Drug Development Research最新文献

{"title":"Oxindole–Coumarin Hybrids With Broad-Spectrum Anticancer Activity: Apoptosis Induction and Selective CA IX/XII Targeting","authors":"Hend I. Abdelaal,&nbsp;Abdalla R. Mohamed,&nbsp;Mohamed R. Elnagar,&nbsp;Simone Giovannuzzi,&nbsp;Samar H. Fahim,&nbsp;Hatem A. Abdel-Aziz,&nbsp;Claudiu T. Supuran,&nbsp;Sahar M. Abou-Seri","doi":"10.1002/ddr.70116","DOIUrl":"https://doi.org/10.1002/ddr.70116","url":null,"abstract":"<div>\u0000 \u0000 <p>A scaffold hybridization approach was utilized to enhance the antitumor and carbonic anhydrase inhibitory activity of our oxindole and coumarin lead compounds (<b>V</b> and <b>X</b>). Two oxindole-coumarin hybrids <b>6c</b> and <b>6e</b> showed broad spectrum of anticancer activity with NCI full panel MG-MIDs of 5.01 and 6.31 µM, respectively. They revealed GI₅₀ of a single digit micromolar concentration against 46 and 39 cell lines, respectively. An apoptosis dependent mechanism is suggested for the potent anticancer activity of compounds <b>6c</b> and <b>6e</b> via the increase in the BAX/BCL-2 ratio and enhancement of the expression levels of caspase-9 and the tumor suppressor p53. While this structure hybridization resulted in enhanced antitumor activity, it resulted in moderate CA IX and XII inhibitory activity. The potent anticancer compound <b>6e</b> was among the most active inhibitors of the tumor associated CA IX and CA XII in this study (K_I = 1.8 and 2.1 μM, respectively). As a result, even compound <b>6e</b>'s moderate CA IX/XII inhibitory activity may have synergistic effects contributing to its increased tumor growth suppression and proapoptotic activity. Moreover, compound <b>6e</b> revealed a nonsignificant cytotoxicity toward the normal kidney epithelial Vero cell line and was totally inactive against the cytosolic isoforms CA I and CA II (K_I = &gt; 100 μM) which mitigate its side effect as chemotherapeutic agent and enforce its safety profile.</p>\u0000 </div>","PeriodicalId":11291,"journal":{"name":"Drug Development Research","volume":"86 4","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144245066","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":"Decoding of the Role of TREM2 in Neuropathic Pain: Molecular Pathway and Neuroinflammatory Mechanism","authors":"Nithya Vijayan,&nbsp;Punniyakoti Veeraveedu Thanikachalam,&nbsp;Saraswati Patel","doi":"10.1002/ddr.70111","DOIUrl":"https://doi.org/10.1002/ddr.70111","url":null,"abstract":"<div>\u0000 \u0000 <p>Neuropathic pain is a debilitating condition characterized by chronic pain that is often refractory to conventional treatments. Increasing evidence suggests that microglia, the resident immune cells of the central nervous system, play a crucial role in modulating pain pathways through neuroinflammatory mechanisms. The Triggering Receptor Expressed on Myeloid Cells 2 (TREM2), in conjunction with DNAX-activating protein 12 (DAP12), regulates microglial activation and immune responses, thereby influencing neuropathic pain progression. This review explores the molecular mechanisms by which TREM2 contributes to pain modulation, focusing on its role in microglial activation, cytokine release, oxidative stress, and neuronal sensitization. Furthermore, we discuss the therapeutic potential of targeting TREM2 signaling for neuropathic pain management. Understanding the interplay between TREM2 and neuroinflammation offer novel insights into developing targeted interventions for chronic pain conditions.</p>\u0000 </div>","PeriodicalId":11291,"journal":{"name":"Drug Development Research","volume":"86 4","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144244753","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":"Irisin Protects Against Diabetic Cardiomyopathy by Suppressing Ferroptosis","authors":"Hongmei Ye,&nbsp;Jing Guo,&nbsp;Xinyu Wang,&nbsp;Bixian Chen,&nbsp;Lei Hu,&nbsp;Boyu Liu,&nbsp;Rongjing Song,&nbsp;Yufei Feng,&nbsp;Xiaohong Zhang","doi":"10.1002/ddr.70077","DOIUrl":"https://doi.org/10.1002/ddr.70077","url":null,"abstract":"<div>\u0000 \u0000 <p>Diabetic cardiomyopathy (DCM) is a major cause of mortality in patients with diabetes, particularly those with type 2 diabetes. Ferroptosis is closely linked to the onset and progression of various cardiovascular diseases. Irisin, a myokine produced by exercising skeletal muscle, has been shown to mitigate DCM. However, whether irisin alleviates type 2 DCM by inhibiting ferroptosis remains unclear. This study aimed to determine whether irisin prevents DCM by suppressing ferroptosis. First, ferroptosis was examined in palmitic acid (PA)-induced cardiomyocytes. Next, the effects of irisin on PA-induced cardiomyocytes were evaluated. Finally, the molecular mechanisms underlying irisin's protective effects against DCM were investigated. Ferroptosis was identified in an In Vitro model of type 2 DCM induced by PA. Irisin reduced PA-induced ferroptosis and alleviated myocardial injury, as indicated by decreased reactive oxygen species (ROS) production, Fe²⁺ content, and malondialdehyde (MDA) levels, along with increased glutathione (GSH) levels and mitochondrial membrane potential (MMP). Further analysis suggested that irisin does not mitigate PA-induced ferroptosis through iron metabolism or lipid peroxidation pathways but instead inhibits ferroptosis via the System Xc-/GSH/GPX4 axis. Additionally, irisin reduced the secretion of inflammatory cytokines, including IL-1β and IL-6. These findings indicate that irisin prevents the progression of DCM by suppressing ferroptosis through the System Xc-/GSH/GPX4 axis and reducing inflammation.</p></div>","PeriodicalId":11291,"journal":{"name":"Drug Development Research","volume":"86 4","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144197186","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":"Reactive Oxygen Species (ROS) and Their Profound Influence on Regulating Diverse Aspects of Cancer: A Concise Review","authors":"Rachana Tiwari,&nbsp;Ysani Mondal,&nbsp;Khyathi Bharadwaj,&nbsp;Mohita Mahajan,&nbsp;Sukanta Mondal,&nbsp;Angshuman Sarkar","doi":"10.1002/ddr.70107","DOIUrl":"https://doi.org/10.1002/ddr.70107","url":null,"abstract":"<div>\u0000 \u0000 <p>Reactive oxygen species (ROS) produced during cellular metabolism impacts normal cell functions, including signaling, hormone regulation, growth factors, ion transport, and apoptosis. Cells regulate ROS levels by using antioxidant enzymes and nonenzymatic detoxifying agents to avoid damage. It is important to focus on ROS and its involvement in cancer biology, particularly tumor progression and metastasis. Focus has been given to the involvement of ROS in various signaling cascades and its effect on various transcription factors that modulate cancer metastasis and tumorigenesis. For metastatic colonization to occur, endothelial cells must grow and migrate within pre-existing blood vessels, a process known as angiogenesis. The process benefits cancerous cells by providing them with oxygen and nutrients. Therefore, we have summarized the work carried out in this field too. We have further discussed how ROS triggers apoptosis, necroptosis, and ferroptosis, which are examples of regulated cell death (RCD) mechanisms that can demonstrate antitumor effects when they accumulate beyond a certain point. ROS are crucial to regulating and initiating apoptosis in cancerous cells, which affects the cell's ability to increase, survive, and respond to treatments. We have compiled work on integrated bioinformatics analysis to understand the involvement of ROS in cancer biology. We conclude through this review that ROS has a complex role in cancer biology, acting as promoters and tumorigenesis suppressors. Future research will likely focus on harnessing ROS's dual nature for therapeutic benefit while minimizing its harmful effects on normal cells.</p>\u0000 </div>","PeriodicalId":11291,"journal":{"name":"Drug Development Research","volume":"86 4","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144171987","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":"Functionalized Polydopamine Nanoparticles: A Promising Drug Delivery Platform for the Treatment of Tuberculosis","authors":"Nnamdi Ikemefuna Okafor,&nbsp;Precious Nnaji,&nbsp;Ngozi Francisca Nnolum-Orji,&nbsp;Yahya E. Choonara","doi":"10.1002/ddr.70109","DOIUrl":"https://doi.org/10.1002/ddr.70109","url":null,"abstract":"<p>Tuberculosis (TB) is considered a major infectious disease by the World Health Organization. The WHO estimates that there are 1.8 million TB deaths, and 10.4 million new cases of the disease reported yearly. While there are conventional therapies for TB, they have drawbacks such as a lengthy pill regimen, rigorous scheduling, and protracted treatment duration, which can result in strains of the disease that are multidrug-resistant (MDR) and extensively drug-resistant (XDR). Future TB control is at risk due to the emergence of MDR strains. This worry has made the hunt for a successful remedy necessary. One biomedical innovation has been the application of nanotechnology, which offers a fresh avenue of treating TB. Such nanotechnology approach includes Polydopamine (PDA) nanoparticles which have demonstrated the ability to reduce these difficulties. In recent times, PDA, which is an intriguing bioinspired polymer, has become a material of choice for designing drug delivery nano-systems. In fact, PDA nanoparticles show several intriguing characteristics, such as easy manufacturing approach, biocompatibility, the ability to scavenge free radicals, and photothermal and photoacoustic features. It is easily functionalized to promote blood circulation, cellular absorption, and drug release, among other functions. As a result, this review has examined the various PDA functionalization techniques aimed at overcoming MDR and enhancing TB treatment.</p>","PeriodicalId":11291,"journal":{"name":"Drug Development Research","volume":"86 4","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ddr.70109","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144140420","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":"Topical Miconazole Nanogel: In Vitro Characterization, In Vivo Skin Irritation, and Enhanced Antifungal Efficacy","authors":"Prajakta Chawalke,&nbsp;Ameeduzzafar Zafar,&nbsp;Abdulkarim S. Binshaya,&nbsp;Humood Al Shmrany,&nbsp;Ali Hazazi,&nbsp;Adil Abalkhail,&nbsp;Farhan R. Khan,&nbsp;Kranti Satpute,&nbsp;Shoaeb Mohammad Syed","doi":"10.1002/ddr.70106","DOIUrl":"https://doi.org/10.1002/ddr.70106","url":null,"abstract":"<div>\u0000 \u0000 <p>This study focused on the development of a miconazole nanogel formulation. The nanogel was prepared using the solvent diffusion method (high-speed homogenization) with Carbopol 940/chitosan/locust bean gum (Different gelling agents were used) and triethanolamine. The formulation was thoroughly evaluated for various physicochemical properties, including appearance, pH, FTIR analysis, viscosity, washability, spreadability, extrudability, drug content, entrapment efficiency, particle size, zeta potential, optical microscopy, differential scanning calorimetry (DSC), skin irritation, ex-vivo skin penetration, in-vitro diffusion, in-vitro antifungal activity, and stability. The prepared nanogel exhibited a clear, homogenous, white appearance with a pH compatible to skin pH (5.4−6.2). FTIR analysis confirmed the compatibility between the drug and polymers. The nanogel demonstrated good viscosity (3239−4175 cps), washability, and spreadability (2.5−3.5). Extrudability studies revealed easy extrusion of the formulation. Drug content ranged from 90.15% to 99.36%, with entrapment efficiency between 78.85% and 95.00%. The nanogel had a particle size of 534 nm and a zeta potential of −37.7 mV. Microscopic analysis showed spherical nanoparticles. DSC analysis indicated no change in the melting point of miconazole, which is one of the characteristics that confirm the stability of the drug with excipients. Skin irritation studies on rats revealed no erythema or edema after 24 h. In-vitro drug release ranged from 86.12% to 99.00%. Ex-vivo skin penetration and retention were higher for the nanogel than the marketed gel. In-vitro antifungal studies demonstrated superior activity of the nanogel compared to the marketed and standard formulations. Stability studies revealed no significant changes in drug content, extrudability, spreadability, pH, or in-vitro drug release. The developed miconazole nanogel formulation exhibited promising characteristics, including controlled drug release, enhanced skin penetration, and antifungal activity. It represents a potential advancement in topical antifungal therapy.</p>\u0000 </div>","PeriodicalId":11291,"journal":{"name":"Drug Development Research","volume":"86 4","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144140421","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":"Dose-Dependent Improvement of Caffeic Acid Against Acrylamide-Induced Male Reproductive Dysfunction","authors":"Divya Gupta,&nbsp;Sadhana Shrivastava,&nbsp;Sangeeta Shukla","doi":"10.1002/ddr.70103","DOIUrl":"https://doi.org/10.1002/ddr.70103","url":null,"abstract":"<div>\u0000 \u0000 <p>Dietary exposure to acrylamide is almost unavoidable and may result into long-term consequences. It has been reported to cause sexual dysfunction and even infertility. This study aimed to investigate the protective effects of caffeic acid against acrylamide-induced reproductive dysfunction in male rats. Group 1 served as the control; group 2 received acrylamide at a dose of 40 mg/kg for 10 days. In groups, 3–6, acrylamide was given as in group 2, followed by therapy of caffeic acid (10, 20, 30, 40 mg/kg) for 3 consecutive days. It was found that acrylamide causes significant alteration in serum concentrations of FSH, testosterone, and LH; decreased sperm motility and viability. Acrylamide administration causes alteration in biochemical parameters including lipid peroxidation, reduced glutathione, and antioxidant enzymes (SOD and CAT) along with triglyceride, cholesterol, and seminal fructose. Moreover, acrylamide causes histological alterations and promotes DNA damage as evident by COMET assay. After caffeic acid treatment, serological, biochemical, and histological alterations returned to almost normal ranges. Based on our findings, it is reasonable to conclude that caffeic acid, a natural antioxidant, is a potential medication to lessen any harmful damage in male gonads brought on by acrylamide consumption.</p>\u0000 </div>","PeriodicalId":11291,"journal":{"name":"Drug Development Research","volume":"86 4","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144108832","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":"Repurposing Nitroimidazoles: A New Frontier in Combatting Bacterial Virulence and Quorum Sensing via In Silico, In Vitro, and In Vivo Insights","authors":"El-Sayed Khafagy,&nbsp;Ahmed Al Saqr,&nbsp;Bjad K. Almutairy,&nbsp;Mohammed F. Aldawsari,&nbsp;Amr Selim Abu Lila,&nbsp;Tarek S. Ibrahim,&nbsp;Wael A. H. Hegazy,&nbsp;Ibrahim M. Salem","doi":"10.1002/ddr.70101","DOIUrl":"https://doi.org/10.1002/ddr.70101","url":null,"abstract":"<div>\u0000 \u0000 <p>The global antibiotic resistance crisis demands innovative strategies targeting bacterial virulence rather than survival. Quorum sensing (QS), a key regulator of virulence and biofilm formation, offers a promising avenue to mitigate resistance by disarming pathogens without bactericidal pressure. This study investigates the repurposing of nitroimidazoles as anti-QS and anti-virulence agents at subminimum inhibitory concentrations (sub-MICs). In Silico analyses, including molecular docking and molecular dynamics (MD) simulations, were performed to investigate ligand-receptor interactions with structurally distinct Lux-type QS receptors and assess binding stability and conformational dynamics over time. In Vitro assays evaluated the effects of representative nitroimidazoles, metronidazole (MET) and secnidazole (SEC), on QS-controlled phenotypes, including violacein production in <i>Chromobacterium violaceum</i> and biofilm formation and protease activity in <i>Pseudomonas aeruginosa</i>, <i>Acinetobacter baumannii</i>, <i>Salmonella enterica</i>, and <i>Proteus mirabilis</i>. In Vivo efficacy was assessed using a murine infection model and HeLa cell invasion assays. Molecular docking revealed high-affinity binding to QS receptors, corroborating their mechanistic interference. Sub-MIC MET/SEC significantly suppressed violacein synthesis, biofilm biomass, and protease secretion in Gram-negative pathogens. Both compounds reduced bacterial invasiveness in HeLa cells and In Vivo protected mice from lethal <i>P. aeruginosa</i> infections. Crucially, nitroimidazoles attenuated virulence without affecting bacterial viability, preserving microbial ecology. These findings position nitroimidazoles as dual-function agents; antimicrobial at bactericidal doses and anti-virulence at sub-MICs. Their validated efficacy across In Silico, In Vitro, and In Vivo models underscores their potential as adjunctive therapies, bridging the gap between drug repurposing and next-generation anti-infective development.</p>\u0000 </div>","PeriodicalId":11291,"journal":{"name":"Drug Development Research","volume":"86 3","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144085118","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":"Augmenting the Anti-Leukemic Activity of the BCL-2 Inhibitor Venetoclax Through Its Transformation Into Polypharmacologic Dual BCL-2/HDAC1 and Dual BCL-2/HDAC6 Inhibitors","authors":"Alexandria M. Chan,&nbsp;Christian Eberly,&nbsp;Brandon Drennen,&nbsp;Christopher C. Goodis,&nbsp;Zoe Wuyts,&nbsp;Curt I. Civin,&nbsp;Steven Fletcher","doi":"10.1002/ddr.70084","DOIUrl":"https://doi.org/10.1002/ddr.70084","url":null,"abstract":"<p>Motivated by the anti-leukemic synergy between histone deacetylase (HDAC) inhibitors and the FDA-approved BCL-2 inhibitor venetoclax, coupled with our interests in polypharmacology, we sought to bolster the anti-leukemic efficacy of the clinical drug by grafting HDAC1-selective or HDAC6-selective inhibitor motifs onto a solvent-accessible domain of venetoclax. We discovered multiple polypharmacological agents that both retained the potent BCL-2 inhibitory activity of venetoclax and effectively inhibited either HDAC1 or HDAC6 with excellent (up to 80-fold) selectivities for the desired HDAC isoform. In addition, relative to parental venetoclax, two of our lead compounds, <b>BD-4-213</b> and <b>AMC-4-154</b>, exhibited superior activities against the acute myeloid leukemia cell line MV4;11 and an MV4;11 cell line engineered to overexpress BCL-2. Annexin-V assay results confirmed an on-target mechanism of apoptosis for these novel chimeric molecules. Efforts to further boost the HDAC1 or HDAC6 binding affinities and/or selectivities proved unsuccessful due to synthetic chemistry challenges and solubility problems, which may underscore the difficulties of polypharmacology approaches involving a large inhibitor, such as venetoclax.</p>","PeriodicalId":11291,"journal":{"name":"Drug Development Research","volume":"86 3","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ddr.70084","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143949980","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":"Oleanolic Acid Alleviates Neuronal Ferroptosis in Subarachnoid Hemorrhage by Inhibiting KEAP1-Nrf2 and NF-κB Pathways","authors":"Lang Bojuan,&nbsp;Zhou Youdong,&nbsp;Wang Lei,&nbsp;Xue Lixin,&nbsp;Ma Jinyang","doi":"10.1002/ddr.70105","DOIUrl":"https://doi.org/10.1002/ddr.70105","url":null,"abstract":"<div>\u0000 \u0000 <p>Oleanolic acid (OA) is a pentacyclic triterpenoid compound, and we previously report that it ameliorates neurological injury in subarachnoid hemorrhage (SAH) model. However, the underlying mechanism is not clear. The aim of this study was to explore the effect and mechanism of OA on SAH. In this study, network pharmacology was applied to screen the targets of OA in SAH treatment. Based on these targets, protein-protein interaction network was constructed, and k-means cluster analysis was used to screen the core targets of OA in SAH treatment. In vitro SAH model was constructed with hemin-induced neuron HT22 and microglia BV2. Then cell counting Kit 8, flow cytometry, western blot, qPCR were performed to evaluate the effects of OA on neurons and microglia. 93 targets were identified as the core targets of OA in SAH treatment. Notably, these targets are closely related to neuroinflammation and oxidative stress responses. OA had good binding activity with KEAP1, NFKB1 and IKBA. OA significantly alleviated the inhibitory effect of hemin on HT22 cell viability. OA significantly inhibited the expression of CD86, promoted the expression of CD206, and promoted the transformation of microglia from M1 type to M2 type. Additionally, OA could inhibit the activation of NF-κB and KEAP1/Nrf2 pathways. In conclusion, OA ameliorates inflammatory response, oxidative stress and ferroptosis in SAH, and suppresses neuronal injury by inhibiting NF-κB and KEAP1/Nrf2 pathways.</p>\u0000 </div>","PeriodicalId":11291,"journal":{"name":"Drug Development Research","volume":"86 3","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143944493","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}