Journal of pharmaceutical and biomedical analysis最新文献

{"title":"Optimization of GC-MS run time for untargeted metabolomics: Trade-offs between speed, coverage, and repeatability","authors":"Özge Cansın Zeki,&nbsp;Cemil Can Eylem,&nbsp;Emirhan Nemutlu","doi":"10.1016/j.jpba.2025.117068","DOIUrl":"10.1016/j.jpba.2025.117068","url":null,"abstract":"<div><div>Optimizing run time in gas chromatography–mass spectrometry (GC-MS) based metabolomics is essential for balancing metabolite coverage, reproducibility, and practical workflow constraints. In this study, three GC-MS methods with different run times, short (26.7 min), a standard method based on the established Fiehn protocol (37.5 min), and long (60 min), were evaluated across three biological matrices: cell culture, plasma, and urine. All methods were applied using identical injection volumes and derivatization protocols. The number of annotated metabolites in the short and standard methods was comparable: 138 vs. 156 in cell culture, 147 vs. 168 in plasma, and 186 vs. 198 in urine. The long method provided higher metabolite coverage (196 in cell culture, 175 in plasma, 244 in urine), largely due to improved chromatographic resolution and deconvolution, which also increased the number of unannotated features. Although the proportion of high-filling (0.75–1) annotated metabolites was similar across all methods (∼79–90 %), repeatability was slightly better in the standard and long methods (RSD ∼20–24 %) than in the short method (RSD ∼23–30 %). Notably, since derivatized samples must be analyzed within 24 h, the short method presents a practical advantage by enabling completion of full batch analysis within this time constraint. Overall, while the short and standard methods offer similar identification performance, the long method enhances analytical depth.</div></div>","PeriodicalId":16685,"journal":{"name":"Journal of pharmaceutical and biomedical analysis","volume":"266 ","pages":"Article 117068"},"PeriodicalIF":3.1,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144724212","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comprehensive analysis of the in vivo and in vitro metabolism of Guishao Yigong Decoction based on UPLC-Q-TOF/MS","authors":"Wenwen Zhou,&nbsp;Xiaoxiao Zhang,&nbsp;Meijuan Liu,&nbsp;Meiyu Wan,&nbsp;Shu Jiang,&nbsp;Erxin Shang,&nbsp;Jinao Duan","doi":"10.1016/j.jpba.2025.117066","DOIUrl":"10.1016/j.jpba.2025.117066","url":null,"abstract":"<div><div>Guishao Yigong Decoction (GYD), a classic prescription that tonifies the spleen and qi, has been used in clinical practices for thousands of years to treat spleen deficiency. However, its <em>in vitro</em> and <em>in vivo</em> metabolic characteristics are still unclear. In this study, a rapid and reliable analytical method based on ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS) with automated data processing (MetaboLynx) was established to investigate the metabolites and metabolic pathways of GYD <em>in vivo</em> and <em>in vitro</em>. Based on the characteristics of protonated ions, eleven precursors (ginsenoside Re, ginsenoside Rg1, ginsenoside Rb1, atractylenolide I, atractylenolide III, paeoniflorin, glycyrrhizic acid, pachymic acid, liquiritin, nobiletin, and ferulic acid) and their corresponding metabolites were detected and tentatively identified. A total of 81 metabolites were identified, including 53 metabolites <em>in vivo</em>, 40 metabolites of liver microsomes, and 43 metabolites of intestinal flora <em>in vitro</em>. Distinct metabolic patterns were observed between intestinal flora and liver microsomes - the former primarily catalyzed phase I transformations (hydroxylation, methylation, dehydroxylation, demethylation, and reduction), while the latter also executed phase II metabolism, with glucuronidation being the predominant conjugation reaction. The metabolic profiling and pathways of active components in GYD were systematically analyzed, which was helpful in clarifying its potential mechanism and clinical application.</div></div>","PeriodicalId":16685,"journal":{"name":"Journal of pharmaceutical and biomedical analysis","volume":"265 ","pages":"Article 117066"},"PeriodicalIF":3.1,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144680749","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Acetylcholinesterase immobilized on MIL-88B-NH2 MOF for rapid screening inhibitors from herbal medicines: Ligand fishing coupled with mass spectrometry","authors":"Erxu Wang,&nbsp;Huiran Zhang,&nbsp;Xiangchuan Li,&nbsp;Lili Geng,&nbsp;Zhen Wang,&nbsp;Airong Chu,&nbsp;Bin Lu,&nbsp;Li Duan","doi":"10.1016/j.jpba.2025.117067","DOIUrl":"10.1016/j.jpba.2025.117067","url":null,"abstract":"<div><div>Alzheimer’s disease (AD) is a common neurodegenerative disease, and is characterized by impaired acetylcholine-mediated neurotransmission. Acetylcholinesterase (AChE) inhibition is a well-established therapeutic strategy for AD. Medicinal plants exhibit multi-target effects, low toxicity, and cost-effectiveness. Therefore, screening AChE inhibitors from botanical sources holds considerable pharmacological potential. In this study, a metal-organic framework was used as a novel support for immobilizing AChE, resulting in the creation of AChE@MIL-88B-NH₂, which served as a tool for screening potential AChE inhibitors. The immobilized enzyme exhibited excellent reusability, stability against pH fluctuations and thermal stress, and resistance to organic solvents. The constructed AChE@MIL-88B-NH₂-based ligand fishing strategy coupled with mass spectrometry was applied to screen for AChE inhibitors in <em>Nelumbinis plumula</em> extracts. Seven compounds were identified as potent AChE inhibitors. Enzyme kinetic assays revealed that these ligands exhibit a mixed inhibition mechanism against AChE. Molecular docking demonstrated that the seven compounds effectively bound to the AChE active site, with binding affinities ranging from −9.7 to −8.5 kcal/mol. The established AChE@MIL-88B-NH₂-based ligand fishing strategy provides a simple and efficient approach for screening potential AChE inhibitors from complex botanical matrices, offering a promising avenue for discovering novel therapeutic agents for AD.</div></div>","PeriodicalId":16685,"journal":{"name":"Journal of pharmaceutical and biomedical analysis","volume":"265 ","pages":"Article 117067"},"PeriodicalIF":3.1,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144680750","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Key targets of brain-gut coordination in Wuzhuyu decoction treating chronic migraine based on proteomics","authors":"Meijing Li ,&nbsp;Zhimin Song ,&nbsp;Keshu Wang ,&nbsp;Qi Wang ,&nbsp;Xiaomeng Guo ,&nbsp;Ziwei Zhou ,&nbsp;Jingjing Xu ,&nbsp;Sha Wu ,&nbsp;Muxin Gong","doi":"10.1016/j.jpba.2025.117064","DOIUrl":"10.1016/j.jpba.2025.117064","url":null,"abstract":"<div><div>Chronic migraine is a debilitating disorder often accompanied by gastrointestinal dysfunction. However, the targets and mechanisms underlying this interaction in migraine remain unclear. Wuzhuyu Decoction (WZYD), a traditional Chinese medicine, has shown efficacy in alleviating migraine and gastrointestinal symptoms. However, its mechanisms of brain-gut coordination remain unclear. This study investigates the mechanisms of WZYD on the brainstem and colon in chronic migraine model rats based on proteomics. A chronic migraine model was induced via meningeal inflammation, followed by WZYD administration. WZYD increased pain thresholds, reduced CGRP and Fos, while elevating 5-HT. Proteomic analysis identified proteins significantly regulated by WZYD in the brainstem and colon respectively, primarily involved in inflammation and signal transduction. UHPLC-Q-Exactive-MS/MS revealed blood-absorbed components of WZYD, and network analysis predicted 959 potential targets. Proteomics-based PPI analysis combined with network analysis of blood-absorbed components identified DDO, PRKACB, and MAPK8 as key potential targets regulated by WZYD. These findings were validated through molecular docking, mRNA and protein expression analysis. WZYD reduced Iba-1, TNF-<em>α</em>, IL-6, SP, DDO, PRKACB, and MAPK8, while elevating IL-10 and GLP-2 levels, mitigating neuroinflammation and intestinal inflammation. These findings suggest WZYD could alleviate chronic migraine by regulating key protein targets and coordinating anti-inflammatory responses in the brain and gut.</div></div>","PeriodicalId":16685,"journal":{"name":"Journal of pharmaceutical and biomedical analysis","volume":"265 ","pages":"Article 117064"},"PeriodicalIF":3.1,"publicationDate":"2025-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144656054","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring the redox mechanism of 9-acridinyl amino acid derivatives by electrochemical and theoretical approach","authors":"Jelena Rupar ,&nbsp;Marija Popović-Nikolić ,&nbsp;Katarina Nikolić ,&nbsp;Vladimir Dobričić ,&nbsp;Olivera Čudina ,&nbsp;Mara M. Aleksić","doi":"10.1016/j.jpba.2025.117062","DOIUrl":"10.1016/j.jpba.2025.117062","url":null,"abstract":"<div><div>Investigating and understanding the redox characteristics of potential anticancer agents is of great importance, as these properties are the key factor in the anticancer potential of drugs and can impact the mechanism of action, stability, metabolism, and selectivity of the drug toward cancer cells. Four compounds, previously confirmed to possess notable <em>in vitro</em> anticancer activity and the ability to interact with DNA, were subjected to a detailed electrochemical study. These are 9-acridinyl amino acid derivatives (9R-A), which were investigated in this study using cyclic voltammetry (CV) and differential pulse voltammetry (DPV) with a glassy carbon electrode. The effects of pH (ranging from pH 2–9) and scan rate were thoroughly examined. The findings revealed that three independent oxidation and reduction processes occurred, all of which were diffusion-controlled. Two electroactive regions of the molecule contribute to these redox processes: the nitrogen (N10) of the acridine ring and the enamine nitrogen (N11) in the derivative’s side chain. In 9R-A, the acridine ring undergoes a two-electron oxidation: first forming a monomeric radical cation that dimerizes, then undergoing a second electron transfer to yield a new radical cation. The reduction mechanism similarly involves a two-electron transfer, producing a monomeric radical that dimerizes and later forms a new radical. A significant factor in the redox behavior of 9-acridinyl amino acid derivatives is the presence of a secondary amine in the side-chain substituent. This amine undergoes oxidation via the loss of a single electron, resulting in the formation of a monomeric radical cation that is stabilized through deprotonation. While the oxidation mechanism appears to be consistent across all four 9R-A derivatives, differences in their oxidation affinity arise due to structural variations in the side-chain substituents. The experimental electrochemical findings were further supported by computational chemistry. Quantum chemical parameter evaluations provide deeper insights into the oxidation and reduction mechanisms, particularly in relation to the influence of substituents on these processes.</div></div>","PeriodicalId":16685,"journal":{"name":"Journal of pharmaceutical and biomedical analysis","volume":"265 ","pages":"Article 117062"},"PeriodicalIF":3.1,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144656053","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Two-phase hollow fiber based liquid phase microextraction using hydrophobic deep eutectic solvents for extraction of trace amounts of benzodiazepines in biological samples","authors":"Mehri Beiranvand,&nbsp;Yadollah Yamini,&nbsp;Mohammad Mahdi Khataei","doi":"10.1016/j.jpba.2025.117061","DOIUrl":"10.1016/j.jpba.2025.117061","url":null,"abstract":"<div><div>This study carefully prepared hydrophobic deep eutectic solvents (H-DESs) for the acceptor phase in two-phase hollow fiber liquid phase microextraction (HF-LPME). This innovative approach was used for the extraction of benzodiazepines from biological samples. H-DESs were synthesized using five different compounds: menthol, choline chloride, lauric acid, decanoic acid, and octanoic acid, which were in specific molar ratios. High-performance liquid chromatography with UV detection was employed to analyze the extracted analytes. Various parameters influencing the extraction efficiency of benzodiazepine were carefully optimized and investigated. Under the optimized conditions, a linear dynamic range of 1–1000 μg/L was achieved with correlation coefficients greater than 0.991. Quantitation limits in the 1–5 μg/L range and detection limits between 0.3 and 1.5 μg/L were obtained. Preconcentration factors in the range of 89–145 were also obtained.</div><div>The method was employed for the extraction and determination of benzodiazepines biological samples, resulting in favorable results.</div></div>","PeriodicalId":16685,"journal":{"name":"Journal of pharmaceutical and biomedical analysis","volume":"265 ","pages":"Article 117061"},"PeriodicalIF":3.1,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144631617","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrated network pharmacology and metabolomics to investigate the effect and mechanism of nitidine chloride against cholangiocarcinoma","authors":"Weian Qiu ,&nbsp;Qianxue Yu ,&nbsp;Yongping He ,&nbsp;Yanqiu Huang ,&nbsp;Diya Lv ,&nbsp;Hui Wang ,&nbsp;Yong Ye ,&nbsp;Zhanying Hong ,&nbsp;Yue Liu","doi":"10.1016/j.jpba.2025.117063","DOIUrl":"10.1016/j.jpba.2025.117063","url":null,"abstract":"<div><div>Cholangiocarcinoma (CCA) is an aggressive malignancy with a poor prognosis. Nitidine chloride (NitC), a bioactive alkaloid derived from <em>Zanthoxylum nitidum</em> (Roxb.) DC., exhibits potential anti-cancer activity against CCA. However, the metabolic mechanism underlying the anti-cancer effect of NitC remains poorly understood and requires further elucidation. This study integrated metabolomics and network pharmacology to systematically investigate the anti-cancer activity and underlying mechanisms of NitC in treating human cholangiocarcinoma cells. First, The effects of NitC on human cholangiocarcinoma cells were assessed by cell proliferation, apoptosis, and cycle. Then, potential mechanisms and targets were investigated using a combination of cell metabolomics and network pharmacology and verified by molecular docking. Finally, we measured the protein levels of potential targets in TFK1 cells using enzyme-linked immunosorbent assay (ELISA). Our results indicated that NitC treatment induced the proliferation inhibition, G2/M arrest and apoptosis of TFK1 cells in a concentration dependent manner. The metabolomics analysis identified forty differential metabolic biomarkers and five key metabolic pathways of NitC in treating CCA. Network pharmacology found 36 potential targets for NitC intervention on CCA. The integration of network pharmacology and metabolomics constructed the “compound-reaction-enzyme-gene” association and revealed that NitC exerts its efficacy on CCA through four key targets, eleven metabolic indicators, and glycine, serine and threonine metabolism, and tyrosine metabolism. Molecular docking further confirmed robust binding interactions between NitC and these key targets. Moreover, ELISA results showed that NitC treatment significantly attenuated the protein levels of PIK3CA, PTGS2, and PRKACA in TFK1 cells. This study demonstrates that combining metabolomics and network pharmacology provides a powerful strategy to elucidate the pharmacological mechanisms of natural compounds, also offering new insights into the therapeutic potential of NitC for CCA.</div></div>","PeriodicalId":16685,"journal":{"name":"Journal of pharmaceutical and biomedical analysis","volume":"265 ","pages":"Article 117063"},"PeriodicalIF":3.1,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144605496","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advancing therapeutic monoclonal antibody analysis: A sequential injection lab-on-valve approach","authors":"Diana R. Cunha,&nbsp;M. Beatriz Quinaz,&nbsp;Marcela A. Segundo","doi":"10.1016/j.jpba.2025.117060","DOIUrl":"10.1016/j.jpba.2025.117060","url":null,"abstract":"<div><div>Advancements in automated flow-based techniques have significantly improved precision, efficiency, and sustainability in the analytical field. Among these, sequential injection lab-on-valve (SI-LOV) offer a miniaturized and resource-efficient approach for high-throughput analysis. In this work, the feasibility of a fully automated SI-LOV system coupled with a miniaturized spectrometer was investigated for therapeutic monoclonal antibodies (mAbs) assessment. Six mAbs, including Rituximab (RTX), Trastuzumab, Cetuximab, Nivolumab, Panitumumab, and Ramucirumab, were analyzed. Quantification of mAbs, particularly RTX, was achieved with high accuracy, linearity (0.25–1.25 mg mL⁻¹, R &gt; 0.996), and low limit of detection (0.09 mg mL⁻¹). Second-order derivative spectroscopy (245–300 nm) enabled qualitative assessment via well-resolved peaks, mainly related to phenylalanine, tyrosine, and tryptophan present in mAb structures. Mass-based calibration, ensuring consistent quantification regardless of calibration by sample concentration or injection volume, was possible for sample mass &gt; 5 µg. The study of SI-LOV parameters ensured good repeatability (1.8 %), reproducibility (2.3 %), and rapid analysis (<em>ca.</em> 110 s per determination). RTX concentration was estimated for a surrogate cell culture supernatant with good accuracy (&gt; 96 %), demonstrating its potential for application in biopharmaceutical workflows for high throughput mAb analysis. These findings highlight the SI-LOV system's effectiveness as a robust and automated platform for mAb analysis, offering significant potential for routine quality control, high-throughput analysis, and process monitoring in the biopharmaceutical industry.</div></div>","PeriodicalId":16685,"journal":{"name":"Journal of pharmaceutical and biomedical analysis","volume":"265 ","pages":"Article 117060"},"PeriodicalIF":3.1,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144631619","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tissue distribution of OL9-116, a Tdp1 inhibitor based on usnic acid, is significantly altered in Lewis lung carcinoma-bearing mice compared to healthy animals","authors":"Alina A. Okhina ,&nbsp;Tatyana E. Kornienko ,&nbsp;Artem D. Rogachev ,&nbsp;Olga A. Luzina ,&nbsp;Nelly A. Popova ,&nbsp;Valery P. Nikolin ,&nbsp;Alexandra L. Zakharenko ,&nbsp;Nadezhda S. Dyrkheeva ,&nbsp;Andrey G. Pokrovsky ,&nbsp;Nariman F. Salakhutdinov ,&nbsp;Olga I. Lavrik","doi":"10.1016/j.jpba.2025.117054","DOIUrl":"10.1016/j.jpba.2025.117054","url":null,"abstract":"<div><div>In the present study, we developed and validated three liquid chromatography–tandem mass spectrometry (LC–MS/MS) methods for quantification of the agent OL9–116, a Tdp1 inhibitor based on usnic acid, in murine lungs, liver and kidney, respectively. Additionally, a semi-quantitative method was developed for quantification of the agent in the primary tumor node of Lewis lung carcinoma. Tissue samples were prepared using ultrasonic homogenization and QuEChERS methodology. The quantification of the compound was performed using SCIEX 6500 QTRAP mass spectrometer in MRM mode following a chromatographic separation on a C8 reversed-phase column. The methods were validated in terms of selectivity, calibration curve, accuracy, precision, recovery, matrix factor and stability of the prepared sample, and subsequently applied for quantification of the agent OL9–116 in the organs of healthy and tumor-bearing mice following a single intragastric administration of the substance at a dose of 150 mg/kg. A comparison of the distribution of OL9–116 in the organs of the animals demonstrated that the presence of the tumor significantly altered the pharmacokinetics of the substance, reducing its bioavailability, which should be taken into account when developing tumor treatment strategies.</div></div>","PeriodicalId":16685,"journal":{"name":"Journal of pharmaceutical and biomedical analysis","volume":"265 ","pages":"Article 117054"},"PeriodicalIF":3.1,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144631618","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neuroinflammatory mechanism of Volatile oil from Acori graminei Rhizoma in tourette syndrome: GC-MS, network pharmacology and experimental validation","authors":"Kexin Sun ,&nbsp;Xing Wei ,&nbsp;Peng Feng ,&nbsp;Min Cui ,&nbsp;Shuang Huang ,&nbsp;Bing Jiang ,&nbsp;Qian Su ,&nbsp;Yanqin Ding ,&nbsp;Yongyan Tian ,&nbsp;Jiaxin Tan ,&nbsp;Yuezhen He ,&nbsp;Jing Shang ,&nbsp;Zhenggang Shi","doi":"10.1016/j.jpba.2025.117057","DOIUrl":"10.1016/j.jpba.2025.117057","url":null,"abstract":"<div><div>Tourette syndrome (TS) is a neurodevelopmental disorder characterized by tics that significantly impair childhood development. Volatile oil from <em>Acori graminei Rhizoma</em> (VOA), known for its anti-inflammatory and neuroprotective properties, holds therapeutic potential for TS, though its molecular mechanisms remain undefined. In this study, VOA was extracted via hydrodistillation (yield: 1.03 %), and the TS rat model was established to evaluate behavioral improvements through intragastric administration of varying VOA doses. The high-dose group (most effective in alleviating tics) was selected for subsequent mechanistic investigations. Utilizing GC-MS data from our group, network pharmacology and molecular docking analyses prioritized the cAMP/PKA/CREB signaling pathway as a potential target. Behavioral assessments confirmed that VOA significantly alleviated stereotyped and motor behaviors. In the striatum, VOA reduced pro-inflammatory cytokines, attenuated neuronal damage, and shifted microglial polarization from M1 to M2 phenotypes. From a mechanistic perspective, VOA upregulates key components in the cAMP/PKA/CREB signaling pathway and enhances BDNF levels, while suppressing the expression of NF-κB p65 and phosphorylation levels. These findings demonstrate that VOA mitigates tic behaviors by activating the cAMP/PKA/CREB signaling pathway, thereby curbing neuroinflammation, rectifying MG polarization, and preserving neuronal integrity. This study elucidates the critical link between TS pathogenesis and neuroinflammatory dysregulation, unveiling VOA’s molecular interplay with the cAMP/PKA/CREB signaling pathway and offering novel therapeutic insights for TS.</div></div>","PeriodicalId":16685,"journal":{"name":"Journal of pharmaceutical and biomedical analysis","volume":"265 ","pages":"Article 117057"},"PeriodicalIF":3.1,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144694589","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}