Drug Design, Development and Therapy最新文献

{"title":"Population Pharmacokinetics of Tranexamic Acid in Chinese Population Undergoing Cardiac Surgery with Cardiopulmonary Bypass.","authors":"Yue Liu, Chenghui Zhou, Hong Lv, Lei Tian, Juanjuan Jiang, Jia Shi","doi":"10.2147/DDDT.S493485","DOIUrl":"10.2147/DDDT.S493485","url":null,"abstract":"<p><strong>Background: </strong>Population pharmacokinetics (PK) models could provide specific references for the formulation of personal drug delivery protocols, however, there is no population PK study of tranexamic acid (TXA) have been conducted in the Chinese population. The aim of this study was to establish a population PK model based on the data of perioperative plasma concentrations in Chinese participants, and to provide a reference for individualized administration of TXA.</p><p><strong>Methods: </strong>Participants undergoing cardiac surgery were randomly assigned to high-dose of TXA group (a 30-mg/kg bolus, a 16-mg/kg/h maintenance dose, and a 2-mg/kg prime, n = 7) and low-dose group of TXA (a 10-mg/kg bolus, a 2-mg/kg/h maintenance dose, and a 1-mg/kg prime, n = 9). Blood samples were collected at 14 time points and the concentration of TXA was determined by liquid chromatography-tandem mass spectrometry. Modelling was performed using Phoenix NLME 8.3 software.</p><p><strong>Results: </strong>The primary covariate identified was body weight, while no significant influence of cardiopulmonary bypass (CPB) on the PK was detected. The population estimates for clearance (CL₁), volume of the central compartment (V₁), diffusional clearance (CL₂), and volume of peripheral compartment (V₂) were 4.7 L/h, 4.9 L, 17.0 L/h, and 11.1 L, respectively, assuming a bodyweight of 70 kg.</p><p><strong>Conclusion: </strong>This study provides the first population PK model of TXA in the Chinese population undergoing cardiac surgery with CPB. The model could serve as a reference for the future development of individualized TXA administration strategies, with target-controlled infusion (TCI) emerging as a viable option.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"4343-4353"},"PeriodicalIF":4.7,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12125134/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144198523","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":"Mechanism of Action and Efficacy of Wu-Hua-Yan-Xiao in the Treatment of Pediatric Acute Pharyngitis Based on Network Pharmacology and Experimental Validation.","authors":"Xinyun Zhang, Zengyu Zhang, Yingzi Xu, Jiawei Luo, Zihao Shen, Hao Liang, Yidi Zeng, Wanghua Liu, Caixing Zheng, Jinxia Li","doi":"10.2147/DDDT.S513073","DOIUrl":"10.2147/DDDT.S513073","url":null,"abstract":"<p><strong>Ethnopharmacological relevance: </strong>Wu-Hua-Yan-Xiao (WHYX) is an innovative volatile oil formulation derived from the traditional Yinqiao-Mabo decoction, developed for the treatment of pediatric acute pharyngitis.</p><p><strong>Materials and methods: </strong>Network pharmacology was utilized to identify active components and potential therapeutic targets of WHYX in acute pharyngitis. Compounds in WHYX were characterized using UHPLC-QE-MS. A pediatric acute pharyngitis rat model was established by administering 25% ammonia to the pharyngeal mucosa of young rats. WHYX was delivered via aerosol inhalation at gradient concentrations. Histopathological changes in pharyngeal tissues were evaluated by H&E staining. Serum levels of IL-6, IL-1β, TNF-α, and PGE2 were quantified by ELISA. Expression levels of TNF-α, TP53, IL17A, IL6, and Bcl-2 were assessed by qRT-PCR and Western blotting. Apoptosis was analyzed through immunofluorescence staining for Caspase-3 and TUNEL.</p><p><strong>Results: </strong>Network pharmacology identified 130 active compounds and 600 gene targets, with 194 overlapping drug-disease targets. TP53 signaling emerged as a central regulatory pathway. Compared with the model group, the high-dose WHYX volatile oil group showed marked improvements in pharyngeal pathology, significant reductions in inflammatory cytokines, downregulation of TNF-α, TP53, IL17A, IL6, and Bcl-2 expression, and suppressed apoptosis <i>(P</i> < 0.05). Therapeutic effects were comparable to or exceeded those observed in the positive control group. (<i>P < 0.05</i>).</p><p><strong>Conclusion: </strong>The WHYX formula alleviates inflammation, reduces apoptosis, and protects pharyngeal tissue in young rats with acute pharyngitis. Aerosol inhalation of WHYX presents a direct, effective, and non-invasive strategy for pediatric acute pharyngitis management.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"4321-4342"},"PeriodicalIF":4.7,"publicationDate":"2025-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12120256/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144180560","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":"Dasatinib Dose Optimization Based on Therapeutic Drug Monitoring in Patients with Chronic-Phase Chronic Myeloid Leukemia.","authors":"Fang Cheng, Zheng Cui, Qiang Li, Liu Wang, Yu Zhang, Weiming Li","doi":"10.2147/DDDT.S521260","DOIUrl":"10.2147/DDDT.S521260","url":null,"abstract":"<p><strong>Background: </strong>Although a dosage decrease regimen for chronic phase chronic myeloid leukemia (CML-CP) has been suggested, there is a marked lack of guidance on individualizing medication dosages for patients.</p><p><strong>Methods: </strong>Our aim was to explore the application of therapeutic drug monitoring (TDM) as a strategy for optimizing dasatinib dosage in patients with CML-CP.</p><p><strong>Results: </strong>It was observed that patients administered a dosage of 100 mg exhibited significantly higher concentrations than those given 50 mg, with no marked difference in concentration between branded and generic drugs. Further analysis unveiled a robust correlation between peak concentration (C_max) and clinical response (major molecular response (MMR): 103.8 ± 54.0 ng/mL versus 48.6 ± 13.9 ng/mL, P < 0.001; deep molecular response (DMR): 112.7 ± 57.6 ng/mL versus 66.2 ± 36.1 ng/mL, P = 0.001). Patients with a C_max >51.85ng/mL were more likely to achieve MMR, while those with a C_max surpassing 112.5 ng/mL had a higher probability of attaining DMR. We successfully implemented dasatinib dose reduction based on concentrations without loss of DMR in 22 patients undergoing first-line therapy. Moreover, trough concentrations (C_min) >2.48 ng/mL were closely associated with the onset of pleural effusion. Older patients demonstrated higher C_min and C_max, irrespective of whether they were on a 50 mg or 100 mg dosage regimen.</p><p><strong>Conclusion: </strong>TDM-based dose optimization could lead to beneficial clinical outcomes for patients with CML-CP. Furthermore, in terms of blood drug concentration, our findings supply additional evidence supporting the first-line treatment regimen of 50 mg daily.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"4311-4320"},"PeriodicalIF":4.7,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12109594/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144157451","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":"Semaglutide Alleviates Ovarian Oxidative Stress and Autophagy via the PI3K/AKT/mTOR Pathway in Mice with Polycystic Ovary Syndrome.","authors":"Sili Guo, Xiaohan Li, Mei Liu, Meiqi Feng, Xi Wang, Haibo Xue, Lei Zhang","doi":"10.2147/DDDT.S522730","DOIUrl":"10.2147/DDDT.S522730","url":null,"abstract":"<p><strong>Background: </strong>Polycystic ovary syndrome (PCOS) is a typical reproductive endocrine system disease with high incidence rate among childbearing age women. Several clinical data show that glucagon-like peptide-1 receptor agonists (GLP-1RAs) might have therapeutic effects on PCOS, but the mechanisms are still unclear. Here, we aim to assess the effects of semaglutide (a weekly preparation of GLP-1RAs) on PCOS in vivo.</p><p><strong>Methods: </strong>C57BL/6J female mice aged 3 weeks were subcutaneously injected with dehydroepiandrosterone and fed high-fat diet for 3 weeks to establish PCOS model. Then, we randomly divided the modeled mice into PCOS group (n=6), S-Low group (n=6), and S-High group (n=6). Additionally, six normal mice served as controls. Mice in S-Low and S-High group were intraperitoneally injected with corresponding dose of semaglutide every week for 4 weeks. The estrus cycle was observed daily. At the end of the experiment, body weight, blood glucose, and serum hormone levels were measured. Ovarian morphology was also observed. Then, the oxidative stress markers, autophagy-related proteins and CYP19A1, StAR, and CYP17A1 expression in ovarian tissue were measured. Finally, we used Western blot to detect the expression of PI3K/AKT/mTOR and downstream proteins.</p><p><strong>Results: </strong>After treatment with semaglutide, the estrous rhythm of PCOS mice was restored, the number of ovarian vesicles decreased, serum hormone imbalance corrected, and glucose tolerance improved. The relative expression of CYP17A1, StAR, Beclin-1, and LC3B, as well as MDA, were significantly reduced, while CYP19A1, p62, GSH, and SOD were significantly increased. Finally, semaglutide alleviates ovarian oxidative stress and autophagy via the PI3K/AKT/mTOR pathway.</p><p><strong>Conclusion: </strong>Semaglutide alleviates autophagy and ovarian oxidative stress via the PI3K/AKT/mTOR pathway in mice with PCOS.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"4297-4310"},"PeriodicalIF":4.7,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12109608/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144157460","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":"Olive Oil Solution of Volatile Oil from <i>Citri Reticulatae Pericarpium Viride</i> Alleviates Slow-Transit Constipation via Regulating SCF/c-Kit Signaling Pathway and Intestinal Flora.","authors":"Shuting Zou, Bin Xie, Zhentao An, Fang Li, Li Cui, Zhenhai Zhang, Weiquan Bu, Dandan He","doi":"10.2147/DDDT.S517114","DOIUrl":"10.2147/DDDT.S517114","url":null,"abstract":"<p><strong>Objective: </strong>The aroma of the aromatic class of traditional Chinese medicines can promote gastrointestinal peristalsis. This study aimed to explore the mechanisms by which volatile oil from <i>Citri Reticulatae Pericarpium Viride</i> (VOCRPV) alleviates slow-transit constipation (STC).</p><p><strong>Methods: </strong>The main active ingredients in VOCRPV were determined by High-Performance Liquid Chromatography (HPLC). Due to poor stability, an olive oil solution was prepared to enhance the volatile oil's stability. A mouse model of STC was induced using loperamide hydrochloride. The mice's body weight was monitored weekly. The number of fecal pellets, fecal water content, and small intestinal propulsion rate were detected. The colon tissues were analyzed using HE staining. The serum content of gastrointestinal hormones was measured using the corresponding ELISA kit. The protein expressions of stem cell factor (SCF) and c-Kit in colon tissues were detected by Western blot and immunohistochemistry methods. The 16S rRNA gene sequencing was used to detect the intestinal flora.</p><p><strong>Results: </strong>The contents of p-isopropyl toluene, γ-Terpinene, and d-Limonene were determined by HPLC. VOCRPV and its olive oil solution significantly enhanced body weight, increased the number of fecal pellets, improved fecal water content, and boosted small intestinal propulsion rate in mice with loperamide-induced STC, while also repairing colon mucosa damage. They also increased gastrin (Gas) and motilin (MTL) levels in treated mice, upregulated the expression of SCF and c-Kit proteins, and restored intestinal flora balance in STC mice.</p><p><strong>Conclusion: </strong>VOCRPV could effectively alleviate STC, and olive oil enhances its therapeutic effect. VOCRPV alleviates STC by elevating Gas and MTL levels, activating the SCF/c-Kit signaling pathway, and modulating intestinal flora.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"4275-4295"},"PeriodicalIF":4.7,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12107393/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144157455","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":"Dexmedetomidine Cannot Attenuate Liver Injury and Improve Outcomes Following Laparoscopic Living Donor Hepatectomy: A Randomised Controlled Trial.","authors":"Ling-Li Cui, Liang Zhang, Shen Liu, Qian Zhu, Fu-Shan Xue","doi":"10.2147/DDDT.S524343","DOIUrl":"10.2147/DDDT.S524343","url":null,"abstract":"<p><strong>Purpose: </strong>To determine the effects of intraoperative dexmedetomidine (DEX) administration on postoperative ischaemia/reperfusion injury (HIRI) and clinical outcomes of patients undergoing the laparoscopic living donor hepatectomy (LLDH).</p><p><strong>Patients and methods: </strong>Fifty-five patients who underwent the LLDH were randomly assigned to the DEX or control group. The DEX group received an intravenous infusion of DEX with an bolus dose of 1 µg/kg for 15 min before anaesthesia induction, followed by a continuous infusion at a rate of 0.4 µg/kg/h until the portal branch was disconnected. The control group was given an intravenous infusion of 0.9% saline at same volume and rate. The primary outcome was peak serum aspartate aminotransferase (AST) level during the first 72 h postoperatively. The secondary outcomes included other variables of postoperative liver and kidney function, intraoperative hemodynamic changes, postoperative recovery outcomes and the occurrence of complications.</p><p><strong>Results: </strong>The peak serum AST level during the first 72 h postoperatively was not significantly different between groups (DEX vs control: 288 [194-466] vs 324 [194-437] IU/L; difference, -1.2 IU/L; 95% CI, -86.9 to 88.0; <i>P</i>=0.973). The intraoperative mean artery pressure was not significantly different, but intraoperative heart rate was significantly decreased in the DEX group. There were no significant differences between groups in other secondary outcomes.</p><p><strong>Conclusion: </strong>This study demonstrates that intraoperative DEX administration at the studied dosage regimens cannot attenuate postoperative HIRI and does not improve clinical outcomes in patients undergoing the LLDH.</p><p><strong>Clinical trial registration: </strong>www.chictr.org.cn, ChiCTR2000040629.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"4263-4274"},"PeriodicalIF":4.7,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12105671/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144149720","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":"Bibliometrics Analysis and Knowledge Mapping of Fragment-Based Drug Design Research: Trends from 2015 to 2024.","authors":"Chenming He, Jirong Zhang, Runze Zhang, Liang Liu, Jielian Luo, Wen Zhang, Bangjiang Fang","doi":"10.2147/DDDT.S518489","DOIUrl":"10.2147/DDDT.S518489","url":null,"abstract":"<p><strong>Purpose: </strong>This study systematically analyzed available literature related to fragment-based drug design (FBDD) published between 2015 and 2024 using bibliometric methods to identify research trends, hotspots, and emerging frontiers. The findings provide valuable information and a comprehensive reference for future FBDD research and drug development.</p><p><strong>Methods: </strong>The relevant literature was comprehensively searched from the Web of Science Core Collection (WOSCC) database using the keywords \"Fragment-based drug design\" or \"FBDD\", covering articles published between January 1, 2015 and November 1, 2024. A total of 1,301 papers were included. Bibliometric analysis and knowledge mapping were conducted using the RStudio's bibliometrix-biblioshiny package, CiteSpace, and VOSviewer software, assessing multiple dimensions such as journal co-occurrence, keyword density, institutional collaboration, and citation patterns.</p><p><strong>Results: </strong>The research output in FBDD revealed fluctuating growth, with an average annual growth rate of 1.42%. The United States and China lead global research with 889 and 719 publications, respectively, contributing significantly to international collaboration (34.82%). Prominent research institutions included the Center National de la Recherche Scientifique (CNRS), the University of Cambridge, and the Chinese Academy of Sciences, demonstrating strong academic influence. Key contributors such as Abell, C. Blundell, TL, and Johnson, CN, were among the top ten high-impact authors, significantly shaping the FBDD landscape through highly cited publications. Influential journals included the <i>Journal of Medicinal Chemistry, Journal of Chemical Information and Modeling</i>, and the <i>European Journal of Medicinal Chemistry</i>, each highly recognized within the FBDD research community. Keyword analysis indicated core research directions focused on \"fragment-based drug discovery\", \"molecular docking\", and \"drug discovery\", reflecting key technological advancements and research hotspots.</p><p><strong>Conclusion: </strong>FBDD remains a dynamic field with ongoing global academic attention. Future research directions are likely to emphasize innovations in computational simulation, targeted drug screening, and molecular docking techniques, facilitating the advancement and development of novel therapeutic agents.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"4245-4262"},"PeriodicalIF":4.7,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12106911/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144157410","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":"Quality by Design Formulation Approach for the Development of Orodispersible Tablets of Dexlansoprazole.","authors":"Arbab Tahir Ali, Fazli Nasir, Talaya Hidayatullah, Sadia Pervez, Syeda Rabqa Zainab, Shazma Gohar, Altaf Ur Rahman, Muzna Ali Khattak, Fawaz Alasmari, Steven H Neau, Gul E Maryam","doi":"10.2147/DDDT.S515139","DOIUrl":"10.2147/DDDT.S515139","url":null,"abstract":"<p><strong>Purpose: </strong>Dexlansoprazole (DX) is a commercially available proton pump inhibitor (PPI). It is an oral delayed-release (DR) formulation that takes 1-2 h to reach the systemic circulation. To overcome the delayed onset of action of conventional formulation and patient inconvenience, orodispersible tablets (ODTs) have been formulated. Drug delivery systems, especially in elderly and frequent travelers, are limited by conventional dosage forms, and ODTs are an ideal dosage form for the fast onset of action and ease of administration for these patients and are more convenient than conventional tablets for patient compliance.</p><p><strong>Methods: </strong>The formulation was optimized via Design Expert^® software (version 13.0) and evaluated for in vitro and in vivo attributes. The ODTs were compressed by the most convenient method of compression, that is, direct compression, the formulation contains a combination of citric acid and sodium bicarbonate along with Kyron T-314^® (polymer). Pre- and post-compression evaluations were performed, and a comparative pharmacokinetic study of the DX ODT was carried out in human volunteers.</p><p><strong>Results: </strong>Drug plasma concentrations were analyzed at different time intervals through high-performance liquid chromatography (HPLC). PK Summit <b>^®</b> software was used to calculate various pharmacokinetic parameters. The pharmacokinetic results revealed that the T_max of 0.4 h was significantly lower than that of conventional DX, indicating rapid onset of action. Stability studies indicated that the formulation was stable under both intermediate and accelerated conditions.</p><p><strong>Conclusion: </strong>The ODTs exhibited good physical characteristics, with a pleasant taste and disintegrated rapidly in the saliva due to the addition of a superdisintegrant and an effervescent pair. Pharmacokinetics revealed a rapid therapeutic effect with good C_max. Furthermore, this formulation is cost-effective in terms of fewer manufacturing steps and a lower cost for excipients, along with a good stability profile.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"4163-4181"},"PeriodicalIF":4.7,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12103860/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144141570","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":"Zuogui Pill Promotes Neurovascular Regeneration and Corticospinal Tract Remodeling After Ischemic Stroke.","authors":"Dan Wu, Xiaohui Yan, Siqi Mei, Hao Hua, Xiaoyu Fei, Xinyu Xu, Yan Liu, Minghua Wu, Jian Zhu, Wenlei Li","doi":"10.2147/DDDT.S518696","DOIUrl":"10.2147/DDDT.S518696","url":null,"abstract":"<p><strong>Background: </strong>Ischemic stroke (IS) remains a leading cause of long-term disability. Neurovascular regeneration and remodeling of the corticospinal tracts are essential for neurological functional recovery. Zuogui pill (ZGP) has good efficacy in treating cerebral ischemia, but the mechanism remains unclear.</p><p><strong>Purpose: </strong>To investigate the effects of ZGP on angiogenesis, neurogenesis, corticospinal tract (CST) remodeling, and further evaluate its mechanisms of action in mice with ischemic stroke.</p><p><strong>Methods: </strong>Network pharmacology was used to analyze the active components, related targets, and mechanisms of ZGP's action in promoting neurovascular regeneration after ischemic stroke. Using a photothrombotic (PT) stroke mouse model, ZGP's effects on neurological recovery were assessed using behavioral tests. Angiogenesis and neurogenesis were evaluated by immunofluorescence of glucose transporter type 1(Glut-1) +/5-bromo-20-deoxyuridine (BrdU) + vessels and doublecortin (DCX)+/BrdU+ cells. CST remodeling was evaluated through diffusion tensor imaging (DTI). The levels of vascular endothelial growth factor (VEGF), brain-derived neurotrophic factor (BDNF), and mammalian target of rapamycin (mTOR) expression were tested by Western blot.</p><p><strong>Results: </strong>Network pharmacology identified 94 active ingredients and 83 overlapping targets related to IS and neurovascular regeneration. mTOR was identified as one of the core targets. Behavioral tests demonstrated ZGP significantly reduced error rates in irregular ladder walking (ZGP-H vs Stroke: p=0.003) and shortened sticker removal time (ZGP-H vs Stroke: p=0.003). Immunofluorescence revealed ZGP enhanced angiogenesis (Glut-1+/BrdU+ vessels: ZGP-H vs Stroke, p=0.018), neural progenitor cell proliferation and migration (BrdU+/DCX+ cells: ZGP-H vs Stroke: p=0.014). DTI showed increased fractional anisotropy (FA) in ipsilateral CST regions (ZGP-H vs Stroke: 0.001<p<0.05). Western blot confirmed elevated VEGF (p=0.002), BDNF (p=0.002), and p-mTOR/mTOR ratio (p<0.001) in peri-infarct tissues.</p><p><strong>Conclusion: </strong>ZGP promotes neurovascular regeneration, CST remodeling, and neurological function recovery after ischemic stroke. The positive impacts of ZGP are linked to heightened VEGF and BDNF expression and the activation of the mTOR pathway.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"4221-4243"},"PeriodicalIF":4.7,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12103873/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144141575","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":"PCOS and Inositols - Advances and Lessons We are Learning. A Narrative Review.","authors":"Guglielmo Lentini, Alessandro Querqui, Noemi Monti, Mariano Bizzarri","doi":"10.2147/DDDT.S524718","DOIUrl":"10.2147/DDDT.S524718","url":null,"abstract":"<p><strong>Introduction: </strong>This Expert Opinion covers recent updates in the use of Inositol in polycystic ovary syndrome (PCOS), highlighting the specific effects triggered upon ovarian steroidogenesis.</p><p><strong>Areas covered: </strong>An impressive body of evidence, obtained from molecular, animal and clinical studies, demonstrated the striking association between PCOS and the metabolism of myo-Inositol (myo-Ins) and its isomer D-Chiro-Inositol (DCI). Early investigations focused primarily on the metabolic consequences of inositol in modulating insulin transduction. However, recent advances disclosed that Inositols trigger direct effects on steroidogenesis. High DCI levels exacerbate androgen synthesis, and downregulate aromatase expression. Myo-Ins modulates insulin effects too, but exerts opposite actions on steroidogenesis, by increasing aromatase and FSH receptor expression. Clinical studies demonstrated myo-Ins efficacy, suggesting that an appropriate ratio in between myo-Ins/DCI (40:1) improves the reproductive function in PCOS women, even in absence of insulin resistance.</p><p><strong>Expert opinion: </strong>Inositol-based treatments in PCOS are gaining momentum, demonstrating safety and efficacy greater than those obtained with other pharmacological agents. The efficacy depends not only on the modulation of insulin sensitivity but also on the direct, steroidogenic effects upon the ovaries. Adequate adsorption of Inositol is a critical issue, and the association of α-Lactalbumin can significantly overcome this problem. However, if a treatment based on inositol could be equally effective on different phenotypes of PCOS needs a specific assessment.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"4183-4199"},"PeriodicalIF":4.7,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12104671/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144149728","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}