Journal of pharmaceutical and biomedical analysis最新文献

{"title":"Separation of tolperisone and its degradation products by a dual cyclodextrin capillary electrophoresis system to study their potential role in allergic events","authors":"Péter P. Lakatos ,&nbsp;Zsuzsanna Ignáth ,&nbsp;Orsolya Csernák ,&nbsp;Imre Boldizsár ,&nbsp;Éva Szökő ,&nbsp;Tamás Tábi","doi":"10.1016/j.jpba.2024.116532","DOIUrl":"10.1016/j.jpba.2024.116532","url":null,"abstract":"<div><div>Tolperisone is a centrally acting muscle relaxant that has been used for the treatment of post-stroke spasticity and low back pain. Recently, the safety of tolperisone pharmaceutical products has been reassessed due to growing concerns over allergic adverse events. Reactive degradants of tolperisone may be responsible for these hypersensitivity reactions. By forming adducts with proteins, they may act as haptens that could evoke allergic reactions. The objective of this study was to examine the presence of these degradants in tolperisone pharmaceutical products and to assess their reactivity to elucidate their possible role in the pro-allergic effect of tolperisone. For this purpose, capillary electrophoresis UV detection (CE-UV) method was developed and validated for the quantification of degradants. A dual cyclodextrin system was applied to achieve the appropriate migration order enabling the analysis of 2-methyl-1-(4-methylphenyl)prop-2-en-1-one (MMP) and 1-(4-methylphenyl)propan-1-one (MMPO) in the presence of high concentrations of tolperisone. MMP was identified as the main degradant in forced degradation tests of the active pharmaceutical ingredient. Differences in MMP content of tolperisone products by different manufacturers have also been found, highlighting the role of formulation in their stability. High reactivity of MMP was demonstrated as rapid and almost complete adduct formation with cysteine was found. This degradant thus might be responsible for the allergic adverse effects of tolperisone even when it is present in trace amounts in tablets by readily reacting with proteins <em>in vivo</em>.</div></div>","PeriodicalId":16685,"journal":{"name":"Journal of pharmaceutical and biomedical analysis","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142468220","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Characterization of disulfide bridges containing cyclic peptide Linaclotide and its degradation products by using LC-HRMS/MS","authors":"Sachin Chaturvedi,&nbsp;Nikhil Titkare,&nbsp;Nitish Sharma,&nbsp;Ravi P. Shah","doi":"10.1016/j.jpba.2024.116533","DOIUrl":"10.1016/j.jpba.2024.116533","url":null,"abstract":"<div><div>Linaclotide (LINA) is a first-in-class guanylate cyclase agonist used for treating irritable bowel syndrome with constipation (IBS-C) and chronic idiopathic constipation. Stress degradation studies were performed to examine LINA's intrinsic stability, adhering to International Council for Harmonisation of Technical ICH) guidelines Q1A (R2). The current study endeavours to elucidate the stability behavior of LINA by exposing various stress conditions. A simple LC method was developed for effective separation of all LINA degradation products using a Waters Symmetry C18 column (150 ×4.6 mm, 3.5 µm) as the stationary phase. The generated degradation products were identified and characterized by using high-resolution mass spectrometry (LC-HRMS), MS/MS studies. The mechanistic fragmentation pathway for the seven degradation products was established and the chemical structure for the identified degradation products was elucidated. LINA was susceptible to degrade under acidic, basic, neutral, photolytic, and oxidative conditions. A total of three Pseudo DPs, DP-1, DP-2, and DP-3, were formed under acidic conditions while using methanol as the co-solvent. Additionally, degradation products (DPs) were identified: DP-4 formed under basic stress condition and DP-5 under neutral, thermal, and photolytic conditions. Furthermore, DP-6 and DP-7 were formed under oxidative stress condition. This study established the mechanistic fragmentation pathways and elucidated the chemical structures of the degradation products, offering valuable insights for generics and novel formulation drug development.</div></div>","PeriodicalId":16685,"journal":{"name":"Journal of pharmaceutical and biomedical analysis","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142468217","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":"Plasma-based proteomic and metabolomic characterization of lung and lymph node metastases in cervical cancer patients","authors":"Yue Feng ,&nbsp;Zijian Sun ,&nbsp;Huan Zhang ,&nbsp;Zhao Wang ,&nbsp;Lichao Wang ,&nbsp;Hui Ye ,&nbsp;Xiaojing Zhang ,&nbsp;Zhuomin Yin ,&nbsp;Juan Ni ,&nbsp;Jingkui Tian ,&nbsp;Hanmei Lou ,&nbsp;Xiaojuan Lv ,&nbsp;Wei Zhu","doi":"10.1016/j.jpba.2024.116521","DOIUrl":"10.1016/j.jpba.2024.116521","url":null,"abstract":"<div><div>Metastasis is the leading cause of mortality in cervical cancer (CC), with a particular prevalence of lymph node and lung metastases. Patients with CC who have developed distant metastases typically face a poor prognosis, and there is a scarcity of non-invasive strategies for predicting CC metastasis. In this study, we utilized label-free proteomics and untargeted metabolomics to analyze plasma samples from 25 non-metastatic, 14 with lung metastasis, and 15 with lymph node metastasis CC patients. Pathway enrichment analysis revealed a shared inflammatory process between the two metastatic groups, while the central carbon metabolism in cancer showed distinct features in the lung metastasis cohort. Additionally, cholesterol metabolism, hypoxia-inducible factor 1, and ferroptosis signaling pathways were specifically altered in the lymph node metastasis group. Utilizing the receiver operating characteristic curve analysis and Random Forest algorithm, we identified two distinct biomarker panels for the prediction of lung metastasis and lymph node metastasis, respectively. The lung metastasis panel includes properdin, neural cell adhesion molecule 1, and keratin 6 A, whereas the lymph node metastasis panel consists of quiescin sulfhydryl oxidase 1, paraoxonase 1, and keratin 6 A. Each panel exhibited significant diagnostic potential, with high area under the curve (AUC) values for lung metastasis (training set: 0.989, testing set: 0.789) and lymph node metastasis (training set: 0.973, testing set: 0.900). This study conducted an integrated proteomic and metabolomic analysis to clarify the factors contributing to lung and lymph node metastases in CC and has successfully established two biomarker panels for their prediction.</div></div>","PeriodicalId":16685,"journal":{"name":"Journal of pharmaceutical and biomedical analysis","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142502459","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":"Assay for the quantification of abemaciclib, its metabolites, and olaparib in human plasma by liquid chromatography-tandem mass spectrometry","authors":"Kasey L. Hill ,&nbsp;Nicole L. Abbott ,&nbsp;Joo Young Na ,&nbsp;Michelle Rudek ,&nbsp;Kathleen Moore ,&nbsp;Eudocia Q. Lee ,&nbsp;Mitch A. Phelps","doi":"10.1016/j.jpba.2024.116531","DOIUrl":"10.1016/j.jpba.2024.116531","url":null,"abstract":"<div><div>An isotope-dilution bioanalytical assay for abemaciclib and its metabolites in combination with olaparib was developed and validated in human plasma K2 EDTA. For the quantitative assay, human plasma samples (or human plasma QC samples) were spiked with internal standard solution before a simple protein precipitation with methanol. The extract was injected onto a liquid chromatography-tandem mass spectrometry (LC-MS/MS) instrument where it was chromatographically separated by a polar end-capped reversed phase column and guard using gradient elution with water and methanol both modified with 0.2 % formic acid (v/v) as the mobile phases. The analytes and internal standards were measured by heated electrospray ionization (HESI) in positive polarity using selected reaction monitoring (SRM) on a triple quadrupole mass spectrometer. The assay was validated for linear ranges as follows: 0.4 – 1000 nM abemaciclib, 0.35 – 1000 nM M2 and M18, 0.5 – 1000 nM M20, and 0.75 – 1000 nM olaparib. The inter-day or between day precision for the quality controls (n = 18) was &lt; 13 % and the accuracy was ± 12 %, for all analytes, including the lower limit of quantification (LLOQ). The intra-day or within day precision for the quality controls (n = 6) was ≤ 11 % and the accuracy was ± 12 % for low, mid, and high and &lt; 19 % at LLOQ. The recovery in human plasma was determined to be between 92 % and 102 % for all analytes spanning the linear range. The validated, bioanalytical quantitative assay was designed to measure abemaciclib, its metabolites, and olaparib for pharmacokinetic evaluation of patients in clinical trials for breast, brain, and ovarian cancers.</div></div>","PeriodicalId":16685,"journal":{"name":"Journal of pharmaceutical and biomedical analysis","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142502446","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":"LC-HRMS-based global metabolomics profiling unravels the distinct metabolic signature of lapatinib-resistant and trastuzumab-resistant HER2+ breast cancer cells","authors":"Adam Hermawan ,&nbsp;Anjar Windarsih ,&nbsp;Dyaningtyas Dewi Pamungkas Putri ,&nbsp;Nurul Fatimah","doi":"10.1016/j.jpba.2024.116528","DOIUrl":"10.1016/j.jpba.2024.116528","url":null,"abstract":"<div><div>The effectiveness of lapatinib (LAP) and trastuzumab (TRZ), the first-line therapies for HER2⁺ breast cancer, has been limited owing to the development of acquired resistance in patients with HER2⁺. This study aimed to investigate the alterations in metabolic signatures in LAP-resistant HCC1954 and TRZ-resistant HCC1954 and pathways in human HER2⁺ breast cancer cells using liquid chromatography–high-resolution mass spectrometry (LC-HRMS) and enrichment analysis. The HCC1954 parental cells were sequentially treated 13 rounds with LAP or TRZ to develop resistant cells and then tested for their cytotoxicity using the MTT assay. Metabolites were prepared from HCC1954 parental (MBXWT), HCC1954-LAP (MBXLAP), and HCC1954-TRZ (MBXTRZ) cells prior to LC-HRMS, chemometric, enrichment, and joint pathway analyses. LAP- and TRZ-resistant cells were successfully developed from HCC1954, and 29 and 17 differentially expressed metabolites (DEMs) were identified between MBXWT-MBXLAP and MBXWT-MBXTRZ, respectively. The analysis of DEMs between MBXWT and MBXLAP revealed significant enrichment in D-amino acid metabolism, while MBXWT and MBXTRZ identified valine, leucine, isoleucine biosynthesis, ascorbate, and aldarate metabolism. Joint pathway enrichment analysis of LAP-resistant DEMs and differentially expressed genes (DEGs) showed enrichment in glutathione metabolism, while that of TRZ-resistance and DEGs showed enrichment in carbohydrate metabolism, namely pentose and glucuronate interconversions, starch and sucrose metabolism, and galactose metabolism. The findings from this study indicate considerable metabolic changes in LAP- and TRZ-resistant HCC1954 cells, which are crucial for understanding the resistance mechanisms and developing strategies to overcome these problems.</div></div>","PeriodicalId":16685,"journal":{"name":"Journal of pharmaceutical and biomedical analysis","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142502458","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":"Method validation and determination of pesticides in Mikania glomerta Spreng tincture by direct injection and UPLC-MS/MS analysis","authors":"Thais Morais de Brito ,&nbsp;Angélica Castanheira de Oliveira ,&nbsp;Fabio Coelho Amendoeira ,&nbsp;Lucia Helena Pinto Bastos ,&nbsp;Maria Helena Wohlers Morelli Cardoso ,&nbsp;Leandro Machado Rocha ,&nbsp;Armi Wanderley da Nóbrega ,&nbsp;Fausto Klabund Ferraris","doi":"10.1016/j.jpba.2024.116527","DOIUrl":"10.1016/j.jpba.2024.116527","url":null,"abstract":"<div><div>Over the past two decades, concerns have arisen about the efficacy and safety of medicinal plants, highlighting good agricultural practices and quality control. This study aimed to validate a multi-residue analysis method for detecting 268 pesticides in Mikania glomerata tincture, using direct injection and UPLC-MS/MS, per SANTE guidelines. The validation of the method involved evaluating the linearity of analytical curves in terms of the determination coefficient r2 and residuals (%), as well as the limits of quantification (LOQ), matrix effects, precision (expressed as the coefficient of variation, CV), and accuracy (determined as the recovery percentage). The parameters and acceptance criteria were assessed based on SANTE guidelines. The method was then applied to analyse commercial samples of <em>M. glomerata</em> tincture, and traces of carbendazim and dimethomorph were detected. This study underscores the need for regulatory measures to enhance agricultural practices, thereby ensuring the safety and efficacy of medicinal plants.</div></div>","PeriodicalId":16685,"journal":{"name":"Journal of pharmaceutical and biomedical analysis","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142468218","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":"Raman spectroscopy for monitoring free sulfhydryl formation during monoclonal antibody manufacturing","authors":"Zhenshu Wang ,&nbsp;Andrew Hsieh ,&nbsp;Patricia Rose ,&nbsp;George Zhou ,&nbsp;Sonja Battle ,&nbsp;Kelly Raymond ,&nbsp;Monica Haley ,&nbsp;Aaron Cote ,&nbsp;Sandra Bennun ,&nbsp;Sanjeev Ahuja","doi":"10.1016/j.jpba.2024.116530","DOIUrl":"10.1016/j.jpba.2024.116530","url":null,"abstract":"<div><div>During production, harvested cell culture fluid (HCCF) can degrade due to reductases breaking interchain disulfide bonds, forming low molecular weight (LMW) impurities that contain free sulfhydryl and high molecular weight (HMW) impurities through disulfide shuffling. Thus, detecting and quantifying the free sulfhydryl increase in HCCF is critical. Herein, Raman spectroscopy is implemented as a process analytical technology, and multivariate data analysis is applied to characterize and quantify sulfhydryl formation in HCCF with disulfide-containing indicator molecules. Raman spectra qualitatively probe the presence or absence of disulfide bond breakage in antibodies, consistent with offline non-reduced capillary electrophoresis sodium dodecyl sulfate results. Between two antibodies studied, mAb A was identified for a higher risk of antibody reduction where sulfhydryl formation was observed within 16 h, while mAb B did not show similar concerns even after 1 week. The offline measurement of redox potential is below –100 mV in HCCF for mAb A, while the stable mAb B HCCF shows redox potentials above +20 mV. A multivariate partial least squares (PLS) model for quantification is developed using an offline free sulfhydryl assay, applying Raman spectra to predict free sulfhydryl concentration with high accuracy (R² &gt; 0.98) and expected mean error of 0.677 mM from the offline Ellman’s Assay. This work confirms the use of Raman PAT to monitor real-time disulfide reduction, enabling improvements to process understanding and product quality.</div></div>","PeriodicalId":16685,"journal":{"name":"Journal of pharmaceutical and biomedical analysis","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142502444","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":"Characterization of adeno-associated virus capsid proteins using denaturing size-exclusion chromatography coupled with mass spectrometry","authors":"Timothy N. Tiambeng,&nbsp;Yuetian Yan,&nbsp;Shailin K. Patel,&nbsp;Victoria C. Cotham,&nbsp;Shunhai Wang,&nbsp;Ning Li","doi":"10.1016/j.jpba.2024.116524","DOIUrl":"10.1016/j.jpba.2024.116524","url":null,"abstract":"<div><div>Recombinant adeno-associated viruses (AAVs) are a highly effective platform for gene delivery for the treatment of many human diseases. Characterization of AAV viral protein attributes (VP), such as serotype identity, VP stoichiometry, and VP post-translational modifications, is essential to ensure product and process consistency. While size-exclusion chromatography (SEC) coupled with mass spectrometry (MS) is commonly used in the biopharmaceutical industry for analyzing protein therapeutics, its application to intact AAV VP components has not gained traction, presumably due to difficulties in achieving adequate resolution of VP(1−3) monomers. Herein, we describe the development of a denaturing SEC method and optimization of SEC parameters, including stationary phase pore size, column temperature, and mobile phase composition, to achieve effective chromatographic separation of VP(1−3). We demonstrate that an optimized dSEC-MS method featuring MS-compatible formic acid, can effectively separate VP(1−3) across AAV1, 2, 5, 6, 8, and 9 serotypes using a single column and mobile phase condition. A case study was included to showcase successful application of the dSEC-MS method in analyzing changes across different AAV production processes, yielding similar conclusions to an orthogonal approach, such as hydrophilic interaction chromatography (HILIC)- MS. Additionally, dSEC integrated with fluorescence (FLR) and ultraviolet (UV) detection can be used to semi-quantitatively identify both AAV DNA and VP components from empty and full AAV samples. Overall, this robust and MS-friendly methodological advancement could greatly streamline the development and analytical quality control processes for AAV-based gene therapies, providing a highly sensitive method for intact VP characterization.</div></div>","PeriodicalId":16685,"journal":{"name":"Journal of pharmaceutical and biomedical analysis","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142502447","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Low polarity fraction of Radix Bupleuri alleviates chronic unpredictable mild stress-induced depression in rats through FXR modulating bile acid homeostasis in liver, gut, and brain","authors":"Weiyu Wang ,&nbsp;Xue Bai ,&nbsp;Jing Li ,&nbsp;Shuheng Wang ,&nbsp;Fang Zhao ,&nbsp;Xuemei Qin ,&nbsp;Xiaoxia Gao","doi":"10.1016/j.jpba.2024.116523","DOIUrl":"10.1016/j.jpba.2024.116523","url":null,"abstract":"<div><div>Radix Bupleuri (BR, <em>Bupleurum chinense</em> DC.) is a well-known traditional Chinese medicine (TCM) known for its effects on soothing the liver and alleviating depression, and is widely used in clinical settings to manage depressive symptoms. A dosage of 12.5 g crude drug/kg/d of the low-polarity fraction of Radix Bupleuri (LBR) demonstrated effectiveness in treating depression in our previous study. However, the mechanism through which BR ameliorates depression remains unclear. This study aimed to explore the polar fractions of BR and their mechanisms of action in the treatment of depression. Chronic unpredictable mild stress (CUMS) rats were continuously administered BR by oral gavage for 4 weeks. Behavioral and biochemical indicators were evaluated to assess the antidepressant effects of LBR, and transcriptomics was used to explore the relevant pathways. In addition, pseudo-targeted bile acid (BA) metabonomics was used to quantify the BA profiles. Molecular biology techniques have been used to investigate the underlying mechanisms. LBR serves as a more effective active fraction with antidepressant activity. Intervention with LBR, which is characterized by a clearly defined chemical composition, significantly ameliorated depression-like behavior and biochemical indicators in rats subjected to CUMS. Notably, marked improvements were observed in the levels of total bile acids (TBAs) in the blood, liver, and ileum. Mechanistically, liver transcriptome analysis suggested that bile secretion may be a crucial pathway for alleviating depression after LBR treatment. Ultra-high performance liquid chromatography-mass spectrometry (UPLC-MS) BA metabonomics indicated that TCA, β-MCA, γ-MCA, Tβ-MCA, and UDCA in the liver, Tβ-MCA, TCA, βMCA, GHDCA, and GLCA in the ileum, and β-MCA, CA, and DCA in the hippocampus were the potential therapeutic targets. In addition, molecular biology experiments showed that LBR exerts antidepressant effects by regulating the FXR/SHP/CYP7A1 pathway in the liver, the FXR/FGF15/ASBT pathway in the ileum, and the FXR/CREB/BDNF pathway in the hippocampus. In conclusion, LBR attenuated depression by moderating BA homeostasis through FXR and related genes within the liver-gut-brain axis.</div></div>","PeriodicalId":16685,"journal":{"name":"Journal of pharmaceutical and biomedical analysis","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142531557","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":"Proteomic and network pharmacology analyses reveal S100A8 as the anti-inflammatory target of Yunpi Jiedu Tongluo Qushi Granule in the treatment of rheumatoid arthritis","authors":"Chenyi Yu ,&nbsp;Honglv Jiang ,&nbsp;Meijiao Wang ,&nbsp;Yi Zhang ,&nbsp;Zhijun Xie ,&nbsp;Yajun Wang ,&nbsp;Guoqiang Xu","doi":"10.1016/j.jpba.2024.116522","DOIUrl":"10.1016/j.jpba.2024.116522","url":null,"abstract":"<div><div>Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease characterized by synovial inflammation. RA has a global prevalence between 0.5 % and 1 % although its pathogenesis is not completely understood. Chinese herbal medicine such as Yunpi Jiedu Tongluo Qushi Granule (YJTQG) is one of the treatments for RA. However, the underlying mechanism of action is unclear. Here, analysis of clinical samples reveals that YJTQG can reduce the inflammatory factors and alleviate the symptoms of RA patients. Quantitative proteomic analysis of serum proteomes of RA patients identifies the potential therapeutic targets of YJTQG. We use biochemical experiments to validate several differentially expressed proteins, discover S100A8 as a possible therapeutic target of YJTQG, and analyze the correlation between S100A8 and several known RA biomarkers. Network pharmacology analysis discloses COX1/2 and NOS2 as potential targets of key compounds in YJTQG and protein-protein interaction network analysis reveals TNFα, IL-6, and STAT3 as possible core targets of YJTQG. Bioinformatic and patient sample analyses indicate that YJTQG may reduce S100A8 expression by suppressing its transcription. Mechanistically, we find that kaempferol and quercetin in YJTQG may reduce the expression of S100A8 by inhibiting the phosphorylation, nuclear translocation, and transcriptional activity of p65 in the lipopolysaccharide-stimulated RAW264.7 cells. Therefore, our work demonstrates that S100A8 is a potential therapeutic target of YJTQG for RA, which may provide a new direction for developing new treatments for RA patients.</div></div>","PeriodicalId":16685,"journal":{"name":"Journal of pharmaceutical and biomedical analysis","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142502443","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}