Drug Design, Development and Therapy最新文献

{"title":"Labor Epidural Anesthesia and Postpartum Depression Risk: Prospective Observation Study and Mendelian Randomization Analysis.","authors":"Wei Zheng, Ping Gan, Xianwen Wan, Xiuhong Wang, Jie Gong, Jia Min","doi":"10.2147/DDDT.S533306","DOIUrl":"10.2147/DDDT.S533306","url":null,"abstract":"<p><strong>Background: </strong>Postpartum depression is a common mental disorder in mothers. Although the association between pain and depression is generally accepted, it remains uncertain whether labor epidural analgesia can effectively reduce the risk of postpartum depression. The objective of this study was to investigate the association between labor epidural analgesia and postpartum depression.</p><p><strong>Methods: </strong>A total of 146 parturients with a single-term cephalic pregnancy who were preparing for vaginal delivery were recruited for this observational prospective study. The parturients were divided into a labor epidural analgesia group and a control group (routine care) by preference, with 73 in each group. Sociodemographic characteristics and peripartum data of the parturients were collected. Postpartum depression was defined as a score of ≥ 13 on the Edinburgh Postnatal Depression Scale (EPDS) at 6-weeks postpartum. Multivariable logistic analysis was applied to explore the risk factors for postpartum depression, and Mendelian randomization analyses were used to provide supporting evidence for the association between labor epidural analgesia and postpartum depression at the genetic level. Single-nucleotide polymorphisms associated with epidural or spinal anesthesia and postpartum depression were identified from publicly available genetic dataset of the United Kingdom biobank and FinnGen database.</p><p><strong>Results: </strong>There was no statistically significant difference in the incidence of postpartum depression at 6-weeks postpartum between the epidural and non-epidural groups [12 (16.4%) vs 7 (9.6%), <i>P</i> = 0.219]. The multivariable logistic model suggested that prepartum EPDS scores, satisfaction with income and marital status, pain level before anesthesia, and comorbidity during pregnancy were independent predictors of postpartum depression incidence. Mendelian randomization analyses indicated that neither labor epidural (OR = 0.90, 95% CI: 0.78-1.05; <i>P</i> = 0.18) nor spinal anesthesia (OR = 1.10, 95% CI: 0.96-1.27; <i>P</i> = 0.17) potentially reduced the risk of postpartum depression.</p><p><strong>Conclusion: </strong>These findings imply that administration of labor epidural analgesia during delivery has no influence on the incidence of postpartum depression.</p><p><strong>Registration number: </strong>The study protocol was registered in Chinese Clinical Trial Registry (ChiCTR2300078957).</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"8327-8338"},"PeriodicalIF":5.1,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12447957/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145111683","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":"Elucidating the Pharmacological Basis of Xianling Cifang Granules Against Breast Cancer. A Metabolomic Profiling Study.","authors":"Yang Wang, Rui Yang, Youyang Shi, Sheng Liu","doi":"10.2147/DDDT.S530516","DOIUrl":"10.2147/DDDT.S530516","url":null,"abstract":"<p><strong>Objective: </strong>To analyze the constituents and metabolic products of Xianling Cifang Granules (XLCF) in the serum of mice. The potential targets of XLCF in the treatment of breast cancer (BC) were explored by combining network pharmacology and molecular docking technology.</p><p><strong>Methods: </strong>Serum was collected from mice following oral administration of XLCF and analyzed using UHPLC-Q Exactive Orbitrap-MS. Absorbed prototype constituents and metabolites were identified by comparing retention times, accurate masses, MS/MS fragments, and isotopic patterns. Network pharmacology predicted potential therapeutic targets, and molecular docking (Autodock/Pymol) validated interactions between key constituents and targets.</p><p><strong>Results: </strong>Our comprehensive metabolomic profiling elucidates the pharmacological basis of XLCF against BC by identifying its absorbed constituents and their potential therapeutic links. It identified 122 prototype constituents of XLCF entering the systemic circulation. Icaritin (a metabolite derived from <i>Epimedium brevicornu Maxim</i>) was identified as a pivotal constituent due to its high bioavailability and established anti-BC activity, specifically inducing redox-mediated apoptosis via the SIRT6/NF-κB pathway and modulating the immunosuppressive microenvironment in triple-negative breast cancer (TNBC). Additionally, 62 serum metabolites exhibited significant alterations post-XLCF treatment, indicative of metabolic reprogramming involving carboxylation, hydroxylation, glucuronidation, and sulfation. Network pharmacology implicated inflammation and cellular metabolism pathways in the therapeutic effects of XLCF. Molecular docking confirmed that Icaritin, as the principal bioactive component, formed stable interactions with core targets ADORA1, AKR1B1, and ADORA3.</p><p><strong>Conclusion: </strong>This integrated approach delineates the anti-BC mechanism of XLCF, 122 absorbed constituents (with Icaritin as key) and 62 altered metabolites drive systemic metabolic reprogramming, acting through ADORA1, AKR1B1 and ADORA3 targets to modulate critical pathways. These findings provide robust pharmacological evidence supporting the clinical application of XLCF against BC and demonstrate the value of combining metabolomics with target prediction for Traditional Chinese Medicine (TCM) research. Experimental validation of the identified targets is warranted.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"8213-8236"},"PeriodicalIF":5.1,"publicationDate":"2025-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12442908/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145085281","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":"LC-MS-Based Serum Metabolomic Analysis Predicts the Risk of Tigecycline-Induced Coagulopathy in Critically Ill Patients.","authors":"Na Yang, Xinxin Zheng, Xinyue Ji, Hui Yao, Ke Xu, Tianqi Zhang, Lu Jin, Huaijun Zhu, Min Wang","doi":"10.2147/DDDT.S539874","DOIUrl":"10.2147/DDDT.S539874","url":null,"abstract":"<p><strong>Purpose: </strong>Tigecycline is widely used to treat multidrug-resistant infections. However, the high incidence of coagulopathy poses a significant clinical challenge. This observational study aimed to characterize the metabolomic profiles of critically ill patients receiving tigecycline and to identify potential metabolic traits to predict tigecycline-induced coagulopathy (TIC).</p><p><strong>Patients and methods: </strong>A total of 53 patients were enrolled and classified into TIC and non-TIC groups. Serum samples were collected at trough (Cmin), mid-dose (C1/2), and peak (Cmax) tigecycline concentrations. LC-MS-based untargeted metabolomics was applied to characterize metabolic profiles across these timepoints and to identify metabolites potentially predictive of TIC.</p><p><strong>Results: </strong>By sequentially applying univariate analysis and multivariate LASSO-penalized Cox proportional hazards regression analysis, we identified 10, 10, and 9 metabolites at the Cmin, C1/2, and Cmax timepoints, respectively, as predictive markers of TIC. Importantly, patients with lower levels of lysophosphatidylcholines (LysoPCs) and lysophosphatidylethanolamines (LysoPEs) are more susceptible to coagulopathy following tigecycline therapy. In particular, receiver operating characteristic curve analysis of LysoPC (18:0), LysoPC (18:3), LysoPE (18:0), and LysoPE (18:4) measured at Cmin demonstrated an area under the curve close to 0.8, providing strong evidence for their potential as robust biomarkers for predicting TIC.</p><p><strong>Conclusion: </strong>Our study indicated that metabolomics could be a valuable tool for predicting the risk of TIC and suggested that LysoPCs and LysoPEs might serve as hypothesis-generating candidates for future studies exploring potential therapeutic interventions.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"8237-8250"},"PeriodicalIF":5.1,"publicationDate":"2025-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12442925/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145085336","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":"Clinical Benefits and Challenges of Esketamine in Elderly Patients During the Perioperative Period.","authors":"Shuai Zhang, Chen Bai, Mingcan Xu, Yiqing Li, Ying Han, Yanwu Jin, Xin Zhao","doi":"10.2147/DDDT.S536813","DOIUrl":"10.2147/DDDT.S536813","url":null,"abstract":"<p><p>Ketamine is a classic intravenous anesthetic. Esketamine is a dextro-isomer of ketamine, with similar mechanism of action, mainly through non-competitive antagonism of N-methyl-D-aspartate receptors, higher potency and fewer adverse effects. The characteristics of esketamine include circulatory stimulation, bronchodilatation, inhibition of inflammation and dissociative anesthetic properties. Esketamine was approved for clinical practice in China in 2019, and has significant advantages for use in pediatric, maternal, elderly or shock patients. The clinical use of esketamine is currently receiving widespread attention. This article reviews the recent progress and limitations of clinical studies on the perioperative use of esketamine in elderly patients, covering its pharmacological properties, hemodynamic effects, analgesic benefits, and impacts on depression, sleep, and neurocognitive function, to provide theoretical reference for its application in anesthesia and offer dosage recommendations for elderly patients.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"8251-8263"},"PeriodicalIF":5.1,"publicationDate":"2025-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12442823/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145085350","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":"<i>Panax notoginseng</i> Saponins Improve Angiogenesis in Coronary Heart Disease Based on the microRNA 200a Methylation Pathway [Retraction].","authors":"","doi":"10.2147/DDDT.S566623","DOIUrl":"https://doi.org/10.2147/DDDT.S566623","url":null,"abstract":"<p><p>[This retracts the article DOI: 10.2147/DDDT.S488036.].</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"8211-8212"},"PeriodicalIF":5.1,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12439814/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145079767","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":"Effect of Fospropofol Disodium on Perioperative Neurocognitive Function in Elderly Patients Undergoing Total Hip Arthroplasty.","authors":"Hongrui Zhu, Zaibao Wang, Sheng Ding, Chunliu Li, Li Xie, Yan Meng, Jiawei Xiao, Wuyang Zhang, Min Xu, Chen Gao, Keqiang He, Sheng Wang","doi":"10.2147/DDDT.S548597","DOIUrl":"10.2147/DDDT.S548597","url":null,"abstract":"<p><strong>Objective: </strong>This study aimed to compare the effects of fospropofol disodium and propofol on perioperative neurocognitive function in elderly patients undergoing total hip arthroplasty (THA), evaluating the non-inferiority of fospropofol disodium in preventing or reducing perioperative neurocognitive disorders (PND) and exploring optimal clinical anesthesia strategies.</p><p><strong>Methods: </strong>A total of 180 elderly patients (aged 65~80 years) scheduled for THA between November 2022 and November 2024 were randomly assigned to the fospropofol disodium group (Group F, n=90) or the propofol group (Group P, n=90). Cognitive function was assessed preoperatively (1 day before surgery) and postoperatively (1, 3, 7 days, and 1 month) using the Modified Mini-Mental State Examination (MMSE), 3-Minute Diagnostic Interview for Confusion Assessment Method (3D-CAM), Digit Span Test (DST), Verbal Fluency Test (VFT), and Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE). The incidence of postoperative cognitive dysfunction (POCD) and delirium (POD), hemodynamic parameters, and adverse events were compared between the two groups.</p><p><strong>Results: </strong>No significant differences were observed between the two groups in the incidence of POCD (<i>p</i>>0.05) or POD (<i>p</i>>0.05) at any postoperative time point. At the time point of 10 minutes after bone cement implantation (T4), the heart rate of patients in the Group F was higher than that of Group P (<i>p</i> < 0.0001). At the time of discharge from the PACU, the heart rate of patients in the Group F was lower than that of the Group P (<i>p</i> = 0.037). Group F exhibited higher mean arterial pressure (MAP) at the beginning of the operation (<i>p</i>=0.022) and a longer extubation time and waking time (<i>p</i> < 0.001) but had significantly lower incidences of injection pain (<i>p</i>=0.018) and postoperative nausea and vomiting (<i>p</i>=0.037). Binary logistic regression identified age as an independent risk factor for PND [OR=1.149, <i>p</i>=0.006], while preoperative MMSE score was a protective factor [OR=0.693, <i>p</i> = 0.002].</p><p><strong>Conclusion: </strong>Fospropofol disodium may be a viable alternative in settings where injection pain and PONV are primary concerns, provided that hemodynamic stability is actively managed in elderly THA patients, with non-inferior efficacy in preventing PND compared to propofol and fewer adverse effects. Age and preoperative cognitive function are critical predictors of PND, warranting careful consideration in perioperative management.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"8195-8209"},"PeriodicalIF":5.1,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12439819/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145079790","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":"Traditional Chinese Medicine in the Comprehensive Management of Tourette Syndrome: Insights from Genetics and Pathophysiology: A Review.","authors":"Xinkang Yu, Mingya Zhu, Qiwei Tang, Shaojie An, Hao Tan, Xianpei Wang, Jiali Zhang, Jinna Tian, Jianbao Li","doi":"10.2147/DDDT.S542423","DOIUrl":"10.2147/DDDT.S542423","url":null,"abstract":"<p><p>Tourette syndrome (TS) is a neurodevelopmental disorder characterized by recurrent motor and vocal tics, often accompanied by comorbid psychiatric symptoms. While pharmacological treatments are commonly used, they often provide incomplete symptom relief and may cause adverse effects. Traditional Chinese Medicine (TCM) has been increasingly applied in clinical practice and is considered a valuable complementary approach. This review summarizes current research on TS from the perspectives of genetics, pathophysiology, and TCM, with particular attention to how biological findings inform syndrome differentiation and treatment. Genetic studies have identified polymorphisms such as IL1RN and SLC1A3, which are associated with immune dysfunction and neurotransmitter imbalance, respectively. These findings may correspond to TCM syndromes such as \"Liver Wind Stirring Internally\", linked to inflammation, and \"Liver Yin Deficiency with Yang Hyperactivity\", associated with excitatory overactivity. Pathophysiological mechanisms, including cortico-striato-thalamo-cortical (CSTC) circuit abnormalities and dopaminergic dysregulation, have been recognized as core contributors to tic development. TCM interventions appear to target these mechanisms. Tianma Gouteng Decoction has been shown to regulate neurotransmitter function and reduce liver yang hyperactivity, while Ningdong Granule can inhibit neuroinflammatory responses by modulating microglial activity. These effects are consistent with modern findings on the neural and immune changes observed in TS. Moreover, clinical evidence supports that combining TCM with Western pharmacotherapy may improve overall treatment efficacy, reduce side effects, and enhance patient outcomes. By linking genetic and neural mechanisms with traditional syndrome patterns, this review offers a comprehensive framework for understanding and applying TCM in TS treatment. The integration of TCM principles with modern scientific knowledge may support more individualized and biologically informed approaches to care.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"8181-8194"},"PeriodicalIF":5.1,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12435501/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145074615","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":"From C481 Resistance Evasion to Platelet Preservation: Rilzabrutinib Redefines ITP Targeted Therapy.","authors":"Long Liu, Yang Xiao, Yanyan Jia, Ziyi Shao, Jingfei Shi, Chao Cui","doi":"10.2147/DDDT.S543620","DOIUrl":"10.2147/DDDT.S543620","url":null,"abstract":"<p><p>Immune thrombocytopenia (ITP), as an autoimmune disease, has various limitations in traditional treatments, and there is a lack of safe and durable targeted therapeutic regimens for refractory patients. Traditional covalent Bruton's tyrosine kinase (BTK) inhibitors are difficult to apply in ITP treatment due to issues such as drug resistance and bleeding risks. As a reversible covalent BTK inhibitor, rilzabrutinib has dual advantages in its molecular design: in terms of evading C481 resistance, it targets the ATP-binding domain of BTK through a non-covalent bond-dominated mode, and maintains highly efficient inhibitory activity in the BTK C481S mutant cell model (with an in vitro IC50 of 1.2 nM), showing significant advantages over traditional covalent inhibitors (eg, ibrutinib, whose IC50 increases to 1 μM); in terms of platelet function protection, in vivo mouse experiments have confirmed that it can reduce venous thrombosis, block the BTK pathway to decrease autoantibody-mediated platelet destruction, and retain the functions of pathways such as G protein-coupled receptors, achieving a balance between abnormal immune suppression and platelet hemostatic function through \"on-demand inhibition\". Preclinical studies have shown that its binding to human blood BTK is time- and concentration-dependent, and the inhibition of the BTK pathway in B cells and basophils is closely related to the degree of binding, with moderate kinase selectivity. Clinical studies have confirmed that the drug can take effect quickly, with 43% of patients achieving a platelet count ≥50×10⁹/L after 12 weeks of treatment, and the incidence of bleeding events is low. This article systematically analyzes the value of rilzabrutinib from molecular design to clinical translation, and elaborates on its mechanism of overcoming drug resistance and its synergistic regulatory effect on the B cell-macrophage-platelet pathological network. At present, its rapid onset, high safety, and effectiveness in refractory cases have been preliminarily verified, but long-term data from Phase III clinical trials are still needed to support its use as a first-line treatment. It provides a new therapeutic hope for patients with refractory ITP and also offers a paradigmatic reference for the development of kinase inhibitors for autoimmune diseases.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"8161-8180"},"PeriodicalIF":5.1,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12435525/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145074532","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":"Pharmacokinetics and Bioequivalence of Mycophenolate Sodium Enteric-Coated Tablets Under Fasting and Fed Conditions: A Single-Dose, Open-Label, Four-Period Replicated Crossover Study in Healthy Chinese Male Subjects.","authors":"Peiwen Zhang, Mupeng Li, Hao Jiang, Fangfang Liu, Qian Huang, Yangyun Han, Lianlian Fan","doi":"10.2147/DDDT.S529915","DOIUrl":"10.2147/DDDT.S529915","url":null,"abstract":"<p><strong>Aim: </strong>Enteric-coated mycophenolate sodium (EC-MPS) is an immunosuppressant used to prevent organ rejection in kidney transplant patients. This study assesses the pharmacokinetics and bioequivalence of a generic EC-MPS formulation (180 mg) relative to the branded product (Myfortic^®), and investigates the effect of food on its pharmacokinetic behavior.</p><p><strong>Methods: </strong>A single-dose, open-label, four-period replicated crossover study with a 7-day washout was conducted in 60 healthy Chinese male subjects under fasting and fed conditions. Eligible subjects were enrolled in two independent trials (fasting and fed conditions) and randomized 1:1 into two treatment sequence groups, with 15 subjects per group. In each group, subjects received a single 180 mg oral dose of the generic or branded product after a 10-hours overnight fast. Plasma concentrations of mycophenolic acid were quantified using a validated LC-MS/MS method. Primary pharmacokinetic parameters (C_max, AUC_0-48, and AUC_0-inf) were evaluated via a non-compartmental model and analyzed by analysis of variance. Bioequivalence was determined using reference-scaled average bioequivalence (RSABE) for highly variable parameters (CV ≥30%) and average bioequivalence (ABE) otherwise, with 90% confidence intervals (CIs) within 80.00%-125.00%.</p><p><strong>Results: </strong>All subjects completed the study. Bioequivalence was established between the generic and branded formulations under both fasting and fed conditions. In the fasting cohort, 90% CIs for the geometric mean ratios (GMRs) of C_max, AUC_0-48, and AUC_0-inf all fell within 80.00%-125.00%, meeting ABE criteria. In the fed cohort, GMRs for C_max and AUC_0-inf were 119.74% and 99.87%, respectively, within RSABE acceptance limits. Food intake delayed drug absorption, resulting in a notable lag time (median T_max 7.0 h vs 2.5-3.0 h, p<0.01) and increased inter- and intra-individual variability. Twenty mild adverse events (AEs) were reported; no serious AEs occurred.</p><p><strong>Conclusion: </strong>The generic EC-MPS demonstrated bioequivalence to the branded product under all tested conditions, supporting its clinical interchangeability. Both formulations were well tolerated in healthy Chinese males.</p><p><strong>Clinical trial registration: </strong>http://www.chictr.org.cn/, Registration No: ChiCTR2300075403.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"8069-8081"},"PeriodicalIF":5.1,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12434611/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145074540","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":"Natural Products from Chinese Medicine Targeting NF-κB Signaling: Emerging Therapeutic Avenues for Neurodegenerative Diseases.","authors":"Lihui Wang, Lina Feng, Baicheng Ning, Zhuolin Wang, Chunmei Dai, Mingquan Li","doi":"10.2147/DDDT.S534706","DOIUrl":"10.2147/DDDT.S534706","url":null,"abstract":"<p><p>This review summarizes recent advances in leveraging natural products from Chinese medicine to modulate the nuclear factor kappa B (NF-κB) signaling pathway for the prevention and treatment of neurodegenerative diseases (NDDs), focusing specifically on Alzheimer's disease (AD), Parkinson's disease (PD), and Amyotrophic lateral sclerosis (ALS). NF-κB proteins regulate cellular biological activity by binding to promoter regions in the nucleus and transcribing various protein-coding genes. Emerging evidence indicates that NF-κB plays a pivotal role in driving key hallmarks of NDD progression, including neuroinflammation, oxidative stress, mitochondrial dysfunction, and dysregulation of the cell cycle. Natural products from Chinese medicine exert modulatory effects on NF-κB signaling through diverse pharmacological mechanisms, ultimately improving cognitive and motor impairments in preclinical NDDs models. The pleiotropic nature of natural products derived from traditional Chinese medicine (TCM)-which operate through subunit-specific modulation of NF-κB-underscores their potential as next-generation therapeutics. Investigating the intricate regulation of NF-κB by natural products from Chinese medicine will not only enrich our understanding of the pathogenesis of NDDs but also establish a theoretical foundation for the development of new therapeutic drugs for NDDs, providing innovative strategies for prevention and treatment.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"8135-8159"},"PeriodicalIF":5.1,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12433662/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145069325","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}