Drug Design, Development and Therapy最新文献

{"title":"Caffeic Acid Protects Against Ulcerative Colitis via Inhibiting Mitochondrial Apoptosis and Immune Overactivation in <i>Drosophila</i>.","authors":"Minghui Xiu, Botong Li, Li He, Yan Shi, Yongxuan Zhang, Shihong Zhou, Yongqi Liu, Ningbo Wang, Jianzheng He","doi":"10.2147/DDDT.S499284","DOIUrl":"10.2147/DDDT.S499284","url":null,"abstract":"<p><strong>Background: </strong>Ulcerative colitis (UC) is a chronic intestinal inflammation that is prone to relapse and is difficult to fully recover; therefore, there is a need for safer alternative treatments. Caffeic acid (CA) is a natural polyphenolic compound that has antioxidant and anti-inflammatory properties. However, the beneficial effects and mechanisms of action of CA in UC remain unclear.</p><p><strong>Purpose: </strong>This study evaluated the protective effect of CA against dextran sulfate sodium (DSS)-induced intestinal injury in <i>Drosophila</i> melanogaster model.</p><p><strong>Results: </strong>Oral administration of CA significantly reduced body damage in UC flies, improved their survival rate, restored damaged digestion, and improved locomotion. CA supplementation significantly alleviated intestinal damage in UC flies by restoring excretion balance, repairing intestinal atrophy, improving acid-base balance imbalance, inhibiting intestinal structural destruction, inhibiting intestinal epithelial cell death and intestinal stem cell (ISC) excessive proliferation, and reducing the number of harmful bacteria. Mechanistic studies found that CA significantly reduced the expression of Toll and Imd pathway genes (including <i>Myd88, Dif, PGRP-LC, Imd, Rel</i>, and <i>Dpt</i>), reduced ROS levels and the expression of apoptosis-related genes (<i>Debcl, Cyt-c-p, DrlCE, Dronc</i>, and <i>Dark</i>), and increased ATP and MFN2 levels.</p><p><strong>Conclusion: </strong>CA alleviated intestinal damage mainly by inhibiting the Toll and Imd signaling pathways and inhibiting apoptosis mediated by mitochondrial damage. These findings suggest that CA holds promise as a potential therapeutic for UC treatment.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"2157-2172"},"PeriodicalIF":4.7,"publicationDate":"2025-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11938933/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143718323","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unveiling the Therapeutic Potential of Banxia Xiexin Decoction in Alzheimer's Disease: Insights From Network Pharmacology and Experimental Validation.","authors":"Gaofeng Qin, Rongqiang Song, Jingyi Sun, Juanjuan Dai, Wentao Wang, Fantao Meng, Dan Wang, Zhe Liu, Baoliang Sun, Chen Li","doi":"10.2147/DDDT.S499852","DOIUrl":"10.2147/DDDT.S499852","url":null,"abstract":"<p><strong>Background: </strong>Alzheimer's disease (AD) is associated with various pathological states for which there is no effective treatment. First documented in the Eastern Han Dynasty's medical classic, \"Treatise on Febrile and Miscellaneous Diseases\" (200-210 Anno Domini), Banxia Xiexin Decoction (BXD) stands as a quintessential approach to treating spleen ailments. Recent studies have shown BXD's effectiveness in mitigating memory impairment associated with AD. Yet, the precise mechanisms underlying BXD's action against AD require further exploration.</p><p><strong>Aim of the study: </strong>To explore the important components of BXD in exerting anti-AD effects and the underlying molecular mechanisms using network pharmacology, metabolomics analysis, and in vitro and in vivo validation strategies. Initially, candidates for BXD's application in AD therapy were identified through extensive database searches, followed by an analysis of protein-protein interactions (PPI). To elucidate BXD's therapeutic pathways in AD, we engaged in Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) assessments. Further, we delved into BXD's primary constituents through ultra-high-pressure liquid chromatography coupled with Q Exactive mass spectrometry and molecular docking techniques. Finally, AD-associated Aβ₄₂-SY5Y cells and APPswe/PS1dE9 (APP/PS1) transgenic mice models were utilized to further determine the activity and mechanisms of BXD through various molecular or phenotypic assays and metabolomics analysis.</p><p><strong>Results: </strong>Our findings identified the PI3K/Akt signaling pathways as central to BXD's effects. Using in vitro and in vivo models, we found the activity of BXD against AD to be mediated by the suppression of neuroinflammation and apoptosis, accompanied by activation of the PI3K/Akt pathway. Finally, we observed robust changes in metabolite levels in the plasma of BXD-treated APP/PS1 mice.</p><p><strong>Conclusion: </strong>Through systematic data analysis and experimental validation, the therapeutic advantages and fundamental molecular mechanisms of BXD in treating AD were revealed. These findings underscore the promising prospects and compelling potential of BXD, which targets the PI3K/Akt signaling pathway and inflammation, apoptosis, as a therapeutic strategy for improving AD.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"2133-2155"},"PeriodicalIF":4.7,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11934878/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143708439","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Erratum: Population Pharmacokinetic of Epidural Sufentanil in Labouring Women: A Multicentric, Prospective, Observational Study [Corrigendum].","authors":"","doi":"10.2147/DDDT.S528296","DOIUrl":"https://doi.org/10.2147/DDDT.S528296","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.2147/DDDT.S500189.].</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"2131-2132"},"PeriodicalIF":4.7,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11933922/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143708213","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Deciphering the Pharmacological Potential of Kouqiangjie Formula for the Treatment of Diabetic Periodontitis Based on Network Pharmacology, Machine Learning, Molecular Dynamics, and Animal Experiments.","authors":"Yeke Wu, Jiawei Li, Min Liu, Ranran Gao, Huijing Li, Yunfei Xie, Qiongying Hu, Jing Wei, Lixing Zhao, Li Li","doi":"10.2147/DDDT.S494066","DOIUrl":"10.2147/DDDT.S494066","url":null,"abstract":"<p><strong>Background: </strong>Periodontitis (PD) and type 2 diabetes mellitus (T2DM) represent interlinked global health burdens, commonly causing significant clinical complications when coincident. Therefore, managing both conditions (T2DM with periodontitis, DP) simultaneously poses considerable challenges, necessitating novel therapeutic strategies. KQJF has been clinically proven to treat DP with good efficacy, but its pharmacological substances and targets are not clear and urgently need to be clarified.</p><p><strong>Aim: </strong>To define the potential active components and targets of KQJF for the treatment of DP.</p><p><strong>Materials and methods: </strong>The investigation commenced with the application of UPLC-Q-TOF/MS analysis to delineate the active constituents of KQJF and their associated targets in addressing DP. Additionally, the research incorporated subsequent methodologies such as machine learning, network pharmacology, molecular docking, molecular dynamics simulations, and a DP rat model was established and validated by in vivo experiments using H&E staining, immunohistochemistry, quantitative real-time PCR, and Western blot.</p><p><strong>Results: </strong>KQJF was found to contain 49 prototype compounds and 121 metabolites with potential activity against PD and T2DM. Network pharmacology revealed 66 overlapping genes between the pharmacological targets of KQJF and known targets of PD and T2DM. Further exploration through PPI network and enrichment analyses illuminated the involvement of multi-target and multi-pathway mechanisms. Molecular docking and dynamics simulations confirmed the robust interactions between key compounds within KQJF and proteins associated with the diseases. In vivo validation demonstrated that KQJF treatment ameliorated DP-associated histopathological changes and modulated the expression of crucial proteins (including ABCG2, CCND1, CDKN1B, HIF1A, and PIK3R1) in a DP rat model.</p><p><strong>Conclusion: </strong>In summary, KQJF exhibits potential therapeutic benefits for DP through a multi-component and multi-target approach, potentially offering a novel integrative treatment strategy. This study underscores the importance of integrating traditional medicine with modern molecular techniques to explore novel therapeutic avenues for complex comorbid conditions, providing a blueprint for future pharmacological explorations.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"2103-2129"},"PeriodicalIF":4.7,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11932940/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143709172","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mannosamine-Engineered Nanoparticles for Precision Rifapentine Delivery to Macrophages: Advancing Targeted Therapy Against Mycobacterium Tuberculosis.","authors":"Haopeng Luan, Cong Peng, Parhat Yasin, Qisong Shang, Wei Xiang, Xinghua Song","doi":"10.2147/DDDT.S505682","DOIUrl":"10.2147/DDDT.S505682","url":null,"abstract":"<p><strong>Background: </strong>Tuberculosis, caused by Mycobacterium tuberculosis (Mtb), remains one of the leading causes of death among infectious diseases. Enhancing the ability of anti-tuberculosis drugs to eradicate Mycobacterium tuberculosis within host cells remains a significant challenge.</p><p><strong>Methods: </strong>A mannosamine-modified nanoparticle delivery system was developed using poly(lactic-co-glycolic acid) (PLGA) copolymers to enhance the targeted delivery of rifapentine (RPT) to macrophages. D-mannosamine was conjugated to PLGA-polyethylene glycol (PLGA-PEG) copolymers through EDC/NHS coupling chemistry, and the resultant RPT-MAN-PLGA-PEG nanoparticles (NPs) were prepared through a combination of phacoemulsification and solvent evaporation methods. The physicochemical properties, toxicity, in vitro drug release profiles, stability, cellular uptake, and anti-TB efficacy of the NPs were systematically evaluated.</p><p><strong>Results: </strong>The RPT-MAN-PLGA-PEG NPs had a mean particle size of 108.2 ± 7.2 nm, with encapsulation efficiency and drug loading rates of 81.2 ± 6.3% and 13.7 ± 0.7%, respectively. RPT release from the NPs was sustained for over 60 hours. Notably, the phagocytic uptake of the MAN-PLGA NPs by macrophages was significantly higher compared to PLGA-PEG NPs. Both NPs improved pharmacokinetic parameters without inducing significant organ toxicity. The minimum inhibitory concentration for the NPs was 0.047 μg/mL, compared to 0.2 μg/mL for free RPT.</p><p><strong>Conclusion: </strong>The engineered RPT-MAN-PLGA-PEG NPs effectively enhanced macrophage uptake in vitro and facilitated the intracellular clearance of Mtb. This nanoparticle-based delivery system offers a promising approach for improving the precision of anti-TB therapy, extending drug release, optimizing pharmacokinetic profiles, augmenting antimicrobial efficacy, and mitigating drug-related toxicities.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"2081-2102"},"PeriodicalIF":4.7,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11931292/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143699985","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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 Validation Reveal Sishen Pill's Efficacy in Treating NSAID-Induced Small Intestinal Ulcers.","authors":"Jiaying Zhou, Fengting Zhu, Huixian Liang, Leimin Sun","doi":"10.2147/DDDT.S502193","DOIUrl":"10.2147/DDDT.S502193","url":null,"abstract":"<p><strong>Purpose: </strong>Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used but often cause small intestinal ulcers (SIUs), for which effective therapies are lacking. Sishen Pill (SSP), a traditional Chinese medicine, shows therapeutic promise, yet its mechanisms remain unclear. This study integrates network pharmacology, molecular docking, and experimental validation to systematically investigate SSP's protective mechanisms against NSAID-induced SIUs.</p><p><strong>Patients and methods: </strong>Active SSP ingredients were screened using the Traditional Chinese Medicine Systems Pharmacology (TCMSP) and Encyclopedia of Traditional Chinese Medicine (ETCM) databases. SIU-related targets were retrieved from GeneCards and DisGeNET. Protein-protein interaction (PPI) networks were constructed via STRING and Cytoscape, followed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. Molecular docking (AutoDock Vina, PyMOL) validated ligand-target interactions. In vivo validation employed an indomethacin-induced SIU rat model to assess SSP's effects on ulcer severity, inflammation, oxidative stress, and PI3K/AKT signaling.</p><p><strong>Results: </strong>We identified 66 bioactive SSP ingredients, 222 drug targets, and 144 SIU-related targets. Molecular docking revealed high binding affinity of SSP components (quercetin, bavachinin, rutaecarpine, evodiamine) to key targets (AKT1, HSP90AA1, IL6, MAPK1, BCL2). KEGG analysis highlighted the PI3K/AKT pathway as central. In vivo, SSP reduced ulcer indices, suppressed pro-inflammatory cytokines (TNF-α, IL-1β, IL-6), and attenuated oxidative stress. SSP also downregulated PI3K and AKT1 mRNA expression, confirming pathway modulation.</p><p><strong>Conclusion: </strong>This study elucidates SSP's multi-target mechanism against NSAID-induced SIUs, emphasizing its role in suppressing inflammation, oxidative stress, and PI3K/AKT signaling. These findings provide a scientific foundation for SSP's clinical application and highlight its potential as a safe, effective alternative to conventional therapies.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"2035-2050"},"PeriodicalIF":4.7,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11930021/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143691205","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Novel AP39-Loaded Liposomes Sustain the Release of Hydrogen Sulphide, Enhance Blood-Brain Barrier Permeation, and Abrogate Oxidative Stress-Induced Mitochondrial Dysfunction in Brain Cells.","authors":"Mohamad Anas Al Tahan, Mandeep Kaur Marwah, Mandheer Dhaliwal, Lorena Diaz Sanchez, Hala Shokr, Manjit Kaur, Shakil Ahmad, Raj K S Badhan, Irundika H K Dias, Lissette Sanchez-Aranguren","doi":"10.2147/DDDT.S507697","DOIUrl":"10.2147/DDDT.S507697","url":null,"abstract":"<p><strong>Background: </strong>Neurodegenerative diseases are often linked to oxidative stress (OS), which worsen neuroinflammation and cause neuronal damage. Managing OS with gasotransmitters such as hydrogen sulphide (H₂S) is a promising therapeutic approach to protecting brain cells from oxidative damage. AP39, a mitochondria-targeted H₂S donor, has shown neuroprotective potential by reducing OS and improving mitochondrial function. However, its clinical application is limited due to poor stability and rapid release, necessitating a drug delivery system to enhance therapeutic efficacy.</p><p><strong>Purpose: </strong>This study aimed to develop a novel AP39-loaded liposomal formulation to provide controlled H₂S release, facilitate AP39 permeation across the blood-brain barrier (BBB), and assess functional effects in mitigating oxidative stress and preserving mitochondrial function.</p><p><strong>Methods: </strong>AP39-loaded unilamellar liposomes were prepared via ethanol injection and characterised for size, polydispersity, and zeta potential. Entrapment efficiency was determined using HPLC, while cytotoxicity was assessed in human vein endothelial (HUVEC) and neuroblastoma (SHSY5Y) cells. Liposomal permeability, AP39 release kinetics, and cellular uptake were evaluated using a microvasculature BBB model. Mitochondrial function under oxidative stress was assessed using a Seahorse XFe24 Analyzer.</p><p><strong>Results: </strong>AP39-loaded liposomes had an average size of 135.92 ± 10.05 nm, a zeta potential of 17.35 ± 3.40 mV, and an entrapment efficiency of 84.48% ± 4.7. Cytotoxicity studies showed no adverse effects after 4 h. Cellular uptake of encapsulated AP39 was significantly higher (7.13 ± 0.28 µg) than the free form (5.8 ± 0.31 µg). The BBB model demonstrated sustained AP39 release (7.28 µg/mL vs 6.44 µg/mL for free AP39). Mitochondrial assays confirmed liposomal AP39 preserved H₂S antioxidant properties and enhanced oxygen consumption.</p><p><strong>Conclusion: </strong>Our novel liposomal formulation encapsulating AP39 improves stability, promotes sustained release, and enhances BBB permeability while preserving antioxidant effects. These findings indicate that liposomal AP39 is a suitable therapeutic approach to further investigate in the treatment of neurodegenerative diseases.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"2067-2079"},"PeriodicalIF":4.7,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11930254/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143691412","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Recent Update of Natural Compounds as HIF-1α Inhibitors in Colorectal Carcinoma.","authors":"Pratibha Pandey, Sorabh Lakhanpal, Danish Mahmood, Lalji Baldaniya, Han Na Kang, Sungho Hwang, Sojin Kang, Min Choi, Seungjoon Moon, Shivam Pandey, Kamlesh Chaudhary, Fahad Khan, Bonglee Kim","doi":"10.2147/DDDT.S511406","DOIUrl":"10.2147/DDDT.S511406","url":null,"abstract":"<p><p>Hypoxia-inducible factor (HIF)-1 is a transcription factor that regulates the expression of target genes associated with oxygen homeostasis under hypoxic conditions, thereby contributing to tumor development and progression. Accumulating evidence has demonstrated that HIF-1α mediates different biological processes, including tumor angiogenesis, metastasis, metabolism, and immune evasion. Thus, overexpression of HIF-1α is strongly associated with poor prognosis in cancer patients. Natural compounds are important sources of anticancer drugs and studies have emphasized the decisive role of these mediators in modulating HIF-1α. Therefore, the pharmacological targeting of HIF-1α has emerged as a novel cancer therapeutic approach in recent years. The novelty of this review is that it summarizes natural products targeting HIF-1α in colorectal cancer that have not been presented earlier. We studied research publications related to the HIF-1α domain in cancer from 2010 to 2024. However, our main focus was to identify a better targeted approach for colorectal carcinoma management. Our review described HIF-1α role in tumor progression, summarizes the natural compounds employed as HIF-1α inhibitors, and discusses their potential in the development of natural compounds as HIF-1α inhibitors for colorectal cancer treatment.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"2017-2034"},"PeriodicalIF":4.7,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11929541/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143691508","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development and Characterization of LasR Immobilized Monolithic Column for Screening Active Ingredients as Quorum Sensing Inhibitors Against <i>P. aeruginosa</i> in Natural Products.","authors":"Zheng Liu, Yue Yang, Xiaoyuan Xie, Rui Li, Jifeng You, Xianglong Zhao, Yuanyuan Wang, Jialiang Guo","doi":"10.2147/DDDT.S501621","DOIUrl":"10.2147/DDDT.S501621","url":null,"abstract":"<p><strong>Background and aim: </strong>The enzyme/protein immobilized monolithic capillary combined with liquid chromatography-mass spectrometry is an efficient screening strategy for the corresponding agonist/antagonist. LasR is the potential therapeutic target since it plays a vital role in the colonization and invasion of <i>Pseudomonas aeruginosa</i> (<i>P. aeruginosa</i>). Therefore, reagents that inhibit LasR may be effective against <i>P. aeruginosa</i>. To screen and find LasR inhibitors rapidly, a LasR-immobilized monolithic capillary column was prepared and characterized.</p><p><strong>Methods: </strong>Firstly, the recombinant LasR protein was prepared in <i>E. coli</i>. Then, the LasR protein was immobilized to the surface of poly (glycidyl methacrylate-co-poly(ethylene glycol)diacrylate)-ethylenediamine monolithic column. The affinity and stability of prepared column was also evaluated. Furthermore, the prepared column was applied to fishing LasR inhibitor in <i>Scutellaria baicalensis Georgi</i> extract. The interaction of the screening compound to LasR was confirmed through molecular docking.</p><p><strong>Results: </strong>The recombinant active LasR protein was prepared in <i>E. coli</i>. After purification and validation, a comparative ligand fishing monolithic column was prepared through immobilizing LasR to the surface of the poly (glycidyl methacrylate-co-poly(ethylene glycol)diacrylate)-ethylenediamine through amidation reaction. The LasR was successfully immobilized to the monolithic column characterizing by Fourier transform infrared spectroscopy and scanning electron microscopy. The activity of immobilized LasR was reserved as it has affinity to the nature ligand 3-oxo-C₁₂-HSL and stablied within 24 h at 4 °C. In the <i>Scutellaria baicalensis Georgi</i> extract, baicalein was screened as a potential LasR inhibitor. The molecular docking results and the in vivo evaluation confirmed the activity of baicalein.</p><p><strong>Conclusion: </strong>The proposed LasR immobilized monolithic column is a viable strategy in screening LasR inhibitors. It can be considered as a possible alternative to traditional methods for screening LasR inhibitors as drug candidates against <i>P. aeruginosa</i>.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"2051-2064"},"PeriodicalIF":4.7,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11929421/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143691151","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Population Pharmacokinetic of Epidural Sufentanil in Labouring Women: A Multicentric, Prospective, Observational Study [Letter].","authors":"Shaojin Bu, Ling Wang, Jiaxi Tang","doi":"10.2147/DDDT.S524687","DOIUrl":"10.2147/DDDT.S524687","url":null,"abstract":"","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"2065-2066"},"PeriodicalIF":4.7,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11929511/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143691359","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}