Xenobiotica最新文献

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In vitro evaluation of norwogonin as a potential inhibitor of cytochrome P450 forms 3A4, 2D6, and 2C9. Norwogonin作为细胞色素P450形式3A4、2D6和2C9潜在抑制剂的体外评价
IF 1.5 4区 医学
Xenobiotica Pub Date : 2026-03-01 Epub Date: 2026-02-26 DOI: 10.1080/00498254.2026.2626346
Xianjie He, Dong Zhang, Hui Chen
{"title":"In vitro evaluation of norwogonin as a potential inhibitor of cytochrome P450 forms 3A4, 2D6, and 2C9.","authors":"Xianjie He, Dong Zhang, Hui Chen","doi":"10.1080/00498254.2026.2626346","DOIUrl":"10.1080/00498254.2026.2626346","url":null,"abstract":"<p><p>Norwogonin, a bioactive flavonoid with anti-inflammatory and anticancer potential. Its interactions with cytochrome P450 enzymes remain uncharacterised. This study aimed to investigate the effect of norwogonin on the activity of P450s.The inhibitory effects of norwogonin on P450 forms (1A2, 2A6, 2C8, 2C9, 2C19, 2D6, 2E1, 3A4) were evaluated using pooled human liver microsomes (HLMs). Dose-dependent inhibition assays (0-100 μM norwogonin) and time-dependent studies (0-30 min incubation) were conducted with form-specific probe substrates. Metabolites were quantified <i>via</i> High Performance Liquid Chromatography (HPLC).Norwogonin selectively inhibited 2C9, 2D6, and 3A4 (IC<sub>50</sub>: 13.05 ± 4.62, 11.33 ± 2.21, and 7.52 ± 0.61 μM, respectively), with 3A4 exhibiting the highest sensitivity. Kinetic analysis revealed distinct inhibitory mechanisms of norwogonin: non-competitive for 3A4 (<i>K<sub>i</sub></i> = 3.755 μM) and competitive for 2C9 (<i>K<sub>i</sub></i> = 6.879 μM) and 2D6 (<i>K<sub>i</sub></i> = 6.028 μM). Time-dependent inhibition (TDI) of norwogonin was observed exclusively for 3A4, characterised by increasing suppression with prolonged incubation (<i>K<sub>I</sub></i> = 2.323 μM<sup>-1</sup>, <i>K<sub>inact</sub></i> = 0.035 min<sup>-1</sup>), while 2C9/2D6 inhibition remained static over time.Norwogonin selectively inhibited 2C9, 2D6, and 3A4 <i>via</i> distinct mechanisms, with time-dependent 3A4 suppression suggesting the potential interactions, necessitating caution in co-administered therapies.</p>","PeriodicalId":23812,"journal":{"name":"Xenobiotica","volume":" ","pages":"214-221"},"PeriodicalIF":1.5,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146150628","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}
引用次数: 0
Effect of plantamajoside on the pharmacokinetics of nifedipine in rats and the underlying mechanisms. 车前草皂苷对硝苯地平大鼠药动学的影响及其机制。
IF 1.5 4区 医学
Xenobiotica Pub Date : 2026-02-01 Epub Date: 2026-02-16 DOI: 10.1080/00498254.2026.2621364
Shaorong Huang, Fangwu Su, Meng Lei
{"title":"Effect of plantamajoside on the pharmacokinetics of nifedipine in rats and the underlying mechanisms.","authors":"Shaorong Huang, Fangwu Su, Meng Lei","doi":"10.1080/00498254.2026.2621364","DOIUrl":"10.1080/00498254.2026.2621364","url":null,"abstract":"<p><p>Plantamajoside was reported to possess blood pressure-lowering effects. This study explores how plantamajoside affects the pharmacokinetics of nifedipine, providing valuable insights for clinical drug use.This study examined the effect of plantamajoside on nifedipine pharmacokinetics. Sprague-Dawley rats (<i>n</i> = 6 per group) were administered nifedipine orally, either alone or after pre-treatment with plantamajoside. Blood concentrations of nifedipine were measured using liquid chromatography-tandem mass spectrometry. The effects of plantamajoside on nifedipine metabolic stability and cytochrome P450 3A (CYP3A) activity were evaluated in rat liver microsomes (RLMs).Co-administration of nifedipine with plantamajoside altered its pharmacokinetics, including elevated peak plasma concentration (C<sub>max</sub>), increased area under the concentration-time curve (AUC)<sub>(0-t)</sub>, prolonged elimination half-life (t<sub>1/2</sub>), and reduced apparent clearance (CL/F). <i>In vitro</i>, plantamajoside enhanced the metabolic stability of nifedipine, extending its t<sub>1/2</sub> and lowering intrinsic clearance. Plantamajoside also inhibited CYP3A activity in RLMs (half maximal inhibitory concentration, IC<sub>50</sub> = 13.96 μM; inhibition constant, K<sub>i</sub> = 7.10 μM).The increased nifedipine exposure in rats could be attributed to the inhibition of CYP3A-mediated metabolism by plantamajoside. Given the role of orthologous CYP3A4 in humans, this interaction may enhance antihypertensive efficacy but could also increase the risk of severe hypotension clinically.</p>","PeriodicalId":23812,"journal":{"name":"Xenobiotica","volume":" ","pages":"171-177"},"PeriodicalIF":1.5,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146150688","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}
引用次数: 0
Pharmacokinetic interaction between pachymic acid and tacrolimus and its potential mechanisms in rats. 厚青酸与他克莫司在大鼠体内的药动学相互作用及其可能机制。
IF 1.2 4区 医学
Xenobiotica Pub Date : 2026-02-01 Epub Date: 2026-01-06 DOI: 10.1080/00498254.2025.2612030
Yingzi Zhang, Ruiqing Yan, Dong Zhang, Hongchuan Guo
{"title":"Pharmacokinetic interaction between pachymic acid and tacrolimus and its potential mechanisms in rats.","authors":"Yingzi Zhang, Ruiqing Yan, Dong Zhang, Hongchuan Guo","doi":"10.1080/00498254.2025.2612030","DOIUrl":"10.1080/00498254.2025.2612030","url":null,"abstract":"<p><p>Tacrolimus is a novel immunosuppressor for its significant anti-inflammation and immune activity, which would induce hyperglycaemia, increasing its combination with hypoglycaemic drugs.Pachymic acid has been demonstrated to possess the pharmacological activity of anti-hyperglycaemia. Tacrolimus combining pachymic acid was investigated, aiming to guide the prescription of patients taking tacrolimus.In rats, 1.2 mg/kg tacrolimus was combined with three dosages of pachymic acid (50, 100, and 200 mg/kg) with the single dosage of tacrolimus as control. The blood glucose of rats with different medications was monitored and the pharmacokinetic changes of tacrolimus were assessed. Tacrolimus significantly increased the blood glucose of rats. Pachymic acid increased C<sub>max</sub>, AUC, and t<sub>1/2</sub> and reduced the clearance rate of tacrolimus in rats, and the effects were promoted by its increasing dosage. The metabolic stability of tacrolimus in rat liver microsomes was also improved by pachymic acid, both of which enhanced its hyperglycaemic effect in rats. Significant inhibition of CYP3A1/2 by pachymic acid was observed with the IC<sub>50</sub> value of 12.25μM.Co-administration of tacrolimus with pachymic acid induced adverse interactions, suppressing the metabolism and enhancing the hyperglycaemic effect of tacrolimus through inhibiting CYP3A1/2.</p>","PeriodicalId":23812,"journal":{"name":"Xenobiotica","volume":" ","pages":"164-170"},"PeriodicalIF":1.2,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145901190","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}
引用次数: 0
4D-DIA proteomics analysis revealed the network pharmacological mechanism of Astragaloside IV for the treatment of diabetic retinopathy. 4D-DIA蛋白质组学分析揭示了黄芪甲苷治疗糖尿病视网膜病变的网络药理机制。
IF 1.2 4区 医学
Xenobiotica Pub Date : 2026-02-01 Epub Date: 2026-01-25 DOI: 10.1080/00498254.2025.2612600
Xingyi Zhang, Hua Liu
{"title":"4D-DIA proteomics analysis revealed the network pharmacological mechanism of Astragaloside IV for the treatment of diabetic retinopathy.","authors":"Xingyi Zhang, Hua Liu","doi":"10.1080/00498254.2025.2612600","DOIUrl":"10.1080/00498254.2025.2612600","url":null,"abstract":"<p><p>To investigate the protective mechanism of Astragaloside IV (AS-IV) in diabetic retinopathy(DR).A streptozotocin-induced diabetic rat model was established and divided in to three groups: control, DR, and DR + AS-IV. Retinal injury was assessed using optical coherence tomography (OCT). Retinal proteomes were profiled using 4D-DIA proteomics. Candidate genes were validated using quantitative PCR (qPCR).302 differentially expressed proteins were detected. Venn diagram analysis revealed three down-regulated proteins in the DR group: Gnal, Dennd1a, and Snx13, and two up-regulated proteins: Ogn and Mylpf. AS-IV treatment reversed the expression of Dennd1a and Gnal while downregulating Ogn, Mylpf, and Snx13. PPI analysis revealed limited direct connectivity among the five proteins but identified 10 additional interactors, including MYLK, ADCY9, and RAB35. GO analysis indicated involvement in muscle contraction, muscle myosin complex, and phosphatidylinositol phosphate binding and structural molecule activity. KEGG analysis highlighted calcium signalling as a key pathway. Molecular docking demonstrated stable interactions between AS-IV and Dennd1a, Ogn, and Snx13 proteins. qPCR confirmed significant regulation of Dennd1a and Ogn, while Snx13 and Mylpf changes were not significant.AS-IV exhibited protective effects against diabetic retinal injury by modulating Dennd1a and Ogn, implicating calcium signalling and structural pathways in its therapeutic mechanism.</p>","PeriodicalId":23812,"journal":{"name":"Xenobiotica","volume":" ","pages":"132-139"},"PeriodicalIF":1.2,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145906406","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}
引用次数: 0
The mitochondrial protective mechanisms mediated by SGLT2i: from molecular basis to clinical implications. SGLT2i介导的线粒体保护机制:从分子基础到临床意义
IF 1.2 4区 医学
Xenobiotica Pub Date : 2026-02-01 Epub Date: 2026-01-12 DOI: 10.1080/00498254.2026.2613138
Jianing Chen, Fengqi Wan, Kaiyue Wu, Xinling Xie, Tingting Wu
{"title":"The mitochondrial protective mechanisms mediated by SGLT2i: from molecular basis to clinical implications.","authors":"Jianing Chen, Fengqi Wan, Kaiyue Wu, Xinling Xie, Tingting Wu","doi":"10.1080/00498254.2026.2613138","DOIUrl":"10.1080/00498254.2026.2613138","url":null,"abstract":"<p><p>SGLT2 inhibitors(SGLT2i) inhibit glucose reabsorption in renal proximal tubules, promote urinary glucose excretion, and lower blood glucose. They also protect cardiovascular, renal, and nervous systems, though mechanisms remain unclear.Mitochondria are key organelles for energy metabolism, redox balance, and calcium regulation, playing a critical role in chronic disease pathogenesis and progression.SGLT2i improve mitochondrial function by enhancing quality control, modulating energy metabolism, strengthening antioxidant defenses, and maintaining calcium homeostasis.These mitochondria-centered mechanisms may underlie SGLT2i protection of cardiovascular, renal, and neurological systems. This review summarizes these effects and discusses therapeutic implications.</p>","PeriodicalId":23812,"journal":{"name":"Xenobiotica","volume":" ","pages":"140-152"},"PeriodicalIF":1.2,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145913124","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}
引用次数: 0
Fluorescent dyes as functional probes for studying drug-transporting solute carriers. 荧光染料作为研究药物运输溶质载体的功能探针。
IF 1.5 4区 医学
Xenobiotica Pub Date : 2026-02-01 Epub Date: 2026-01-21 DOI: 10.1080/00498254.2026.2616247
Olivier Fardel, Amélie Moreau, Hélène Le Mentec, Claire Denizot, David Malnoë, Yannick Parmentier
{"title":"Fluorescent dyes as functional probes for studying drug-transporting solute carriers.","authors":"Olivier Fardel, Amélie Moreau, Hélène Le Mentec, Claire Denizot, David Malnoë, Yannick Parmentier","doi":"10.1080/00498254.2026.2616247","DOIUrl":"10.1080/00498254.2026.2616247","url":null,"abstract":"<p><p>Solute carrier (SLC) transporters are key players in drug pharmacokinetics and are notably involved in drug-drug interactions; their potential interactions with new molecular entities must be evaluated during pharmaceutical development for regulatory purposes.Various fluorescent probes substrates for SLCs have been characterised. This review summarises the nature of these dyes and their application <i>in vitro</i> for investigating interactions between drugs or other chemicals and main 'regulatory' SLCs that handle anionic or cationic compounds. The advantages and limitations of using fluorescent probes for SLC studies are discussed.Fluorescent probe-based SLC assays enable the identification and characterisation of xenobiotic-mediated inhibition of SLC activity through <i>cis</i>-inhibition assays. They also facilitate the study of fundamental properties, polymorphisms, and regulatory pathways of SLCs, as well as the characterisation of SLC substrates <i>via trans</i>-stimulation or competitive counterflow assays.Dye-based SLC activity assays are more cost-effective and less labour-intensive than conventional methods relying on radiolabeled substrates or liquid chromatography-tandem mass spectrometry. They are also fully compatible with high-throughput screening.Limitations of fluorescent dye-based SLC assays include the relatively low specificity of fluorescent probes, substrate-dependent variability in SLC inhibition, and limited performance of <i>trans</i>-stimulation or competitive counterflow assays for identifying SLC substrates.</p>","PeriodicalId":23812,"journal":{"name":"Xenobiotica","volume":" ","pages":"105-120"},"PeriodicalIF":1.5,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145949153","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}
引用次数: 0
Impact of Terminalia ivorensis on drug metabolising and antioxidant enzyme activities, hepatotoxicity and genotoxicity in human liver cells in vitro. 鸢尾对体外人肝细胞药物代谢、抗氧化酶活性、肝毒性和遗传毒性的影响。
IF 1.5 4区 医学
Xenobiotica Pub Date : 2026-02-01 Epub Date: 2026-02-16 DOI: 10.1080/00498254.2026.2623069
Aliu Moomin, Rachel M Knott, Wendy R Russell, Susan J Duthie
{"title":"Impact of <i>Terminalia ivorensis</i> on drug metabolising and antioxidant enzyme activities, hepatotoxicity and genotoxicity in human liver cells <i>in vitro</i>.","authors":"Aliu Moomin, Rachel M Knott, Wendy R Russell, Susan J Duthie","doi":"10.1080/00498254.2026.2623069","DOIUrl":"10.1080/00498254.2026.2623069","url":null,"abstract":"<p><p>We previously reported the effects of <i>Terminalia ivorensis</i> on the proliferation, genomic instability and migration of human colon cancer cells. This study assessed the effect of <i>T. ivorensis</i> on hepatotoxicity, genotoxicity and drug metabolising and antioxidant enzymes (DMAEs) in human liver which remains unknown.<i>T. ivorensis</i> sample was extracted sequentially with petroleum ether (TIPE), chloroform (TICE), ethyl acetate (TIEaE) and ethanol (TIEE) and the phytochemicals analysed. Effects of <i>T. ivorensis</i> extracts on HepG2 cell viability and growth, and DNA damage, and the activities of DMAEs were investigated.<i>T. ivorensis</i> extracts decreased cell viability, cell growth and increased DNA damage (IC<sub>50</sub> ≥3.5 mg/ml for viability and growth; and LC<sub>50</sub>=1.1-2 mg/ml DNA damage). TIEE was both the most cytotoxic (IC<sub>50</sub>=1.6 mg/ml) and genotoxic (LC<sub>50</sub>=1.1 mg/ml). TICE significantly (<i>p</i> < 0.05) inhibited the activities of cytochrome P450, reduced glutathione (GSH), glutathione peroxidase (GPx) and glutathione reductase (GSR). TIEE significantly (<i>p</i> < 0.05) induced the activities of cytochrome P450, catalase, GSH, GPx and GSR.<i>T. ivorenesis</i> extracts were equally cyto- and genotoxic to human liver cells at high concentrations and were well-tolerated at lower concentrations. <i>T. ivorensis</i> also showed a significant and differential time-dependent ability to alter several key DMAEs which may impact subsequent metabolism in human liver.</p>","PeriodicalId":23812,"journal":{"name":"Xenobiotica","volume":" ","pages":"153-163"},"PeriodicalIF":1.5,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146202648","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}
引用次数: 0
Apigenin derivatives as promising norovirus RdRp inhibitors: insights from in silico docking and molecular dynamics studies. 芹菜素衍生物作为有前途的诺如病毒RdRp抑制剂:来自硅对接和分子动力学研究的见解。
IF 1.2 4区 医学
Xenobiotica Pub Date : 2026-02-01 Epub Date: 2026-01-22 DOI: 10.1080/00498254.2025.2566212
M D Sanober, Estari Mamidala
{"title":"Apigenin derivatives as promising norovirus RdRp inhibitors: insights from <i>in silico</i> docking and molecular dynamics studies.","authors":"M D Sanober, Estari Mamidala","doi":"10.1080/00498254.2025.2566212","DOIUrl":"10.1080/00498254.2025.2566212","url":null,"abstract":"<p><p>Norovirus is a leading cause of acute gastroenteritis worldwide, yet no approved antivirals currently exist.In this study, we employed <i>in silico</i> approaches to evaluate apigenin derivatives as potential inhibitors of norovirus RNA-dependent RNA polymerase (RdRp). Seventy-three compounds were initially retrieved from the ZINC database, of which 36 satisfied Lipinski's Rule of Five and were advanced for detailed analysis.Pharmacokinetic predictions revealed high intestinal absorption and favourable drug-likeness profiles for most derivatives, with limited central nervous system penetration, desirable for targeting gastrointestinal infections.Molecular docking identified ZINC14636470 (A1) as the top candidate with strong binding affinity (-9.9 kcal/mol) and key hydrogen bond interactions at the RdRp active site.Molecular dynamics simulations confirmed the stability of the A1-RdRp complex (RMSD = 0.20 ± 0.03 nm; Rg = 2.39 ± 0.02 nm).While AMES predictions flagged some derivatives as potentially mutagenic, scaffold optimisation may mitigate these risks. Apigenin derivatives, particularly A1, demonstrate promising inhibitory potential against norovirus RdRp, combining favourable pharmacokinetic properties with stable enzyme binding. These findings provide a computational foundation for subsequent <i>in vitro</i> and <i>in vivo</i> validation, supporting the development of natural flavonoid-based scaffolds as antiviral leads against norovirus.</p>","PeriodicalId":23812,"journal":{"name":"Xenobiotica","volume":" ","pages":"121-131"},"PeriodicalIF":1.2,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145151196","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}
引用次数: 0
Protective effect of carvacrol in a cardiac myoblast cell model of myocardial ischaemia-reperfusion injury. carvacrol对心肌缺血再灌注损伤成肌细胞模型的保护作用。
IF 1.2 4区 医学
Xenobiotica Pub Date : 2026-01-01 Epub Date: 2025-12-01 DOI: 10.1080/00498254.2025.2567470
Ali M Albarrati, Rakan I Nazer
{"title":"Protective effect of carvacrol in a cardiac myoblast cell model of myocardial ischaemia-reperfusion injury.","authors":"Ali M Albarrati, Rakan I Nazer","doi":"10.1080/00498254.2025.2567470","DOIUrl":"10.1080/00498254.2025.2567470","url":null,"abstract":"<p><p>Phytopharmacology has become a key approach for developing new therapeutic strategies by utilising the diverse bioactive properties of plant-derived compounds to treat complex diseases, including cardiovascular disorders. Myocardial ischaemia-reperfusion (I/R) injury presents a major challenge in the management of acute myocardial infarction by worsening myocardial damage through oxidative stress, apoptosis, and cellular senescence. Carvacrol, a monoterpenoid phenol present in plants such as <i>Origanum vulgare</i>, possesses potent antioxidant and anti-inflammatory properties. This study investigates carvacrol's cardioprotective effects in an H9C2 cardiac myoblast model of I/R injury.Cardiac myoblast cells were exposed to an ischaemic buffer to simulate I/R conditions, with carvacrol administered at a sub-cytotoxic dose of 12.5 µg/mL prior to exposure. Carvacrol significantly enhanced cell viability by 77.37% restoration, reduced lactate dehydrogenase (LDH) release (from 330.5 ± 25.3 to 160.8 ± 15.7 U/mL, <i>p</i> < 0.01), suppressed reactive oxygen species (ROS) production, inhibited caspase-3 and -8 activities, and mitigated cellular senescence as evidenced by reduced β-galactosidase staining. Additionally, carvacrol restored the expression of the myogenin gene, which was downregulated by ischaemic injury.These findings highlight carvacrol's antioxidant, anti-apoptotic, anti-senescence, and gene-regulatory properties, positioning it as a promising therapeutic candidate for mitigating myocardial I/R injury.</p>","PeriodicalId":23812,"journal":{"name":"Xenobiotica","volume":" ","pages":"44-52"},"PeriodicalIF":1.2,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145201764","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}
引用次数: 0
Effects of different doses of dexmedetomidine combined with stellate ganglion block in patients undergoing laparoscopic radical resection of colorectal cancer. 不同剂量右美托咪定联合星状神经节阻滞在腹腔镜大肠癌根治术中的作用。
IF 1.2 4区 医学
Xenobiotica Pub Date : 2026-01-01 Epub Date: 2026-01-19 DOI: 10.1080/00498254.2025.2612029
Liang Sun, Lin Jiang, Zheng Gu, Pengfei Zhao, Dong Xiang, Jinyu Man, Longjiang Wang, Yue Shi
{"title":"Effects of different doses of dexmedetomidine combined with stellate ganglion block in patients undergoing laparoscopic radical resection of colorectal cancer.","authors":"Liang Sun, Lin Jiang, Zheng Gu, Pengfei Zhao, Dong Xiang, Jinyu Man, Longjiang Wang, Yue Shi","doi":"10.1080/00498254.2025.2612029","DOIUrl":"10.1080/00498254.2025.2612029","url":null,"abstract":"<p><p>We aimed to expound the effects of different doses of dexmedetomidine (Dex) combined with stellate ganglion block (SGB) on postoperative pain, sleep quality, and serum orexin A levels in patients undergoing general anaesthesia for laparoscopic radical resection for colorectal cancer (CRC).This prospective randomised controlled trial enrolled 320 CRC patients, randomly assigned to four groups (<i>n</i> = 80): control (0.9% NaCl + SGB), and three Dex groups receiving low, medium, or high Dex infusion (0.2, 0.4, and 0.6 µg/kg·h, respectively) combined with SGB. Postoperative pain [Visual Analogue Scale (VAS), postoperative days 1-3], insomnia [Athens Insomnia Scale (AIS), before and after surgery], serum orexin-A levels (enzyme-linked immunosorbent assay), and adverse events were assessed and compared.All Dex groups showed lower VAS scores (postoperative days 1-3), postoperative AIS scores, and serum orexin-A levels than the control group (<i>p</i> < 0.05). These improvements were dose-dependent, with the high-dose group demonstrating the most significant effects. The incidence of adverse events was lower in the Dex groups, with no significant differences across dosage levels (<i>p</i> > 0.05).Dex at 0.6 µg/kg·h combined with SGB provides optimal postoperative analgesia, improves sleep quality, lowers serum orexin-A, and does not significantly increase adverse events.</p>","PeriodicalId":23812,"journal":{"name":"Xenobiotica","volume":" ","pages":"98-104"},"PeriodicalIF":1.2,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145901154","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}
引用次数: 0
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