Letters in Drug Design & Discovery最新文献

{"title":"Exploring the mechanism of Grifolin in inhibiting the malignant progression of colon cancer cells mediated by the PDGFRB/PI3K/AKT signaling pathway based on bioinformatics analysis and network pharmacology","authors":"Yu Han, Yaping Chen, Xiao Xu, Zhong Li, Wentai Shi, Qiling Lin","doi":"10.1016/j.lddd.2025.100018","DOIUrl":"https://doi.org/10.1016/j.lddd.2025.100018","url":null,"abstract":"Colon cancer is one of the most common malignant tumors worldwide, which seriously threatens human life and health. Grifolin is a small molecule compound that has been shown to inhibit the malignant progression of a variety of cancers. The aim of this study is to investigate the mechanism of Grifolin in the treatment of colon cancer based on bioinformatics and network pharmacology. The effects of Grifolin on the proliferation, apoptosis, migration, invasion and glycolysis of colon cancer cells were examined by CCK-8, colony formation, EdU, flow cytometry, wound healing, Transwell, and corresponding kits. The differentially expressed genes in colon cancer and the target genes of Grifolin and colon cancer were analyzed by GEO database, CTD, SwissTarget, and GeneCards websites, and the PPI network was constructed by the STRING website to screen the common targets. GO and KEGG enrichment analysis was performed on the common targets. The PI3K/AKT pathway-related proteins were measured by western blot. Grifolin could block the viability and proliferation, but induce apoptosis of colon cancer cells. It also retarded the migration, invasion, and glycolysis. GO and KEGG analysis indicated that the target genes of Grifolin in the treatment of colon cancer had transmembrane transporter tyrosine kinase activity and were related to the PI3K-AKT signaling pathway and central carbon metabolism. Additionally, Grifolin was confirmed to downregulate the PDGFRB, PI3K, p-AKT, BCL-2 and GLUT1 protein levels. Grifolin curbed the malignant progression of colon cancer cells by interfering with glycolysis and the PI3K/AKT signaling pathway.","PeriodicalId":18059,"journal":{"name":"Letters in Drug Design & Discovery","volume":"22 2","pages":"100018-100018"},"PeriodicalIF":0.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147903951","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":"Puerarin alleviates spinal cord injury by mediating the proliferation and activation of NG2 glial cells","authors":"Ping Ye, Xinyuan Liao, Yin Zhao, Shengyuan Zhou, Xiang Guo, Lili Yang, Bitao Lv","doi":"10.1016/j.lddd.2025.100011","DOIUrl":"https://doi.org/10.1016/j.lddd.2025.100011","url":null,"abstract":"Spinal cord injury (SCI) leads to significant brain alterations, the vital factors affecting functional recovery. Accumulating evidence demonstrated the neuroprotective effect of Puerarin (Pur), a natural extract, in a rat model of SCI. The study is designed to explore the role and mechanism of Pur on SCI. A total of 24 rats were divided into 2 groups: sham group and SCI group. 9 rats were used for in vitro experiments, where NG2 cells were extracted from both groups, and NG2 cells from the SCI group were treated with Pur. EdU, western blotting, and ELISA were utilized to detect effects of Pur on NG2 cell proliferation, differentiation and inflammation after SCI. Another 15 rats were utilized for in vivo experiment and the SCI group was given Pur treatment for subsequent assays. Locomotor function was evaluated using the BBB test. The histological changes in the spinal cord were observed by HE and Nissl staining. Neuron survival and glial cell activation were evaluated by western blotting and ELISA. Based on network pharmacology, the corresponding targets of Pur and SCI were collected from TCMSP, SwissTargetPrediction Database, GeneCards Database. The protein-protein interaction (PPI) networks of intersected targets were constructed by using the STRING database and visualized using Cytoscape. GO enrichment and KEGG pathway enrichment analyses were conducted to assess the function of the intersection target. AutoDockTools and PyMOL were used for molecular docking to recognize the association between the core ingredients of Pur and the core target of SCI. Casp3, Bcl2, and Pparg mRNA levels were detected using real-time quantitative polymerase chain reaction (RT-qPCR). Pur ameliorated SCI-induced NG2 cell proliferation and inflammation in vitro . Moreover, Pur increased BBB score in SCI rats, relieved histological injury, decreased neuron loss, repressed gliall cell activation, and alleviated inflammation in the injured spinal cords. From 33 candidate target genes of Pur and SCI, the PPI network identified ten hub genes. GO and KEGG analysis indicated that the target gene Casp3, Bcl2, and Pparg was mostly enriched in SCI. The molecular docking results displayed that the core ingredients of Pur had good binding ability with Casp3, Bcl2, and Pparg. Casp3, Bcl2 mRNA levels were decreased in the SCI group, and Pparg was increased. Pur could abolish SCI by regulating Casp3, Bcl2, and Pparg, which might provide novel ideas for the therapy of SCI.","PeriodicalId":18059,"journal":{"name":"Letters in Drug Design & Discovery","volume":"22 2","pages":"100011-100011"},"PeriodicalIF":0.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147891178","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":"Thymoquinone suppresses cell growth and induces ferroptosis in renal cell carcinoma by reducing SERPINH1 expression","authors":"Ruiying Luo, Shuang Li, Haohao Wang, Zuyu Zhang, Long Li, Panfeng Shang","doi":"10.1016/j.lddd.2025.100013","DOIUrl":"https://doi.org/10.1016/j.lddd.2025.100013","url":null,"abstract":"Thymoquinone (TQ) plays an important role in regulating cell behaviors of renal cell carcinoma (RCC). Ferroptosis is an iron-dependent cell death involving in cancer repression. Herein, the effect of TQ on ferroptosis and its association with serpin family H member 1 (SERPINH1) were investigated. Real-time quantitative PCR and western blot were adopted for mRNA and protein detection. Cell growth was assessed by cell counting kit-8 and colony formation assays. Flow cytometry was performed for apoptosis examination. Transwell assay was used to measure cell migration and invasion. Reactive oxygen species (ROS), glutathione (GSH), and Fe 2+ were determined by the corresponding kits. SERPINH1 was an up-regulated gene in RCC. Silence of SERPINH1 blocked RCC cell growth, migration and invasion but induced apoptosis and ferroptosis. TQ could target SERPINH1 and down-regulated the expression of SERPINH1. TQ suppressed cell viability and facilitated ferroptosis, which was attributed to level inhibition of SERPINH1. These results disclosed that TQ acted on SERPINH1 to down-regulate its expression, consequently hindering cell progression and motivating ferroptosis in RCC. SERPINH1 may be a biological marker in the treatment of TQ for RCC by targeting ferroptosis.","PeriodicalId":18059,"journal":{"name":"Letters in Drug Design & Discovery","volume":"22 2","pages":"100013-100013"},"PeriodicalIF":0.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147908014","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 Pharmacological Analysis and Experimental Validation of Anti-lung Cancer Effect of Echinacea Purpurea","authors":"Shengming Ma, Chiwen Mao, Shaoting Weng, Zhihui Jiang, Hao Jie, Kunpeng Zhang","doi":"10.2174/0115701808354108250123115558","DOIUrl":"https://doi.org/10.2174/0115701808354108250123115558","url":null,"abstract":"","PeriodicalId":18059,"journal":{"name":"Letters in Drug Design & Discovery","volume":"22 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147893179","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Efficacy of Oxysophocarpine in Treating Cerebral Ischemia: Integration of Network Pharmacology and Experimental Validation","authors":"Zhihua Wang, Haiqi Qiao, Yang Yu, Siyun Liu, Fang Zhao, Ru Zhou","doi":"10.2174/0115701808359027250105180011","DOIUrl":"https://doi.org/10.2174/0115701808359027250105180011","url":null,"abstract":"","PeriodicalId":18059,"journal":{"name":"Letters in Drug Design & Discovery","volume":"22 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147877696","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Emerging Novel Role of Metformin in Decreasing Post-surgical Adhesion Band Formation","authors":"Seyedeh Elnaz Nazari, Elnaz Ghorbani, Abdulridha Mohammed Al-Asady, Sayyed-Hadi Sayyed-Hosseinian, Ehsan Vahedi, Moein Eskandari, Mohammad-Mostafa Askarnia-Faal, Hamideh Naimi, Fereshteh Asgharzadeh, Amir Avan, Saeide Mansoori, Mikhail Ryzhikov, Majid Khazaei, Majid Khazaei, Seyed Mahdi Hassanian","doi":"10.2174/0115701808330601241217101809","DOIUrl":"https://doi.org/10.2174/0115701808330601241217101809","url":null,"abstract":"","PeriodicalId":18059,"journal":{"name":"Letters in Drug Design & Discovery","volume":"21 18","pages":"4520-4528"},"PeriodicalIF":0.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147919516","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Enhancing Renal Autophagy via Yangshen Paidu Decoction: AMPK/mTOR Pathway Modulation in Chronic Renal Failure Management","authors":"Hao-xun Tang, Qi T, Yifan Li, Xiaohui Bai, Dan Lv, Fang Wang, Ronghua Pan, Yanmei Zhao","doi":"10.2174/0115701808331134241128053200","DOIUrl":"https://doi.org/10.2174/0115701808331134241128053200","url":null,"abstract":"Objective: Chronic Renal Failure (CRF) refers to the gradual decline in renal function caused by various chronic kidney diseases, eventually leading to end-stage renal failure. Yangshen Paidu Decoction (YPD) is a Traditional Chinese medicine (TCM) formula utilized in CRF treatment. This work has analyzed the effects of YPD on CRF and the specific mechanism. Methods: Network pharmacology was performed to screen effective components and targets of YPD, from which key targets and signaling pathways contributing the most to the treatment effects on CRF were determined. Subsequently, we validated the therapeutic role of YPD and the underlying pathological mechanisms using the 5/6-nephrectomy rat model. Results: Network pharmacology analysis showed the mTOR pathway to be a pivotal mechanism underlying the effectiveness of YPD in CRF treatment. YPD significantly suppressed urine protein levels, blood urea nitrogen, and serum creatinine in 5/6 nephrectomized rats. Furthermore, YPD remarkably improved renal pathological injuries. Western blot analysis revealed that YPD enhanced autophagy and upregulated the expression of nephrin, podocin, beclin1, p-AMPK/AMPK, and p- ULK1/ULK1, and attenuated the ratios of p-mTOR/mTOR to its downstream protein phosphorylated eIF4E-binding protein (p-4EBP1). However, these effects were notably reversed by the AMPK inhibitor compound C. Conclusion: Our findings have demonstrated YPD to suppress the mTOR pathway and stimulate autophagy by modulating AMPK pathways, thereby mitigating podocyte injury and enhancing renal function. Our study has confirmed autophagy and the AMPK/mTOR pathway as potential targets for YPD in CRF treatment.","PeriodicalId":18059,"journal":{"name":"Letters in Drug Design & Discovery","volume":"21 18","pages":"4465-4477"},"PeriodicalIF":0.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147897170","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":"Lidocaine Induces Neurotoxicity by Activating the CaMKII and p38 MAPK Signaling Pathways through an Increase in Intracellular Calcium Ions","authors":"Qian Ma, Meng Wang, Bin Zhang, Danting Jia, Xue‐Xin Chen","doi":"10.2174/0115701808355819241118115155","DOIUrl":"https://doi.org/10.2174/0115701808355819241118115155","url":null,"abstract":"","PeriodicalId":18059,"journal":{"name":"Letters in Drug Design & Discovery","volume":"21 18","pages":"4418-4428"},"PeriodicalIF":0.0,"publicationDate":"2024-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147902370","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mechanism of Trigonella Foenum-graecum L. against Type 2 Diabetes Mellitus: Research on Network Pharmacology & Experimental Verification","authors":"Wenya Liu, Hongting Ma, Jun Luo, Yanfeng He","doi":"10.2174/0115701808304547240911105921","DOIUrl":"https://doi.org/10.2174/0115701808304547240911105921","url":null,"abstract":"","PeriodicalId":18059,"journal":{"name":"Letters in Drug Design & Discovery","volume":"21 17","pages":"4072-4084"},"PeriodicalIF":0.0,"publicationDate":"2024-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147879190","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Structural Optimization of Quinazolin-4-One Derivatives as Novel SARS-CoV-2 Mpro Inhibitors by Molecular Simulation","authors":"Jinping Wu, Peng Li, Yucheng Mu, Ruiguang Peng, Zhongyao Zhao, Jinke Lei, Aiping Tu, Zhiting Gao, Yixiao Bai, Gang Wu","doi":"10.2174/0115701808330125240812104856","DOIUrl":"https://doi.org/10.2174/0115701808330125240812104856","url":null,"abstract":"Background: Severe acute respiratory syndrome coronavirus 2 main protease (SARSCoV- 2 Mpro) has been shown to be an effective target for inhibiting novel coronaviruses, which can be used as a crucial breakthrough for developing drugs to treat the coronavirus disease 2019 (COVID-19). Methods: To design novel SARS-CoV-2 Mpro inhibitors, we conducted 3D-QSAR, molecular docking, and molecular dynamics (MD) simulation on 64 quinazolin-4-one derivatives. Results: Comparative molecular field analysis (CoMFA) model (q2 = 0.590, R2 = 0.962), comparative molecular similarity index analysis (CoMSIA) model (q2 = 0.628, R2 = 0.923), and external validation indicated that the stability, reliability, and prediction performance of our constructed model were excellent. We designed 8 inhibitors with stronger antiviral activities through the three-dimensional equipotential field. Molecular docking and MD simulation probed the interactions of compounds and SARS-CoV-2 Mpro. This indicated that amino acid residues, including Met165, Met49, and Cys145, were very important in combination with the compounds. The prediction results of ADME/T and Lipinski’s rule of five indicated that the new compounds had favorable drug-like and pharmacokinetic properties. Conclusion: This study provides new ideas for exploring new drugs against COVID-19","PeriodicalId":18059,"journal":{"name":"Letters in Drug Design & Discovery","volume":"47 1","pages":""},"PeriodicalIF":1.0,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142192106","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}