Journal of pharmaceutical and biomedical analysis最新文献

{"title":"Post-column denaturation-assisted hydrophobic interaction chromatography-mass spectrometry for rapid and in-depth characterization of positional isomers in cysteine-based antibody-drug conjugates.","authors":"Zhengqi Zhang, Anita P Liu, Hongxia Wang, Hillary A Schuessler","doi":"10.1016/j.jpba.2024.116635","DOIUrl":"https://doi.org/10.1016/j.jpba.2024.116635","url":null,"abstract":"<p><p>Antibody-drug conjugates (ADCs) represent a significant advancement in targeted cancer therapy, offering the potential to selectively deliver cytotoxic drugs to tumor cells while minimizing systemic toxicity. However, the structural complexity of ADCs, particularly those conjugated through cysteine residues, poses significant analytical challenges. Due to the hydrophobicity of ADCs, Hydrophobic interaction chromatography (HIC) is often the method of choice to analyze the drug-to-antibody ratio (DAR). However, it requires high-concentration salts, which are often incompatible with mass spectrometry (MS) analysis. By employing ammonium acetate as an MS-compatible salt and integrating a 4-way liquid junction cross configuration for simultaneous introduction of the makeup flow and splitting the flow right before coupling to a mass spectrometer, we achieve high-quality separation and sensitive mass spectrometric analysis. This innovative setup allows for simultaneous DAR measurement and positional isomer characterization by switching the makeup flow solvent from water to a denaturation solution. Our method offers a streamlined and effective approach to ADC characterization, facilitating the identification of positional isomers without the need for fractionation or multiple chromatographic steps. The versatility and robustness of this HIC-MS method are demonstrated through the analysis of two ADCs, highlighting its potential for broad application in ADC development and quality control.</p>","PeriodicalId":16685,"journal":{"name":"Journal of pharmaceutical and biomedical analysis","volume":"255 ","pages":"116635"},"PeriodicalIF":3.1,"publicationDate":"2024-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142864592","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":"Evidence for the metabolic activation of higenamine to quinone methide and ortho-quinone metabolites in vitro and in vivo using liquid chromatography tandem mass spectrometry.","authors":"Hui Wang, Lihua Xin, Pengyi Hou, Shiwei Sun, Jiang Zheng, Wei Wang","doi":"10.1016/j.jpba.2024.116634","DOIUrl":"https://doi.org/10.1016/j.jpba.2024.116634","url":null,"abstract":"<p><p>Higenamine (HG), a naturally occurring benzyltetrahydroisoquinoline alkaloid, has been revealed a variety of biological activities and is extensively utilized in dietary supplements. Currently, HG is under investigation in phase I clinical trials, however, the liver metabolism of HG has so far not been fully elucidated. The present study aimed to identify reactive metabolites of HG using ultrahigh-performance liquid chromatography-tandem mass spectrometry. Four glutathione (GSH) conjugates (M1-M4) and four cysteine conjugates (M5-M8) derived from reactive metabolites of HG were detected in GSH/cysteine-fortified mouse/human microsomal incubations. The cysteine conjugates were chemically synthesized for structural elucidation using manganese dioxide as the oxidizing agent. The reactive metabolites of HG were identified as quinone methide, hydroxyquinone methide, and ortho-quinone based on the fragmentation patterns of cysteine conjugates. Multiple CYP450 enzymes including CYP2D6, CYP3A4, and CYP2E1 were mediated in the formation of quinone methide, with the major role assigned to CYP2D6. While the oxidation of catechol to ortho-quinone metabolite and the subsequent isomerization into hydroxyquinone methide were independent of CYP450 isoforms. In addition, these electrophilic metabolites were found to react with biliary GSH and cysteine residues of hepatic protein in HG-treated mice. The in vitro and in vivo evidence of the metabolic activation of HG to quinone methide and ortho-quinone metabolites raised health concerns regarding the consumption of HG-containing supplements.</p>","PeriodicalId":16685,"journal":{"name":"Journal of pharmaceutical and biomedical analysis","volume":"255 ","pages":"116634"},"PeriodicalIF":3.1,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142829015","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":"Biotransformation analysis of daidzin in vitro based on fecal bacteria and probiotics.","authors":"Yuqing Wang, Zhe Li, Dongxue Wu, Zicheng Wang, Shaoping Wang, Quan Jiang, Xun Gong, Congmin Xia","doi":"10.1016/j.jpba.2024.116623","DOIUrl":"https://doi.org/10.1016/j.jpba.2024.116623","url":null,"abstract":"<p><p>Daidzin, as one of isoflavone glycosides, has been reported to have multiple activities with few absorbed into body. However, the metabolic behavior of daidzin by intestinal flora has not been researched, that this defect severely constrains its applications. In this study, daidzin and its metabolites were qualitatively and quantitatively analyzed by HPLC and ultra-high performance liquid chromatography coupled to high-resolution mass spectrometry (UHPLC-HRMS) in the fermentation system for daidzin and fecal bacteria. Meanwhile, the alterations of intestinal flora with daidzin were detected by 16S rRNA sequencing technology. Based on the results of intestinal flora, the daidzin and its metabolites transformed by the screened probiotics were quantified and qualified, which the results would corroborate the transformation of daidzin and fecal bacteria. Eventually, daidzin was decreased from 0.30158 mg/mL at 0 h to 0.01176 mg/mL at 48 h, daidzein, as the aglycone of daidzin, was increased from 0.02963 mg/mL at 0 h to 0.04682 mg/mL at 48 h, suggesting the presence of other metabolites. Next, 31 metabolites including the products of ketone removal, Retro-Diels-Alder (RDA) fragmentation, hydroxylation, methylation, C ring cracking and sulfation were identified. The results of 16S rRNA sequencing showed that the intestinal flora, especially Bifidobacterium, was dramatically altered after incubation with daidzin (p < 0.05). Hereby, the fermentation systems of five probiotics (Lactobacillus 3044, Bifidobacterium adolescentis 1.2190, Bifidobacterium longum 25033, Lactobacillus plantarum F1 and Lactobacillus plantarum B2) and daidzin were approved, and these results showed that most metabolites of daidzin were able to be identified with the identical transformation reactions. The study revealed the rationality of daidzin biotransformation at the new perspective, and constructs a new model for fecal metabolites of compounds. These results will also broaden the continued research on daidzin.</p>","PeriodicalId":16685,"journal":{"name":"Journal of pharmaceutical and biomedical analysis","volume":"255 ","pages":"116623"},"PeriodicalIF":3.1,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142882387","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":"Scaling analytical RP-HPLC to semi-preparative for fractionation and characterization of pegfilgrastim oxidized variants.","authors":"Haley Sutton, Teresa Youngberg, Christian Perez, Anke Hartung, Xuemei Han, Navin Rauniyar","doi":"10.1016/j.jpba.2024.116633","DOIUrl":"https://doi.org/10.1016/j.jpba.2024.116633","url":null,"abstract":"<p><p>Pegfilgrastim, a 40 kDa PEGylated form of recombinant human granulocyte colony-stimulating factor (rhG-CSF), is a biotherapeutic protein used to treat chemotherapy-induced neutropenia. To ensure the product is safe and effective, stringent monitoring of product-related impurities, particularly those arising from oxidative degradation, is necessary. This study focuses on the isolation and characterization of oxidized variants in pegfilgrastim using a multi-step approach that includes method transfer to semi-preparative High-Performance Liquid Chromatography (HPLC), mass spectrometry, and an in vitro cell-based potency assay (CBPA). The analytical reversed-phase (RP)-HPLC method was successfully scaled up and optimized for isolating oxidized variants in H₂O₂-treated pegfilgrastim. Mass spectrometry analysis identified the degree and specific sites of oxidation, with Met1 being the most susceptible. CBPA showed that oxidation at Met1 alone had minimal impact on functional activity, while oxidation at both Met127 and Met138 led to significant reductions in activity. The impact of oxidation at all four sites in pegfilgrastim could not be assessed due to significant degradation. These findings highlight the importance of robust analytical strategies in the characterization and control of pegfilgrastim impurities.</p>","PeriodicalId":16685,"journal":{"name":"Journal of pharmaceutical and biomedical analysis","volume":"255 ","pages":"116633"},"PeriodicalIF":3.1,"publicationDate":"2024-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142846859","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":"Analysis of solution-phase biomolecular interactions by liquid chromatography: General strategies and recent developments.","authors":"David S Hage, Sadia Sharmeen, Kyungah Suh, B K Sajeeb, Md Masudur Rahman, Jada Ayars","doi":"10.1016/j.jpba.2024.116632","DOIUrl":"https://doi.org/10.1016/j.jpba.2024.116632","url":null,"abstract":"<p><p>The analysis of biomolecular interactions is important in characterizing and understanding many fundamental processes that occur in the body and biological systems. A variety of methods are available for studying the extent and rate of binding of these interactions. Some of these techniques are homogeneous methods, with all interacting components being present in the solution-phase, while others are heterogeneous, such as involving both solution-phase and solid-phase components. LC and HPLC have often been used to study biomolecular processes. Although these chromatographic methods make use of both a liquid phase (i.e., the mobile phase and applied samples) and a solid phase (the stationary phase and support), they can be used to study solution-phase interactions. This review examines several strategies that have been developed and employed to use LC and HPLC for this purpose. These strategies include the Hummel-Dreyer method, solution-phase frontal analysis, and the use of physical entrapment for a soluble component of a biomolecular interaction. Other strategies that are discussed are those in which the stationary phase of the column is used as a secondary component or capture agent when studying a solution-phase interaction, as occurs in normal-role affinity chromatography and ultrafast affinity extraction. The general principles for each of these strategies will be considered, along with their advantages, potential limitations, and applications.</p>","PeriodicalId":16685,"journal":{"name":"Journal of pharmaceutical and biomedical analysis","volume":"255 ","pages":"116632"},"PeriodicalIF":3.1,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142824272","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":"Comparisons of the bioavailability of icariin, icariside II, and epimedin C in rats after oral administration of total flavonoids of Epimedium brevicornu Maxim. and its three formulations.","authors":"Zhiyuan Ding, Xiuping Chen, Dongyun Tang, Taiwei Ye, Juan Yang, Yilin Yu, Yan Xie","doi":"10.1016/j.jpba.2024.116631","DOIUrl":"https://doi.org/10.1016/j.jpba.2024.116631","url":null,"abstract":"<p><p>The low bioavailability of insoluble flavonoids in the total flavonoids of Epimedium brevicornu Maxim. (TFE) severely hindered its clinical efficacy exertion. This research attempted to evaluate the promoting effects of pharmaceutical strategies, including nanosuspensions (NS), cyclodextrin inclusion complexes (CD), and solid dispersions (SD), on the oral absorption of active components in TFE. A rapid ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method was established to quantify ten pentenyl flavonoids of TFE in rat plasma. Good linearity was presented within the expected ranges (0.1 ∼ 10 ng/mL) in the calibration curves for ten analytes with an acceptable intra- and inter-day precision and accuracy of < 11.34 % and ± 11.91 %, respectively. By employing this selective UPLC-MS/MS method, the full-scale concentration-time curve for icariin (ICA), icariin II (ICA II), and epimedin C (EPI C) were drawn after oral administration of the crude TFE and its formulations. The results showed that the relative bioavailability (F_rel) of ICA and ICA II in the NS and CD formulations were 228-295 % when the crude TFE was as a reference, whereas the F_rel of ICA, ICA II, and EPI C in SD formulation were 416 %, 234 %, and 112 %, respectively. The findings suggest that SD technology holds significant promise for enhancing the oral bioavailability of various poorly soluble ingredients in herbal extracts, such as TFE, and for augmenting their therapeutic capabilities in clinical practice.</p>","PeriodicalId":16685,"journal":{"name":"Journal of pharmaceutical and biomedical analysis","volume":"255 ","pages":"116631"},"PeriodicalIF":3.1,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142822200","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":"Dynamic profiling of intra- and extra-cellular L/D-amino acids metabolism in colorectal cell and intestinal epithelial cell.","authors":"Wenchan Deng, Rongrong Huang, Yuanjiang Pan, Cuirong Sun","doi":"10.1016/j.jpba.2024.116622","DOIUrl":"https://doi.org/10.1016/j.jpba.2024.116622","url":null,"abstract":"<p><p>The metabolism process of amino acids is closely related to the growth of normal and cancer cells. It is still not clear how L/D-configuration amino acids participate in the metabolism of colorectal cell. Herein, intra- and extra-cellular metabolic distribution of L/D-amino acids in colorectal cell (HCT116) and human normal intestinal epithelial cell (NCM460) were profiled utilizing HPLC-MS/MS coupled with a chiral probe. The results displayed the differential metabolic portrayal for the two cell lines. Compared with NCM460 cell, 13 kinds of significant differential amino acids were founded in a lower concentration within HCT116 cell, and L-Gln was even not detected for intra-cell; as for extra-cell culture medium, the HCT116 cell consumed more L-Gln, D-Phe and D-Leu, while L-Met was low ingested in HCT116 cell. L-Ala and Gly were excretion in both two cell lines, excepted L-Cit which was uptake in HCT116 and excretion in NCM460 cell. Furthermore, the dynamic changes of chiral amino acids displayed that phenylalanine, tyrosine and tryptophan biosynthesis and arginine biosynthesis is the major pathway for intra-cellular metabolites and extra-cellular metabolites, respectively. Moreover, with additional D-amino acids in culture medium, the results exhibited that high concentration of D-amino acids have no significant effect on the proliferation of NCM460 cell, but could influence the profiling of amino acids metabolites, and further affect the proliferation of HCT116 cell. This present work enhances the understanding of these differential amino acids metabolic network and depicts a dynamic process of metabolic dysregulation of HCT116 and NCM460 cell.</p>","PeriodicalId":16685,"journal":{"name":"Journal of pharmaceutical and biomedical analysis","volume":"255 ","pages":"116622"},"PeriodicalIF":3.1,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142807052","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":"Metabolite profiling of Shenhua compound in rats and pharmacokinetics study of four bioactive compounds with liquid chromatography combined with electrospray ionization tandem mass spectrometry.","authors":"Ze-Xuan Chen, Ling Li, Jie Tang, Meng-Ge Shi, Xue-Yee Lim, Pei-Rong Song, Lu Zou, Han Han, Yun Gu, Tong Zhang","doi":"10.1016/j.jpba.2024.116626","DOIUrl":"https://doi.org/10.1016/j.jpba.2024.116626","url":null,"abstract":"<p><p>Shenhua compound, composed of ginseng, hawthorn and sophora flower, has been shown to improve hyperlipidemia. However, the main ingredients, their metabolic pathways in vivo, and pharmacokinetic characteristics. In this study, ultra-high-performance liquid chromatography coupled with electrospray ionization quadruple time-of-flight mass spectrometry (UHPLC-Q-TOF) was used to qualitatively analyze the main ingredients in ethanol extract of Shenhua compound and to investigate the metabolites in serum, bile, feces, and urine of rats following oral administration. The pharmacokinetics of ginsenoside Rg₁, ginsenoside Re, ginsenoside Ro and rutin in rats were analyzed using triple-quadrupole liquid chromatography combined with electrospray ionization mass spectrometry (QQQ-LC/MS). The results indicated that 48 compounds were present in Shenhua compound, including saponins, flavonoids and organic acids. Metabolites were comprehensively analyzed after oral administration of Shenhua compound, and 24 prototype ingredients and 92 metabolite ingredients were identified or characterized. By analyzing the pharmacokinetic parameters of ginsenoside Rg₁, ginsenoside Re, ginsenoside Ro and rutin from 0 to 72 h after oral administration of various dose of Shenhua compound, it was observed that the concentration of ginsenosides in blood remained below 2 ng∙mL¹, but the metabolic excretion time was prolonged. Meanwhile, the blood concentration of rutin was significantly higher than ginsenosides and showed a double absorption peak. In conclusion, this study provides valuable insights into compound ingredients metabolism regularities in vivo and pharmacokinetics after oral administration of Shenhua compound.</p>","PeriodicalId":16685,"journal":{"name":"Journal of pharmaceutical and biomedical analysis","volume":"255 ","pages":"116626"},"PeriodicalIF":3.1,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142822284","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":"Quantification of serum daratumumab in multiple myeloma patients by LC-MS/MS, comparison with ELISA.","authors":"Weiqiang Li, Zhuoran Tian, Xiong Yu, Hongyu Xu, Fang Huang, Jinghua Yu, Xingxing Diao","doi":"10.1016/j.jpba.2024.116627","DOIUrl":"https://doi.org/10.1016/j.jpba.2024.116627","url":null,"abstract":"<p><p>Daratumumab is a fully human immunoglobulin G1 monoclonal antibody employed for treating relapsed/refractory multiple myeloma and light-chain amyloidosis. Quantifying monoclonal antibodies in serum presents challenges due to interference from biological matrices. This research aimed to develop and verify an liquid chromatography tandem-mass spectrometry (LC-MS/MS) approach for quantifying serum daratumumab, employing immunoglobulin G purification without alkylation, and to assess its applicability in patients with multiple myeloma receiving intravenous daratumumab. The chromatographic peaks of the daratumumab-derived peptides and internal standard were well-delineated from the serum digests, with an overall run time of 14 min. The calibration curves for serum daratumumab were linear across over 1-1000 μg/mL. The inter- and intra-day accuracy varied between 92.4 % and 108.4 %, with a coefficient-of-variation below 10 %. In patients receiving intravenous daratumumab, serum concentrations ranged from 181.8 to 975.3 µg/mL. Bland-Altman analysis revealed no significant bias, and Passing-Bablok regression demonstrated a good agreement between the LC-MS/MS method and enzyme-linked immunosorbent assay.</p>","PeriodicalId":16685,"journal":{"name":"Journal of pharmaceutical and biomedical analysis","volume":"255 ","pages":"116627"},"PeriodicalIF":3.1,"publicationDate":"2024-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142822285","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, mass cytometry and multi-omics analysis the effect of Jingfang granule on intestinal immune disorder in mice with cold-dampness syndrome.","authors":"Shirong Li, Mingfei Liu, Lihong Pan, Qun Feng, Xiaoyan Lu, Jingchun Yao, Xuefeng Xiao","doi":"10.1016/j.jpba.2024.116624","DOIUrl":"https://doi.org/10.1016/j.jpba.2024.116624","url":null,"abstract":"<p><p>The pathogenesis of cold-dampness syndrome (CDS) is closely related to intestinal inflammation and immune disorders induced by cold-dampness pathogen. CDS is the root cause of a variety of chronic inflammatory and immune diseases. Jingfang granule (JF) was widely used to treat a variety of diseases closely related to CDS. JF is well known for its clinical effect of dispelling cold and eliminating dampness, but the pharmacological effect and mechanism of JF on the improvement of CDS are still unclear. This study aimed to explore the efficacy and mechanism of JF in improving CDS from the perspective of intestinal immunity. In this study, mass spectrometry (CyTOF), metabolomics, network pharmacology, proteomics and molecular biology experiments were performed to investigate the therapeutic effects and underlying mechanisms of JF on intestinal inflammation and immune disorders in CDS mice. These results showed that JF could improve the clinical symptoms and increase the thymus index of CDS mice. Most strikingly, JF ameliorated intestinal inflammation and immune disorders in CDS mice, as indicated by increased frequency of TH1, CD8 + Tem, CD8 + TEFF, gdT and iNK cells and decreased frequency of Naive B cells, M1-macrophages, DCs and eosinophils. Metabolomics results showed that JF reversed the content of docosahexaenoic acid, arachidonic acid, linoleic acid, inosine and hypoxanthine in CDS mice. Correlation analysis showed that these metabolites were strongly correlated with a variety of intestinal immune cells, indicating that there was a certain regulatory effect between them. Then, 271 JF targets, 316 metabolite targets and 18374 disease targets were integrated to obtain 75 common targets and 138 pathways (such as PI3K/AKT and MAPK pathway, etc). Furthermore, molecular docking, proteomics and western blotting demonstrated that PI3K/AKT signaling pathway might be the key molecular mechanism by which JF regulated intestinal immune disorders in CDS mice. These results suggested that JF may act on the PI3K/AKT pathways to further regulate the levels of metabolites to exert intestinal immunomodulatory effects. In summary, we confirmed the beneficial effects of JF on intestinal immune disorders in CDS mice.</p>","PeriodicalId":16685,"journal":{"name":"Journal of pharmaceutical and biomedical analysis","volume":"255 ","pages":"116624"},"PeriodicalIF":3.1,"publicationDate":"2024-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142807071","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}