Xenobiotica最新文献_第4页

In silico analysis of nicotine's molecular targets in Parkinson's disease. 帕金森病中尼古丁分子靶点的计算机分析。

IF 1.2 4区医学

Xenobiotica Pub Date : 2025-05-01 Epub Date: 2025-06-24 DOI: 10.1080/00498254.2025.2519826

Hai Duc Nguyen

{"title":"In silico analysis of nicotine's molecular targets in Parkinson's disease.","authors":"Hai Duc Nguyen","doi":"10.1080/00498254.2025.2519826","DOIUrl":"10.1080/00498254.2025.2519826","url":null,"abstract":"We aimed to elucidate the molecular processes involved in how nicotine affects PD.Toxicogenomic, molecular mechanisms, physicochemical properties, pharmacokinetic profile, and biological activity were analysed.We found that the therapeutic potential of nicotine in PD may be attributed to its ability to modulate the expression of 38 genes, especially GAPDH, TNF, IL6, and BDNF. The molecular mechanisms underlying the protective effects of nicotine against PD involve several pathways, including the 'Parkinson's disease pathway', 'the selenium micronutrient network', 'the oxidative stress response', 'dopamine binding', 'Parkinsonian disorders', and 'Lewy body disease'. miRNAs like hsa-miRNA-203a-3p and miRNA-26b-5p and transcription factors like HNF4, MAPK3, and EVI1 explained how nicotine protects neurons from PD.An assessment was also carried out on drug candidates (polaprezinc) and miRNA sponges (hsa-miR-181a-5p, hsa-miR-124-3p, hsa-miR-1-3p) that may possess the capability to synergize the effects of nicotine. Nicotine's physicochemical properties, pharmacokinetic profile, and biological activity are conducive to its favourable attributes in the context of PD, including high gastrointestinal absorption, ability to penetrate the blood-brain barrier, non-P-glycoprotein nature, and antiparkinsonian effects.Nicotine plays crucial roles in the pathophysiology of PD. Further work is needed to evaluate the impact of nicotine on non-motor symptoms.","PeriodicalId":23812,"journal":{"name":"Xenobiotica","volume":" ","pages":"397-423"},"PeriodicalIF":1.2,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144326999","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

Beta-aminoisobutyric acid attenuates doxorubicin-induced cardiotoxicity through the adenosine 5'-monophosphate-activated protein kinase-mediated pathway. β -氨基异丁酸通过腺苷5'-单磷酸活化蛋白激酶介导的途径减弱阿霉素诱导的心脏毒性。

IF 1.3 4区医学

Xenobiotica Pub Date : 2025-05-01 Epub Date: 2025-06-23 DOI: 10.1080/00498254.2025.2520423

Jietao Huang, Mao Sun, Jing Yu, Yihong Guo, Baoshan Li, Linyan Dai, Yangyang Tang, Xingsheng Wang, Shubo Han, Xia Lai

{"title":"Beta-aminoisobutyric acid attenuates doxorubicin-induced cardiotoxicity through the adenosine 5'-monophosphate-activated protein kinase-mediated pathway.","authors":"Jietao Huang, Mao Sun, Jing Yu, Yihong Guo, Baoshan Li, Linyan Dai, Yangyang Tang, Xingsheng Wang, Shubo Han, Xia Lai","doi":"10.1080/00498254.2025.2520423","DOIUrl":"10.1080/00498254.2025.2520423","url":null,"abstract":"In this study, the adenosine 5'-monophosphate-activated protein kinase (AMPK)-dependent mechanisms underlying the effect of β-aminoisobutyric acid (BAIBA), an exercise-induced myokine, in mitigating doxorubicin (DOX)-induced cardiotoxicity were investigated.In vitro/vivo DOX-induced injury models were constructed, and their cardiac functions were detected by echocardiography/histology. Moreover, serum biomarkers including lactate dehydrogenase (LDH), creatine kinase-myocardial band (CK-MB), and brain natriuretic peptide (BNP) were measured. The mitochondrial ultrastructure was examined by transmission electron microscopy (TEM), and the generation of reactive oxygen species (ROS) was checked by MitoSOX™ Red staining. The analysis results showed that BAIBA significantly preserved the cardiac systolic function, reduced myocardial damage, and attenuated mitochondrial dysfunction, as evidenced by maintained cristae integrity and suppressed ROS overproduction. The mechanism was that BAIBA enhanced cardiac AMPK phosphorylation, while dorsomorphin abrogated the antioxidant effects of AMPK through inhibiting its activation.The findings demonstrate that BAIBA counteracts DOX cardiotoxicity via AMPK-mediated mitochondrial bioenergetic preservation. It provides a novel cardioprotective therapy as an exercise-mimetic adjuvant.","PeriodicalId":23812,"journal":{"name":"Xenobiotica","volume":" ","pages":"436-443"},"PeriodicalIF":1.3,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144318121","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

Formulation of apigenin-loaded solid lipid nanoparticles: characterisation, molecular docking, and anticancer assay. 芹菜素负载固体脂质纳米颗粒的配方：表征，分子对接和抗癌测定。

IF 1.3 4区医学

Xenobiotica Pub Date : 2025-04-01 Epub Date: 2025-06-22 DOI: 10.1080/00498254.2025.2517113

Sadaf Jamal Gilani, Najla Altwaijry, Ahlam Mansour Sultan, Reem Basoudan, Reem Albesher, Kaneez Fatima

{"title":"Formulation of apigenin-loaded solid lipid nanoparticles: characterisation, molecular docking, and anticancer assay.","authors":"Sadaf Jamal Gilani, Najla Altwaijry, Ahlam Mansour Sultan, Reem Basoudan, Reem Albesher, Kaneez Fatima","doi":"10.1080/00498254.2025.2517113","DOIUrl":"10.1080/00498254.2025.2517113","url":null,"abstract":"1. Apigenin (APN), a natural flavonoid, showed strong therapeutic potential against skin cancer, but its clinical use is restricted due to its complex physicochemical characteristics.2. Hence, this study aimed to fabricate APN-loaded solid lipid nanoparticles (APN-SLNs) for improved topical treatment of skin cancer. The developed APN-SLNs were evaluated for particle characterization, compatibility and crystallinity by employing FT-IR, DSC, and XRD. The selected APN-SLNs-loaded hydrogels further evaluated for gel evaluation, permeation and cytotoxicity assessment. The findings also supported with molecular docking study.3. The developed APN-SLNs demonstrated nanometric size, low polydispersity index, negative surface charge, high encapsulation efficiency and a biphasic release profile. The developed APN-SLNs-loaded hydrogels represented comparatively higher viscosity, firmness, consistency, and cohesiveness compared with the pure APN-loaded hydrogels. The APN-SLNs-loaded hydrogels represented >2 times higher in vitro permeation than pure APN-loaded hydrogels. Further, MTT assay using B16-F10 melanoma cells revealed the superior cytotoxic potential of the developed nanocarrier than the native counterpart. The docking study also supports the findings of the cell viability assay with a high docking score.4. Therefore, this study suggests that topical delivery of APN encapsulated in SLNs is a promising approach for skin cancer management.","PeriodicalId":23812,"journal":{"name":"Xenobiotica","volume":" ","pages":"283-295"},"PeriodicalIF":1.3,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144267401","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

Quantitative prediction of drug-drug interactions arising from CYP3A4 induction using chimeric mice with humanized liver. 人源化肝脏嵌合小鼠诱导CYP3A4引起的药物相互作用的定量预测。

IF 1.3 4区医学

Xenobiotica Pub Date : 2025-04-01 Epub Date: 2025-06-18 DOI: 10.1080/00498254.2025.2518239

Keigo Nakayama, Tamotsu Negoro, Hiroaki Takubo, Asami Hayashi, Toshio Taniguchi, Yukihiro Nomura, Kazunori Iwanaga

{"title":"Quantitative prediction of drug-drug interactions arising from CYP3A4 induction using chimeric mice with humanized liver.","authors":"Keigo Nakayama, Tamotsu Negoro, Hiroaki Takubo, Asami Hayashi, Toshio Taniguchi, Yukihiro Nomura, Kazunori Iwanaga","doi":"10.1080/00498254.2025.2518239","DOIUrl":"10.1080/00498254.2025.2518239","url":null,"abstract":"We aimed to establish an approach to quantitatively predict drug-drug interactions arising from cytochrome P450 (CYP) 3A4 induction using chimeric mice with humanised liver.After repeated administration of rifampicin or efavirenz as CYP inducers to chimeric mice, the relative expression of human CYP3A4 in their livers was measured and plotted against the area under the concentration-time curve (AUC) of rifampicin and efavirenz, respectively, in plasma on the final day of administration. Induction curves were obtained by fitting the plots.Assuming a similar relationship of relative CYP3A4 expression to AUC in chimeric mice as in humans, the relative CYP3A4 expression by clinical doses of rifampicin and efavirenz were calculated from the estimated clinical exposure.The calculated relative CYP3A4 expression was reflected in the intrinsic clearance of midazolam or alfentanil coadministered with a CYP inducer. The intrinsic clearance was incorporated into a constructed physiologically based pharmacokinetic model, which successfully predicted the pk change of midazolam or alfentanil coadministered with a CYP inducer or not. The results confirmed that our approach is useful to improve the prediction accuracy of CYP3A4 induction in the preclinical phase.","PeriodicalId":23812,"journal":{"name":"Xenobiotica","volume":" ","pages":"317-328"},"PeriodicalIF":1.3,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144276144","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

Meeting report: DMDG peptide and oligonucleotide ADME workshop 2024. 会议报告：DMDG肽和寡核苷酸ADME研讨会2024。

IF 1.3 4区医学

Xenobiotica Pub Date : 2025-04-01 Epub Date: 2025-05-28 DOI: 10.1080/00498254.2025.2506702

Inga Bjørnsdottir, Ralf Lotz, Bo Lindmark, Steve Hood, Jesper Kammersgaard Christensen

引用次数: 0

Nano-pharmacokinetics and pharmacodynamics of green-synthesized ZnO nanoparticles: a pathway to safer therapeutic applications. 绿色合成ZnO纳米颗粒的纳米药代动力学和药效学：通往更安全治疗应用的途径。

IF 1.3 4区医学

Xenobiotica Pub Date : 2025-04-01 Epub Date: 2025-05-21 DOI: 10.1080/00498254.2025.2505062

Aishwarya Jain, Kiran Bhise

引用次数: 0

The orexin 1-selective receptor antagonist nivasorexant is a time-dependent inhibitor of CYP2C19 and CYP3A4. 食欲素1选择性受体拮抗剂nivasorexant是一种时间依赖性的CYP2C19和CYP3A4抑制剂。

IF 1.3 4区医学

Xenobiotica Pub Date : 2025-04-01 Epub Date: 2025-06-08 DOI: 10.1080/00498254.2025.2513321

Alexander Treiber, Fabienne Drouet, Swen Seeland, Florian Willecke, Jodi T Williams, Hamed Aissaoui, Benjamin Berger, Stephane Delahaye

{"title":"The orexin 1-selective receptor antagonist nivasorexant is a time-dependent inhibitor of CYP2C19 and CYP3A4.","authors":"Alexander Treiber, Fabienne Drouet, Swen Seeland, Florian Willecke, Jodi T Williams, Hamed Aissaoui, Benjamin Berger, Stephane Delahaye","doi":"10.1080/00498254.2025.2513321","DOIUrl":"10.1080/00498254.2025.2513321","url":null,"abstract":"Nivasorexant was the first orexin 1-selective receptor antagonist entering into clinical development as an exploratory treatment for eating disorders.Drug-drug interactions were observed with markers of CYP2C9, CYP2C19, and CYP3A4. While the interaction with CYP2C19 was expected based on in vitro inhibition data, standard P450 inhibition screening assays according to regulatory guidelines failed to predict the interactions with CYP2C9 and CYP3A4.Mechanistic studies on the circulating metabolites of nivasorexant revealed a heterogeneous picture for the three P450 enzymes with covalent binding as a common denominator. For CYP3A4, the secondary didehydromorpholine metabolite M30 was identified as the major origin for enzyme inactivation. Epoxidation of its double bond might yield a bicyclic reactive metabolite which subsequently binds within the CYP3A4 active site.Nivasorexant and virtually all its circulating metabolites were strong competitive or time-dependent inhibitors of CYP2C19. Some of them are initially produced by CYP3A4 and only exert their inhibitory potential after diffusion into the CYP2C19 active site. CYP2C9 and CYP2C19 both produce the 6-hydroxymorpholine metabolite M25, which exists in equilibrium with its open-chain amino aldehyde form. The latter is chemically reactive and might at least in part explain the covalent binding of nivasorexant to both P450 enzymes.","PeriodicalId":23812,"journal":{"name":"Xenobiotica","volume":" ","pages":"296-305"},"PeriodicalIF":1.3,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144192269","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

Arctigenin-induced erythrocyte membrane remodelling is mediated through calcium influx, metabolic collapse, and casein kinase 1α. 牛蒡子素诱导的红细胞膜重构是通过钙内流、代谢衰竭和酪蛋白激酶1α介导的。

IF 1.3 4区医学

Xenobiotica Pub Date : 2025-04-01 Epub Date: 2025-06-04 DOI: 10.1080/00498254.2025.2513324

Mohammad A Alfhili, Rahaf F Alothaimeen, Jawaher Alsughayyir

{"title":"Arctigenin-induced erythrocyte membrane remodelling is mediated through calcium influx, metabolic collapse, and casein kinase 1α.","authors":"Mohammad A Alfhili, Rahaf F Alothaimeen, Jawaher Alsughayyir","doi":"10.1080/00498254.2025.2513324","DOIUrl":"10.1080/00498254.2025.2513324","url":null,"abstract":"Conclusive evidence suggests that arctigenin (AGN) holds great promise in anticancer therapy but a common and poorly understood complication of chemotherapy is anaemia which is precipitated by eryptosis and haemolysis. This study examines the cytotoxicity of AGN in RBCs.Eryptosis markers including intracellular calcium, phosphatidylserine (PS) externalisation, and cell shrinkage were detected by flow cytometry using Fluo4/AM, annexin-V-FITC, and forward light scatter, respectively. Membrane blebbing was examined using electron microscopy, and photometric and potentiometric methods were used to assay haemolytic markers including haemoglobin, potassium, AST, and LDH.AGN significantly increased Fluo4- and annexin-V-positive cells and decreased forward light scatter which was associated with membrane blebs. While PS externalisation and cell shrinkage were inhibited by extracellular calcium exclusion, suppression of haemolysis required both calcium exclusion and restriction of potassium efflux. Moreover, sucrose and mannitol rescued the cells from haemolysis while exacerbating PS externalisation, which was rather significantly blunted by guanosine and CK1α inhibitor D4476.AGN promotes calcium-dependent eryptosis through energy depletion and CK1α activation, and exhibits a potent haemolytic activity through dysregulated ion trafficking and osmotic stress. These findings underscore the hematological toxicity of AGN and identify potential inhibitors which inform future animal studies and clinical trials.","PeriodicalId":23812,"journal":{"name":"Xenobiotica","volume":" ","pages":"306-316"},"PeriodicalIF":1.3,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144192268","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

Feature-based molecular networking updates the in vitro metabolic characterisation of fenbendazole across species. 基于特征的分子网络更新了芬苯达唑跨物种的体外代谢特征。

IF 1.3 4区医学

Xenobiotica Pub Date : 2025-03-01 Epub Date: 2025-05-04 DOI: 10.1080/00498254.2025.2497047

Young-Heun Jung, Dong-Cheol Lee, Bo-Hyun Choi, Junyoung O Park, Ju-Hyun Kim

{"title":"Feature-based molecular networking updates the in vitro metabolic characterisation of fenbendazole across species.","authors":"Young-Heun Jung, Dong-Cheol Lee, Bo-Hyun Choi, Junyoung O Park, Ju-Hyun Kim","doi":"10.1080/00498254.2025.2497047","DOIUrl":"10.1080/00498254.2025.2497047","url":null,"abstract":"Feature-based molecular networking (FBMN), an advanced metabolomics tool leveraging MS/MS spectral similarity, was applied to update metabolite characterisation of fenbendazole (FBZ), a veterinary antiparasitic agent with emerging anticancer potential in humans. Despite its therapeutic promise, FBZ's human metabolic pathways remain poorly understood.In this study, FBMN was utilised for the comprehensive in vitro profiling of FBZ metabolites across species, employing high-resolution liquid chromatography-mass spectrometry (LC-HRMS) with data-dependant MS2 acquisition.Nine metabolites, including two novel sulphate-conjugated forms (M2 sulphate and M7 sulphate), were identified and structurally characterised through integrated FBMN analysis. Oxidative metabolites (M1-M4) were found to be more abundant in rat liver microsomes, whereas monkey hepatocytes exhibited higher levels of most metabolites. Notably, hydrolysed FBZ (M5) dominated human samples, accounting for the largest proportion in both liver microsomes and hepatocytes, suggesting species-specific enzymatic activity.The application of FBMN provided an enhanced, systematic approach for metabolite identification and inter-species comparison, revealing critical metabolic differences that support FBZ biotransformation. These findings offer novel insights into FBZ's metabolic pathways, supporting its safety and efficacy assessment for potential human therapeutic applications.","PeriodicalId":23812,"journal":{"name":"Xenobiotica","volume":" ","pages":"167-175"},"PeriodicalIF":1.3,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144050519","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

Regulatory effect of atorvastatin combined with berberine on PI3K/AKT/FoxO1 signaling pathway in rats with hyperlipidaemia. 阿托伐他汀联合小檗碱对高脂血症大鼠PI3K/Akt/ fox01信号通路的调控作用

IF 1.3 4区医学

Xenobiotica Pub Date : 2025-03-01 Epub Date: 2025-05-12 DOI: 10.1080/00498254.2025.2503359

Chao Yu, Weihong Yin, Jiao Li, Fan Wu, Siwen Wang, Zhaoyang Han, Haoliang Chen, Xueying Yan, Mingyu Cui

{"title":"Regulatory effect of atorvastatin combined with berberine on PI3K/AKT/FoxO1 signaling pathway in rats with hyperlipidaemia.","authors":"Chao Yu, Weihong Yin, Jiao Li, Fan Wu, Siwen Wang, Zhaoyang Han, Haoliang Chen, Xueying Yan, Mingyu Cui","doi":"10.1080/00498254.2025.2503359","DOIUrl":"10.1080/00498254.2025.2503359","url":null,"abstract":"Atorvastatin Calcium (AC) is the first line lipid-lowering drug in clinical. Nowadays, the combination of AC and BBR is often used to treat hyperlipidaemia in clinical. In order to determine the mechanism, we investigate the regulatory of atorvastatin combined with berberine on PI3K/Akt/FoxO1 signalling pathway in rats with hyperlipidaemia.The hyperlipidaemia rat model was constructed. Meanwhile, lipid-lowering and liver protective effects were determined by oil red O and H&E method. The expression of PI3K, Akt and FoxO1 was examined by IHC, WB and RT-pCR. The level of CK and LDH in serum was examined by ELISA.The results showed that the expression of PI3K, AKT increased and FoxO1 decreased in MC group compared with NC group (p < 0.01). The expression of PI3K, AKT decreased and FoxO1 increased compared with MC group (p < 0.05). The expression of FoxO1 in combination group is lower than AC group. The levels of CK and LDH in AC group increased compared with NC group (p < 0.01), but decreased significantly in AC+BBR group compared with AC group (p < 0.01).The combination of AC and BBR could regulate the lipid level by mediating PI3K/Akt/FoxO1, which is providing new references for the treatment of hyperlipidaemia.","PeriodicalId":23812,"journal":{"name":"Xenobiotica","volume":" ","pages":"256-263"},"PeriodicalIF":1.3,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144050899","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