenoside Rh3 on CRC cells. The obtained evidence explored the potential target of ginsenoside Rh3 through network pharmacology and molecular docking, and confirmed that ginsenoside Rh3 targeted HSP90AA1 to inhibit CRC cell development.","PeriodicalId":18059,"journal":{"name":"Letters in Drug Design & Discovery","volume":"22 6","pages":"100082-100082"},"PeriodicalIF":0.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147877463","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":"Imperatorin remits malignant progression of endometrial cancer by silencing E2F1/SLC3A2","authors":"Xuyan Huang, Fengyan Wang, Zhongyu Tang, Lina Dong, Xiaona Wang","doi":"10.1016/j.lddd.2025.100084","DOIUrl":"https://doi.org/10.1016/j.lddd.2025.100084","url":null,"abstract":"Endometrial cancer (EC) remains the most common gynecologic malignancy. Imperatorin (IMP), a bioactive natural furanocoumarin derivative, has demonstrated diverse pharmacological properties with particular promise in anti-tumor effects. Notably, the solute carrier family 3 member 2 (SLC3A2) is related to cancer cells. Concurrently, the transcription factor E2F transcription factor 1 (E2F1) plays a significant role in the progression of EC. This study aims to investigate the possible role of IMP and E2F1/SLC3A2 in EC progression and its underlying mechanism. The 3-(4,5-dimethyl-2-thiazolyl)−2,5-diphenyl-2-H-tetrazolium bromide (MTT), 5-ethynyl-2′-deoxyuridine (EdU), flow cytometry, transwell, and sphere formation assays were used to analyze the cell viability, proliferation, apoptosis, migration, and sphere-forming ability, respectively. The reactive oxygen species (ROS), ferrous iron (Fe 2+ ), and glutathione (GSH) levels were examined using corresponding detection kits. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blot were carried out to measure mRNA and protein levels. The binding relationship between E2F1 and the SLC3A2 promoter was predicted with the JASPAR website. The expression of E2F1 in Uterine Corpus Endometrial Carcinoma (UCEC) and its correlation with SLC3A2 were analyzed using the ENCOR database. A dual-luciferase reporter and chromatin immunoprecipitation (ChIP) were conducted to measure the interaction between E2F1 and SLC3A2. The in vivo EC models were constructed, and the tumor weight and volume were analyzed. The western blot and immunohistochemistry (IHC) were used to examine the E2F1 and SLC3A2 levels in vivo. IMP suppressed the EC cell viability in a concentration-dependent manner. Functionally, IMP hindered EC cell proliferation, invasion, and sphere-forming ability, as well as promoted cell apoptosis and ferroptosis. Notably, IMP repressed the SLC3A2 in HEC-1-B and RL95–2 cells. Up-regulated SLC3A2 could remit IMP-induced inhibition of EC cell malignant biological behavior. E2F1 facilitated the SLC3A2 expression. Interestingly, OE-SLC3A2 abolished si-E2F1-regulated inhibition of EC cell malignant behavior. OE-E2F1 could remit IMP-stimulated inhibition of EC cell malignant behavior. Additionally, in vivo, IMP repressed the EC tumor growth and levels of E2F1 and SLC3A2. IMP hinders the EC progression via silencing SLC3A2 and E2F1 levels. This finding suggests that IMP may be a potential novel therapeutic strategy for EC management. Imperatorin inhibits the malignant progression of EC by regulating SLC3A2/E2F1 in vitro and in vivo.","PeriodicalId":18059,"journal":{"name":"Letters in Drug Design & Discovery","volume":"22 6","pages":"100084-100084"},"PeriodicalIF":0.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147888101","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, molecular docking, and experimental validation of dihydromyricetin attenuating LPS-induced acute lung injury by promoting FGFR1","authors":"Qiming Chen, Sheng Liu, Wanting Song, Tianyu Lin, Yanyu Pan","doi":"10.1016/j.lddd.2025.100085","DOIUrl":"https://doi.org/10.1016/j.lddd.2025.100085","url":null,"abstract":"Acute lung injury (ALI) is a serious clinical condition characterized by severe lung inflammation, and its pathogenesis is complex. Dihydromyricetin (DHM) , a bioactive flavonoid component isolated from Ampelopsis grossedentata, is known for its anti-inflammatory effect; however, the role of DHM in ALI remains largely explored. The cell viability and apoptosis were analyzed using cell counting kit-8 (CCK8) and flow cytometry assays, respectively. The inflammation factors (tumor necrosis factor-alpha (TNF-α) and interleukin-1 beta (IL-1β)), reactive oxygen species (ROS), and superoxide dismutase (SOD) levels were examined using corresponding detection kits. Flow cytometry and quantitative real-time polymerase chain reaction (qRT-PCR) were used to detect M1 macrophage polarization. Besides, network pharmacology was conducted to present the molecular-interaction networks that were influenced by DHM in ALI, and molecular docking was used to predict the interaction between DHM and fibroblast growth factor receptor 1 (FGFR1). The gene and protein levels were examined using qRT-PCR and western blot. The ubiquitination of FGFR1 was analyzed using western blot. The ALI models in vivo were constructed to explore the action of DHM . Hematoxylin and eosin (HE) and Masson assays were used to detect lung tissue damage. The tissue cell apoptosis was detected using terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay. DHM abolished lipopolysaccharide (LPS)-induced BEAS-2B cell damage and the polarization of M1 macrophages. In addition, DHM facilitated FGFR1 expression via decreasing ubiquitination. LPS inhibited BEAS-2B cell viability and SOD and promoted cell apoptosis, inflammation factor production, ROS, and M1 macrophage polarization, but these actions were abolished by FGFR1. FGFR1 knockdown weakened DHM -induced alleviation action on LPS-stimulated BEAS-2B cell injury and polarization of M1 macrophages. In ALI models in vivo, DHM hindered LPS-induced ALI. Based on network pharmacology, molecular docking, and experimental verification, it is revealed that DHM remits LPS-induced ALI injury and M1 macrophage polarization through increasing FGFR1. This finding provides important molecular evidence for the further application of DHM in the clinical treatment of ALI.","PeriodicalId":18059,"journal":{"name":"Letters in Drug Design & Discovery","volume":"22 6","pages":"100085-100085"},"PeriodicalIF":0.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147893529","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":"Study on the effect of molecular regulation on oxaliplatin resistance and macrophage polarization in esophageal squamous cell carcinoma based on the multiomics bioinformatic analysis and experimental verification","authors":"Qiang Wang, Shiheng Ren, Pan Zheng, Yuxin Chen, Xiang‐Yan Liu","doi":"10.1016/j.lddd.2025.100061","DOIUrl":"https://doi.org/10.1016/j.lddd.2025.100061","url":null,"abstract":"Oxaliplatin (OHP) resistance remains a major therapeutic challenge in esophageal squamous cell carcinoma (ESCC). While Wnt1 inducible signaling pathway protein 1 (WISP1) has been implicated in tumor progression, its role in chemotherapy resistance and tumor microenvironment modulation remains unexplored in ESCC. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) to detect mRNA expression levels of WISP1. Western blotting was used to analyze protein expression of WISP1 and WT1 associated protein (WTAP). Cell viability, proliferation, apoptosis, migration, and invasion were assessed using cell counting kit-8 (CCK-8) assay, cell colony formation assay, flow cytometry, and transwell assays, respectively. The sensitivity of tumor cells to oxaliplatin (OHP) was evaluated by CCK-8 assay. The expression of CD11b and CD206-positive cells was quantified by flow cytometry. The interaction between WTAP and WISP1 was investigated using m 6 A RNA immunoprecipitation, RNA immunoprecipitation, and actinomycin D assays. WISP1 expression was upregulated in ESCC tissues and cells. Silencing WISP1 significantly improved OHP sensitivity and induced cell apoptosis, whereas inhibiting ESCC cell proliferation, migration, and invasion. Furthermore, WISP1 knockdown suppressed M2 macrophage polarization and inactivated the PI3K/AKT pathway. WTAP was shown to maintain the mRNA stability of WISP1 in KYSE-30 and KYSE-150 cells. Overexpression of WISP1 reversed the effects of WTAP knockdown on ESCC cell proliferation, migration, invasion, apoptosis, and OHP sensitivity. Additionally, WTAP knockdown inhibited M2 macrophage polarization by decreasing WISP1 expression. WTAP-induced stabilization of WISP1 inhibited OHP sensitivity and promoted the malignant progression of ESCC. These findings position WTAP-WISP1 as a promising therapeutic target for overcoming platinum resistance in esophageal cancer.","PeriodicalId":18059,"journal":{"name":"Letters in Drug Design & Discovery","volume":"22 5","pages":"100061-100061"},"PeriodicalIF":0.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147920881","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":"The inhibitory effects of Cucurbitacin B on hypopharyngeal cancer cell malignant behaviors were investigated based on network pharmacology and molecular docking","authors":"Xinjing Liu, Xiang Liu, Qiao Tong, Jing Lei, Man Wang","doi":"10.1016/j.lddd.2025.100066","DOIUrl":"https://doi.org/10.1016/j.lddd.2025.100066","url":null,"abstract":"Hypopharyngeal cancer is a metastatic squamous cell carcinoma of the head and neck (SCCHN), and the early symptoms are not obvious. Cucurbitacin B (Cu-B) is the most abundant member of the Cucurbitacin family and has a wide range of pharmacological activities, but its effect on hypopharyngeal cancer is not very clear. The cell functions were detected by the cell counting kit-8 (CCK-8), colony formation assay, 5-ethynyl-2′-deoxyuridine (EdU) staining, flow cytometry, wound healing, transwell, and tube formation assays. The Gene Expression Omnibus (GEO), Comparative Toxicogenomics Database (CTD), SwissTargetPrediction, and GeneCards databases were applied to identify the targets of Cu-B in hypopharyngeal cancer. What’s more, the protein-protein interaction (PPI) network was constructed using the String database, and the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed employing the DAVID database. The TOP 10 hub genes were screened adopting the Cytoscape software and the gene expression was predicted or determined by the GEO and Gene Expression Profiling Interactive Analysis (GEPIA) databases or quantitative reverse transcription PCR (qRT-PCR) and western blot. The molecular docking was executed in the Autodock Vina software. Cellular functional assays (cell counting kit-8 (CCK-8), colony formation, 5-ethynyl-2′-deoxyuridine (EdU) staining, flow cytometry, wound healing, transwell, and tube formation) were conducted. Network pharmacology integrating the Gene Expression Omnibus (GEO), Comparative Toxicogenomics Database (CTD), SwissTargetPrediction, and GeneCards databases identified potential Cu-B targets. Protein-protein interaction (PPI) network (String), Gene Ontology/Kyoto Encyclopedia of Genes and Genomes (GO/KEGG) enrichment analysis (DAVID), and molecular docking (Autodock Vina) were performed. Hub gene validation employed quantitative reverse transcription PCR (qRT-PCR), western blot, and rescue experiments. Cu-B dose-dependently restrained the malignant behaviors of FaDu cells. Bioinformatics analysis prioritized transforming growth factor beta 1 (TGFB1) as a core target, confirmed by its overexpression in hypopharyngeal cancer. Molecular docking revealed strong Cu-B-TGFB1 binding. Meanwhile, Cu-B retarded FaDu cell malignant behaviors by repressing TGFB1 expression. The network pharmacology along with bioinformatics analysis and molecular docking confirm that Cu-B may combine with TGFB1 to confine the malignant progression of hypopharyngeal cancer.","PeriodicalId":18059,"journal":{"name":"Letters in Drug Design & Discovery","volume":"22 5","pages":"100066-100066"},"PeriodicalIF":0.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147898116","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 molecular docking to explore the potential mechanism of Congerjingming Decoction against sensorineural hearing loss","authors":"Wenhui Hu, Qingchang Xing","doi":"10.1016/j.lddd.2025.100046","DOIUrl":"https://doi.org/10.1016/j.lddd.2025.100046","url":null,"abstract":"Established formulations of traditional Chinese medicine (TCM) have shown efficacy in the management of age-related sensorineural hearing loss (SNHL). In this study, we developed a novel TCM, Congerjingming Decoction (CD), and explored the mechanism of CD in treating SNHL. TCMSP and Swiss Target Prediction databases were used to collect potential targets of corresponding chemicals of CD. The molecular targets implicated in SNHL were searched using GeneCards. A drug-compound-target-disease network was constructed using Cytoscape software. The protein-protein interaction (PPI) network analysis was performed using STRING database. The GO and KEGG pathway enrichment analyses were conducted using DAVID platform. Molecular docking was performed using AutoDock vina program and visualized with Pymol software. A total of 277 potential targets of CD, 4497 candidate targets associated with SNHL, and 136 CD-SNHL intersection targets were identified. AKT1, TNF, TP53, and CASP3 were identified as hub targets of CD against SNHL. Apigenin, kaempferol, and puerarin were the top three ranked active components of CD. These intersection targets were associated with the regulation of apoptosis and cell cycle and the p53, PI3K-Akt, and HIF-1 signaling pathways. Apigenin, kaempferol, and puerarin exhibited strong binding affinities to AKT1, TNF, and CASP3, with interactions driven by hydrophobic forces and hydrogen bonds. Moreover, CD could protect against cisplatin (CP)-induced viability impairment in HEI-OC1 cells. Our findings suggest that multiple components of CD may work through various targets and pathways in treating SNHL, providing a foundation for further investigation of the pharmacological mechanisms of CD against SNHL.","PeriodicalId":18059,"journal":{"name":"Letters in Drug Design & Discovery","volume":"22 4","pages":"100046-100046"},"PeriodicalIF":0.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147916834","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":"The mechanisms of Mahuang decoction in treating COPD: Insights from network pharmacology and in vivo studies","authors":"Quan Qiu, Yaya Guo, Liangping Li, Feng Sang, Li‐Yan Xu","doi":"10.1016/j.lddd.2025.100048","DOIUrl":"https://doi.org/10.1016/j.lddd.2025.100048","url":null,"abstract":"Chronic obstructive pulmonary disease (COPD) is a major cause of significant mortality worldwide. Mahuang decoction (MHD), a classic traditional Chinese medicine, has demonstrated encouraging therapeutic potential for COPD due to its multiple pharmacological properties, including anti-inflammatory activity. However, its underlying mechanisms remain unclear. The purpose of this study was to investigate the mechanisms underlying MHD's efficacy against COPD. The bioactive ingredients of MHD and the corresponding candidate targets, the potential factors related to COPD, and their shared candidate targets were identified. A protein-protein interaction (PPI) network of the shared targets and an MHD compound-target-COPD network were constructed. Gene ontology (GO) and kyoto encyclopedia of genes and genomes (KEGG) enrichment analyses were performed to observe biological functions. An in vivo rat model of COPD was established by cigarette smoke exposure and lipopolysaccharide (LPS) endotracheal instillation and subjected to MHD administration. Tumor necrosis factor alpha (TNF-α), interleukin 6 (IL-6) and IL-1β levels were detected by enzyme-linked immunosorbent assay. The number of apoptotic cells was assessed by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining. Malondialdehyde (MDA), superoxide dismutase (SOD), and catalase (CAT) levels were analyzed using the assay kits. The mRNA levels of akt serine/threonine kinase 1 (AKT1), TNF-α, IL-6, and IL-1β were detected by quantitative polymerase chain reaction (PCR). The protein levels of b-cell lymphoma 2 (BCL2), BCL2-associated x protein (BAX), cleaved-Caspase-3, TNF-α, TNF receptor 1 (TNFR1), phosphorylated nuclear factor kappa b (p-NF-κB) p65, and phosphorylated inhibitor of kappa b alpha (p-IκBα) were assessed by immunoblotting. This study identified 54 active components and 173 candidate targets of MHD, 1224 putative targets associated with COPD, and 110 shared targets. PPI analysis revealed the top 12 core candidate targets (e.g., AKT1, TNF, IL-6, and IL-1β) for MHD's efficacy in COPD treatment. Various components (e.g., quercetin, luteolin, and isorhamnetin) were identified as the main active ingredients in MHD for COPD treatment. GO enrichment analysis showed that these shared targets were closely correlated with response to xenobiotic stimuli and cellular response to LPS. KEGG enrichment analysis showed the potential implication of TNF-α pathway in MHD's efficacy against COPD. In COPD rats, MHD diminished lung pathological injury and reduced TNF-α, IL-6, and IL-1β levels in the BALF. Moreover, MHD reduced MDA amount, elevated SOD and CAT levels, decreased the mRNA expression of AKT1, TNF-α, IL-6, and IL-1β, diminished the percentage of TUNEL-positive cells, increased BCL2 expression, and reduced BAX and cleaved-Caspase-3 levels in lung tissues of COPD rats. Furthermore, MHD inactivated the TNF-α/NF-κB pathway in COPD rats. Our study shows that MHD alleviates COPD by tar","PeriodicalId":18059,"journal":{"name":"Letters in Drug Design & Discovery","volume":"22 4","pages":"100048-100048"},"PeriodicalIF":0.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147922958","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":"Epigallocatechin gallate impels osteogenic differentiation of human BMSCs by targeting the METTL3/SATB2/Wnt/β-catenin axis","authors":"Qiao Ren, Kang Chen, Lin Wang","doi":"10.1016/j.lddd.2025.100027","DOIUrl":"https://doi.org/10.1016/j.lddd.2025.100027","url":null,"abstract":"Bone marrow mesenchymal stem cells (BMSCs) are pluripotent cell, and its osteogenic differentiation disorder can lead to osteoporosis and seriously affect the quality of life. Epigallocatechin gallate (EGCG) is a catechin that has not been thoroughly studied on BMSCs. Flow cytometry was used for detecting cell surface antigens to identify BMSCs. Cell viability was measured using cell counting kit-8 (CCK8). Alkaline phosphatase (ALP) and alizarin red s (ARS) staining were employed for analyzing osteogenic differentiation. The expression of related genes was examined by western blot and quantitative real-time PCR (qRT-PCR). For the study of mechanism, ENCORI database, SRAMP database, methylated RNA immunoprecipitation (MeRIP), RNA immunoprecipitation (RIP) and mRNA stability assay were utilized to predict and validate the interactions between the proteins. EGCG enhanced cell viability and osteogenic differentiation of BMSCs. Moreover, special AT-rich sequence-binding protein 2 (SATB2) knockdown reversed the effect of EGCG in BMSCs. Mechanically, methyltransferase 3 (METTL3) mediated the N 6 -methyladenosine (m6A) methylation of SATB2. -Furthermore, EGCG-mediated promotion on BMSCs was weakened with the absence of METTL3. In addition, the deficiency of METTL3 and SATB2 could -abolish the effect of EGCG on Wnt/β-catenin pathway. EGCG induced osteogenic differentiation of BMSCs by affecting the METTL3/SATB2-mediated Wnt/β-catenin pathway.","PeriodicalId":18059,"journal":{"name":"Letters in Drug Design & Discovery","volume":"22 3","pages":"100027-100027"},"PeriodicalIF":0.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147922149","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}