Pub Date : 2024-11-08DOI: 10.1016/j.jchromb.2024.124352
Ming Zhang, Yang Jin, Tiantai Wu, Qing Zhao, Herong Li, Huan Zhang, Yuan Lu, Shuaishuai Chen, Ting Liu, Zipeng Gong, Daoping Wang, Wen Liu
Ulcerative colitis (UC) is a common disease of the digestive system that is challenging to treat. Gegen Qinlian Decoction (GQD), which is an ancient classic formula in Chinese medicine, is effective at alleviating the symptoms of UC, but comprehensive research on its mechanism of action has not been performed. Here, we explored the material basis and potential molecular mechanism underlying GQD-mediated protection against UC by integrated metabolomics and network pharmacology. First, differentially expressed metabolites were screened and identified via a metabolomics approach, and the metabolic pathway was analyzed via MetaboAnalyst. Second, a protein-protein interaction (PPI) network was constructed to identify hub genes that encode metabolic enzymes. Third, the differentially expressed metabolites were used to construct a compound-reaction-enzyme-gene network. Finally, the metabolites were compared with relevant active components for molecular docking, molecular dynamics (MD) simulation, and verification experiment. GQD intervention alleviated UC in mice and significantly inhibited metabolic dysfunction in mice with UC; specifically, GQD reversed the abnormal changes in metabolites in the colon and serum, and regulated the arachidonic acid metabolism, tryptophan metabolism, glycerophospholipid metabolism, and purine metabolism pathways. Further literature review and molecular docking analysis with targeted MD simulation and Poisson-Boltzmann surface area (MM-PBSA) analysis were performed, revealing that GQD may inhibit the disruption of arachidonic acid metabolism and tryptophan metabolism by suppressing PTGS2 and CYP450 protein expression; these results were verified by qRT-PCR, WB, and surface plasmon resonance (SPR) assays. Our experiments indicated that GQD alleviated UC in mice by systematically regulating arachidonic acid metabolism and tryptophan metabolism, supporting further research and the development of GQD as a novel drug for ameliorating UC.
{"title":"Metabolomics combined with network pharmacology revealed a paradigm for determining the mechanism underlying the metabolic action of Gegen Qinlian Decoction amelioration of ulcerative colitis in mice.","authors":"Ming Zhang, Yang Jin, Tiantai Wu, Qing Zhao, Herong Li, Huan Zhang, Yuan Lu, Shuaishuai Chen, Ting Liu, Zipeng Gong, Daoping Wang, Wen Liu","doi":"10.1016/j.jchromb.2024.124352","DOIUrl":"https://doi.org/10.1016/j.jchromb.2024.124352","url":null,"abstract":"<p><p>Ulcerative colitis (UC) is a common disease of the digestive system that is challenging to treat. Gegen Qinlian Decoction (GQD), which is an ancient classic formula in Chinese medicine, is effective at alleviating the symptoms of UC, but comprehensive research on its mechanism of action has not been performed. Here, we explored the material basis and potential molecular mechanism underlying GQD-mediated protection against UC by integrated metabolomics and network pharmacology. First, differentially expressed metabolites were screened and identified via a metabolomics approach, and the metabolic pathway was analyzed via MetaboAnalyst. Second, a protein-protein interaction (PPI) network was constructed to identify hub genes that encode metabolic enzymes. Third, the differentially expressed metabolites were used to construct a compound-reaction-enzyme-gene network. Finally, the metabolites were compared with relevant active components for molecular docking, molecular dynamics (MD) simulation, and verification experiment. GQD intervention alleviated UC in mice and significantly inhibited metabolic dysfunction in mice with UC; specifically, GQD reversed the abnormal changes in metabolites in the colon and serum, and regulated the arachidonic acid metabolism, tryptophan metabolism, glycerophospholipid metabolism, and purine metabolism pathways. Further literature review and molecular docking analysis with targeted MD simulation and Poisson-Boltzmann surface area (MM-PBSA) analysis were performed, revealing that GQD may inhibit the disruption of arachidonic acid metabolism and tryptophan metabolism by suppressing PTGS2 and CYP450 protein expression; these results were verified by qRT-PCR, WB, and surface plasmon resonance (SPR) assays. Our experiments indicated that GQD alleviated UC in mice by systematically regulating arachidonic acid metabolism and tryptophan metabolism, supporting further research and the development of GQD as a novel drug for ameliorating UC.</p>","PeriodicalId":348,"journal":{"name":"Journal of Chromatography B","volume":"1250 ","pages":"124352"},"PeriodicalIF":2.8,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142685651","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}
Pub Date : 2024-11-06DOI: 10.1016/j.jchromb.2024.124370
Na Li , Yuchi Zhang , Mengyao Gao , Chen Yan , Yun Wei
Solvent flotation primarily relies on the variations in the activity of substances to adsorb target compounds onto the surface of bubbles, thereby facilitating the process of separation and extraction. This technology has the advantages of high separation efficiency, gentle process, and simple operation, making it widely applicable across various fields. This article reviews relevant research from the past decade to analyze the factors influencing this technology. Additionally, it provides a comprehensive overview of its applications in detecting organic matter in environmental samples and extracting bioactive compounds from natural products, while also anticipating upcoming trends in its development.
{"title":"Progress in the technology of solvent flotation","authors":"Na Li , Yuchi Zhang , Mengyao Gao , Chen Yan , Yun Wei","doi":"10.1016/j.jchromb.2024.124370","DOIUrl":"10.1016/j.jchromb.2024.124370","url":null,"abstract":"<div><div>Solvent flotation primarily relies on the variations in the activity of substances to adsorb target compounds onto the surface of bubbles, thereby facilitating the process of separation and extraction. This technology has the advantages of high separation efficiency, gentle process, and simple operation, making it widely applicable across various fields. This article reviews relevant research from the past decade to analyze the factors influencing this technology. Additionally, it provides a comprehensive overview of its applications in detecting organic matter in environmental samples and extracting bioactive compounds from natural products, while also anticipating upcoming trends in its development.</div></div>","PeriodicalId":348,"journal":{"name":"Journal of Chromatography B","volume":"1249 ","pages":"Article 124370"},"PeriodicalIF":2.8,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142646701","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":"Corrigendum to \"Pharmacokinetic and tissue distribution study of pectolinarigenin in rats using UPLC-MS/MS\" [J. Chromatogr. B 1247 (2024) 124344].","authors":"Yingying Pan, Zihan Tan, Ping Liu, Aixia Yang, Lin-Lin Chen","doi":"10.1016/j.jchromb.2024.124366","DOIUrl":"10.1016/j.jchromb.2024.124366","url":null,"abstract":"","PeriodicalId":348,"journal":{"name":"Journal of Chromatography B","volume":" ","pages":"124366"},"PeriodicalIF":2.8,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142581352","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}
Pub Date : 2024-11-01DOI: 10.1016/j.jchromb.2024.124375
Hongxin Qie , Cong Song , Yuxiang Xu , Haopeng Zhao , Wenlin Gong , Peiyuan Wang , Xiaonan Gao , Jinglin Gao , Zhangying Feng , Mingxia Wang
Furmonertinib (AST2818) is a selective epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) being developed for the treatment of patients with EGFR mutation-positive non-small cell lung cancer. Quantification of furmonertinib in plasma and cerebrospinal fluid (CSF) can be used to assess penetration of furmonertinib into the central nervous system (CNS). This paper described ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) methods for quantification of furmonertinib in human plasma and CSF. Sample separation was achieved on a Kinetex C18 column (100 mm × 2.1 mm, 2.6 μm) after simple protein precipitation with acetonitrile. The mobile phase was composed of acetonitrile and 5 mM ammonium acetate with 0.2 % formic acid in water. Quantitative ion pairs were m/z 569.3 → 72.2 for furmonertinib and m/z 526.5 → 72.2 for aumolertinib, which was used as the internal standard (IS). The calibration curves showed good linearity (r2 > 0.99) over concentration range of 0.5–200 ng/mL(plasma sample) and 0.05–30 ng/mL(CSF sample). The precision (RSD) was ≤7.86 %, and the accuracy fell within the range of 96.2 %–109.3 %, all meeting acceptance criteria. The matrix effect was from 94.3 % to 102.1 %. The recovery of analytes fell within the range of 93.3 %–98.9 %. The established analytical methods showed great sensitivity, simplicity, accuracy and reliability for the analysis of furmonertinib in human plasma and CSF. This assay would be helpful to predict the effectiveness and toxicities of furmonertinib in the pursuit of precision medicine for lung cancer patients.
{"title":"Determination of furmonertinib in human plasma and cerebrospinal fluid by UPLC-MS/MS: Application in lung cancer patients with and without brain metastasis","authors":"Hongxin Qie , Cong Song , Yuxiang Xu , Haopeng Zhao , Wenlin Gong , Peiyuan Wang , Xiaonan Gao , Jinglin Gao , Zhangying Feng , Mingxia Wang","doi":"10.1016/j.jchromb.2024.124375","DOIUrl":"10.1016/j.jchromb.2024.124375","url":null,"abstract":"<div><div>Furmonertinib (AST2818) is a selective epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) being developed for the treatment of patients with EGFR mutation-positive non-small cell lung cancer. Quantification of furmonertinib in plasma and cerebrospinal fluid (CSF) can be used to assess penetration of furmonertinib into the central nervous system (CNS). This paper described ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) methods for quantification of furmonertinib in human plasma and CSF. Sample separation was achieved on a Kinetex C<sub>18</sub> column (100 mm × 2.1 mm, 2.6 μm) after simple protein precipitation with acetonitrile. The mobile phase was composed of acetonitrile and 5 mM ammonium acetate with 0.2 % formic acid in water. Quantitative ion pairs were <em>m</em>/<em>z</em> 569.3 → 72.2 for furmonertinib and <em>m</em>/<em>z</em> 526.5 → 72.2 for aumolertinib, which was used as the internal standard (IS). The calibration curves showed good linearity (r<sup>2</sup> > 0.99) over concentration range of 0.5–200 ng/mL(plasma sample) and 0.05–30 ng/mL(CSF sample). The precision (RSD) was ≤7.86 %, and the accuracy fell within the range of 96.2 %–109.3 %, all meeting acceptance criteria. The matrix effect was from 94.3 % to 102.1 %. The recovery of analytes fell within the range of 93.3 %–98.9 %. The established analytical methods showed great sensitivity, simplicity, accuracy and reliability for the analysis of furmonertinib in human plasma and CSF. This assay would be helpful to predict the effectiveness and toxicities of furmonertinib in the pursuit of precision medicine for lung cancer patients.</div></div>","PeriodicalId":348,"journal":{"name":"Journal of Chromatography B","volume":"1248 ","pages":"Article 124375"},"PeriodicalIF":2.8,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142643553","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}
A Magnetic Molecularly Imprinted Polymer (MMIP) was developed using naringin as template molecule, acrylamide as functional monomer and polymerized by ultrasound irradiation for the adsorption of naringin. In an unexpected turn of results, the selectivity study unveiled that the synthesized MMIP exhibited a higher affinity for quercetin over naringin. Given this high selectivity, adsorption isotherm and kinetic studies were conducted for both quercetin and naringin. The adsorption isotherm indicated multilayer adsorption of the adsorbate on the adsorbent. The kinetic study showed better agreement with the pseudo-second-order kinetic model. The maximum adsorption capacity of 7.2 mg/g was achieved for quercetin at 50 mg/L and 4.9 mg/g was attained for naringin at the same concentration. Furthermore, quercetin quantification was performed by coupling MMIP with HPLC-UV, with method validation revealing the limits of detection (LOD) and quantification (LOQ) for quercetin. Additionally, agro-industrial waste onion peel, enriched with phenolic compounds such as quercetin, was subjected to solid-phase extraction using MMIP for the purification of quercetin.
{"title":"Naringin-templated magnetic molecularly imprinted polymers for selective quercetin extraction from onion peel","authors":"Vinitha Udhayabanu Govindarajan, Vaishnavi Renganathan, Meenakshi Sundaram Muthuraman","doi":"10.1016/j.jchromb.2024.124349","DOIUrl":"10.1016/j.jchromb.2024.124349","url":null,"abstract":"<div><div>A Magnetic Molecularly Imprinted Polymer (MMIP) was developed using naringin as template molecule, acrylamide as functional monomer and polymerized by ultrasound irradiation for the adsorption of naringin. In an unexpected turn of results, the selectivity study unveiled that the synthesized MMIP exhibited a higher affinity for quercetin over naringin. Given this high selectivity, adsorption isotherm and kinetic studies were conducted for both quercetin and naringin. The adsorption isotherm indicated multilayer adsorption of the adsorbate on the adsorbent. The kinetic study showed better agreement with the pseudo-second-order kinetic model. The maximum adsorption capacity of 7.2 mg/g was achieved for quercetin at 50 mg/L and 4.9 mg/g was attained for naringin at the same concentration. Furthermore, quercetin quantification was performed by coupling MMIP with HPLC-UV, with method validation revealing the limits of detection (LOD) and quantification (LOQ) for quercetin. Additionally, agro-industrial waste onion peel, enriched with phenolic compounds such as quercetin, was subjected to solid-phase extraction using MMIP for the purification of quercetin.</div></div>","PeriodicalId":348,"journal":{"name":"Journal of Chromatography B","volume":"1248 ","pages":"Article 124349"},"PeriodicalIF":2.8,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142586150","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}
Pub Date : 2024-11-01DOI: 10.1016/j.jchromb.2024.124367
Saurabh B. Ganorkar , Preeti S. Bobade , Rakesh C. Prabhu , Deepak K. Lokwani , Ranajit N. Shinde , Darshan R. Telange , Atul A. Shirkhedkar , Yvan Vander Heyden
The recent pandemic has highlighted the impact of diseases on global health and the economy. The rapid discovery of new hit molecules remains a tough challenge. Pharmaceutical impurity profiling can be linked to drug discovery through the identification of new hits from compounds identified during the analytical profiling. The present study demonstrates this linkage through the extension of the impurity (forced degradation) profiling of eltrombopag (ELT) olamine, a thrombopoietin (TPO) receptor agonist. The drug was exposed to standard degradation and the degradation products were primarily resolved and identified by UPLC-ESI-MS. This led to the identification of five forced degradation products (FDP). Thirty-three other known related substances (RS) of ELT, identified in the literature, were also considered. Molecular similarity checks were performed using Tanimoto/Jaccard's similarity searches. A set of structurally and topologically similar molecules, including ELT and 15 RS, was established and subjected to in-silico toxicity-, absorption-, distribution-, metabolism-, and elimination (ADME) predictions. The RS, predicted with similar or lower toxicity than ELT and a comparable ADME profile, were subjected to molecular docking to trace changes in TPO receptor affinity. The results indicated that five RS had a high Jaccard’s similarity with ELT and higher or comparable docking scores. These compounds, along with few other impurities were predicted to have lower toxicity, better or comparable absorption, distribution, metabolism, and also a better excretion profile than ELT. This justifies their entry as potential novel TPO receptor agonists in drug discovery.
{"title":"Extension of impurity profiling on eltrombopag olamine to in-silico predictions: An effort to exploit correlated forced degradation products and known drug-related substances in drug discovery","authors":"Saurabh B. Ganorkar , Preeti S. Bobade , Rakesh C. Prabhu , Deepak K. Lokwani , Ranajit N. Shinde , Darshan R. Telange , Atul A. Shirkhedkar , Yvan Vander Heyden","doi":"10.1016/j.jchromb.2024.124367","DOIUrl":"10.1016/j.jchromb.2024.124367","url":null,"abstract":"<div><div>The recent pandemic has highlighted the impact of diseases on global health and the economy. The rapid discovery of new hit molecules remains a tough challenge. Pharmaceutical impurity profiling can be linked to drug discovery through the identification of new hits from compounds identified during the analytical profiling. The present study demonstrates this linkage through the extension of the impurity (forced degradation) profiling of eltrombopag (ELT) olamine, a thrombopoietin (TPO) receptor agonist. The drug was exposed to standard degradation and the degradation products were primarily resolved and identified by UPLC-ESI-MS. This led to the identification of five forced degradation products (FDP). Thirty-three other known related substances (RS) of ELT, identified in the literature, were also considered. Molecular similarity checks were performed using Tanimoto/Jaccard's similarity searches. A set of structurally and topologically similar molecules, including ELT and 15 RS, was established and subjected to in-silico toxicity-, absorption-, distribution-, metabolism-, and elimination (ADME) predictions. The RS, predicted with similar or lower toxicity than ELT and a comparable ADME profile, were subjected to molecular docking to trace changes in TPO receptor affinity. The results indicated that five RS had a high Jaccard’s similarity with ELT and higher or comparable docking scores. These compounds, along with few other impurities were predicted to have lower toxicity, better or comparable absorption, distribution, metabolism, and also a better excretion profile than ELT. This justifies their entry as potential novel TPO receptor agonists in drug discovery.</div></div>","PeriodicalId":348,"journal":{"name":"Journal of Chromatography B","volume":"1248 ","pages":"Article 124367"},"PeriodicalIF":2.8,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142638171","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}
Pub Date : 2024-11-01DOI: 10.1016/j.jchromb.2024.124339
Samineh Raha , Ali Akbar Fathi , Mohammad Reza Afshar Mogaddam , Ali Shahedi-Hodjaghan , Mir Ali Farajzadeh , Mohamadbagher Hosseini , Maryam Khoubnasabjafari , Vahid Jouyban-Gharamaleki , Abolghasem Jouyban
A cobalt-based metal–organic framework and graphene oxide were combined to prepare a new nanocomposite for extracting of caffeine from exhaled breath condensate (EBC) samples. Dispersive micro solid phase extraction of caffeine was conducted using the nanocomposite as a sorbent by adding 10 mg of it to the sample solution and vortexing for 3 min. After extracting of the analyte, it was eluted using the mobile phase. The analyte was then analyzed using high performance liquid chromatography-photodiode array detector. Under optimal conditions, the limit of detection, limit of quantification, and linear range of the calibration curve were found to be 1.7, 5.9, and 10–500 µg/L, respectively. To assess the precision of the method, five replicates of standard solutions containing caffeine at two different concentration levels (50 and 100 µg/L) were tested. The relative standard deviations for intra- and inter-day precisions ranged from 4.3 to 6.8 %. The applicability of the method was demonstrated by analyzing the samples obtained from premature infants undergoing caffeine treatment and caffeine concentrations were 4.9 ± 0.6, 2.7 ± 0.2 µg/L in the EBC samples of who were under treatment by a 5-mg dose. Also, caffeine concentrations were 5.9 ± 0.3 and 18 ± 0.6 µg/L in the the infants who obtained the 10-mg and 25-mg doses, respectively. The results indicated a satisfactory, extraction recovery of 86 % showcasing the method’s reliability and effectiveness in analyzing real samples.
{"title":"Heteroatom cobalt-based metal-organic framework and reduced graphene oxide nanocomposite for dispersive solid phase extraction of caffeine from exhaled breath condensate samples of premature infants prior to HPLC-PDA","authors":"Samineh Raha , Ali Akbar Fathi , Mohammad Reza Afshar Mogaddam , Ali Shahedi-Hodjaghan , Mir Ali Farajzadeh , Mohamadbagher Hosseini , Maryam Khoubnasabjafari , Vahid Jouyban-Gharamaleki , Abolghasem Jouyban","doi":"10.1016/j.jchromb.2024.124339","DOIUrl":"10.1016/j.jchromb.2024.124339","url":null,"abstract":"<div><div>A cobalt-based metal–organic framework and graphene oxide were combined to prepare a new nanocomposite for extracting of caffeine from exhaled breath condensate (EBC) samples. Dispersive micro solid phase extraction of caffeine was conducted using the nanocomposite as a sorbent by adding 10 mg of it to the sample solution and vortexing for 3 min. After extracting of the analyte, it was eluted using the mobile phase. The analyte was then analyzed using high performance liquid chromatography-photodiode array detector. Under optimal conditions, the limit of detection, limit of quantification, and linear range of the calibration curve were found to be 1.7, 5.9, and 10–500 µg/L, respectively. To assess the precision of the method, five replicates of standard solutions containing caffeine at two different concentration levels (50 and 100 µg/L) were tested. The relative standard deviations for intra- and inter-day precisions ranged from 4.3 to 6.8 %. The applicability of the method was demonstrated by analyzing the samples obtained from premature infants undergoing caffeine treatment and caffeine concentrations were 4.9 ± 0.6, 2.7 ± 0.2 µg/L in the EBC samples of who were under treatment by a 5-mg dose. Also, caffeine concentrations were 5.9 ± 0.3 and 18 ± 0.6 µg/L in the the infants who obtained the 10-mg and 25-mg doses, respectively. The results indicated a satisfactory, extraction recovery of 86 % showcasing the method’s reliability and effectiveness in analyzing real samples.</div></div>","PeriodicalId":348,"journal":{"name":"Journal of Chromatography B","volume":"1248 ","pages":"Article 124339"},"PeriodicalIF":2.8,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142553164","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}
Pub Date : 2024-11-01DOI: 10.1016/j.jchromb.2024.124353
Lifeng Zhao , Xin Yu , Siyang Wu , Kexin Xia , Yuyan Wang , Peichong Qin , Zhishan Huang , Chen Kang , Zheng Yuan , Yingfei Li
Licorice, known as the “elder statesman,” is commonly used in traditional Chinese medicine (TCM) formulations. This study aims to establish a workflow combining animal and in silico experiments to elucidate the mechanisms of TCMs at both qualitative and quantitative levels. UPLC-Q-TOF-MS/MS was employed to qualitatively characterize the total components of honey-fried licorice and the plasma components after oral administration in Beagle dogs. A UPLC-Q-Trap-MS/MS method was developed for the pharmacokinetic study of honey-fried licorice components in Beagle dog plasma. Network pharmacology and molecular docking were utilized to explore the primary functional targets and pathways. In total, we identified 68 constituents in honey-fried licorice, with 28 detected in Beagle dog plasma, and 18 of them, mainly belong to flavonoids and terpenoids, showing significant exposure. The plasma pharmacokinetic study of these 18 constituents revealed that compounds like liquiritin, glycyrrhizic acid, licoricesaponin G2, and glycyrrhetic acid-3-o-glucuronide had significant exposure. Network pharmacology and molecular docking analyses identified MAPK3, PIK3CB, PIK3CA, RAF1, and EGFR as the main targets of the active constituents of honey-fried licorice, involved in pathways such as the Ras signaling pathway, human cytomegalovirus infection, and the MAPK signaling pathway. This study provides a comprehensive profile and pharmacokinetic characteristics of honey-fried licorice, offering insights into its pharmacological, toxicological, and clinical aspects. The established workflow can serve as a standard for investigating other TCMs.
{"title":"Pharmacokinetic profiling and network pharmacology of honey-fried Licorice: An Integrative workflow to study traditional Chinese medicines (TCMs)","authors":"Lifeng Zhao , Xin Yu , Siyang Wu , Kexin Xia , Yuyan Wang , Peichong Qin , Zhishan Huang , Chen Kang , Zheng Yuan , Yingfei Li","doi":"10.1016/j.jchromb.2024.124353","DOIUrl":"10.1016/j.jchromb.2024.124353","url":null,"abstract":"<div><div>Licorice, known as the “elder statesman,” is commonly used in traditional Chinese medicine (TCM) formulations. This study aims to establish a workflow combining animal and in silico experiments to elucidate the mechanisms of TCMs at both qualitative and quantitative levels. UPLC-Q-TOF-MS/MS was employed to qualitatively characterize the total components of honey-fried licorice and the plasma components after oral administration in Beagle dogs. A UPLC-Q-Trap-MS/MS method was developed for the pharmacokinetic study of honey-fried licorice components in Beagle dog plasma. Network pharmacology and molecular docking were utilized to explore the primary functional targets and pathways. In total, we identified 68 constituents in honey-fried licorice, with 28 detected in Beagle dog plasma, and 18 of them, mainly belong to flavonoids and terpenoids, showing significant exposure. The plasma pharmacokinetic study of these 18 constituents revealed that compounds like liquiritin, glycyrrhizic acid, licoricesaponin G2, and glycyrrhetic acid-3-o-glucuronide had significant exposure. Network pharmacology and molecular docking analyses identified MAPK3, PIK3CB, PIK3CA, RAF1, and EGFR as the main targets of the active constituents of honey-fried licorice, involved in pathways such as the Ras signaling pathway, human cytomegalovirus infection, and the MAPK signaling pathway. This study provides a comprehensive profile and pharmacokinetic characteristics of honey-fried licorice, offering insights into its pharmacological, toxicological, and clinical aspects. The established workflow can serve as a standard for investigating other TCMs.</div></div>","PeriodicalId":348,"journal":{"name":"Journal of Chromatography B","volume":"1248 ","pages":"Article 124353"},"PeriodicalIF":2.8,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142611269","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}
Pub Date : 2024-11-01DOI: 10.1016/j.jchromb.2024.124334
Tianmei Niu , Jiaxin Wang , Liying Xun , Bingqing Zheng , Zhipeng Deng , Zhi Chen , Kaijie Jia , Pan Zhao , Qitao Zhao
The Cortex Juglandis Mandshuricae (CJM) has the efficacy of penetrating the liver meridian, removing heat and dampness, and alleviating the liver, which corresponds to the pathogenesis of alcoholic fatty liver disease (AFLD) with damp heat accumulation. Modern research has shown that total flavonoids from Cortex Juglandis Mandshuricae (TFC) have hepatoprotective, antioxidant and antitumour pharmacological effects. However, there is no any investigation on the mechanism of TFC improving AFLD. In this work, a valid strategy combining UPLC-Q-Exactive Orbitrap-MS, network pharmacology and in vitro cellular experimental validation is proposed to predict the targets and pathways of TFC to ameliorate AFLD and to explore its mechanism of action. As a result, 26 flavonoids and 182 targets linked to TFC and AFLD were identified. These compounds realize their critical targets via various signaling pathways and perform multiple biological functions on the basis of the constructed compound-disease target networks. In vitro experiments demonstrated TFC had a protective impact on ethanol-treated L02 cells to a certain extent and could diminished lipid accretion. In addition, RT-qPCR and western blot results illustrated that TFC could regulate the expression of PPARα, CPT-1, SREBP-1c and FAS, and inhibit alcohol-induced lipid accumulation in L02 cells thereby alleviating AFLD. The present study further provides experimental justification for TFC to ameliorate AFLD in practical applications.
{"title":"Deciphering the impact and mechanism of total flavonoids from Cortex Juglandis Mandshuricae on alcoholic fatty liver employing LC-MS/MS, network pharmacology analysis and in vitro validation","authors":"Tianmei Niu , Jiaxin Wang , Liying Xun , Bingqing Zheng , Zhipeng Deng , Zhi Chen , Kaijie Jia , Pan Zhao , Qitao Zhao","doi":"10.1016/j.jchromb.2024.124334","DOIUrl":"10.1016/j.jchromb.2024.124334","url":null,"abstract":"<div><div>The Cortex Juglandis Mandshuricae (CJM) has the efficacy of penetrating the liver meridian, removing heat and dampness, and alleviating the liver, which corresponds to the pathogenesis of alcoholic fatty liver disease (AFLD) with damp heat accumulation. Modern research has shown that total flavonoids from Cortex Juglandis Mandshuricae (TFC) have hepatoprotective, antioxidant and antitumour pharmacological effects. However, there is no any investigation on the mechanism of TFC improving AFLD. In this work, a valid strategy combining UPLC-Q-Exactive Orbitrap-MS, network pharmacology and in vitro cellular experimental validation is proposed to predict the targets and pathways of TFC to ameliorate AFLD and to explore its mechanism of action. As a result, 26 flavonoids and 182 targets linked to TFC and AFLD were identified. These compounds realize their critical targets via various signaling pathways and perform multiple biological functions on the basis of the constructed compound-disease target networks. In vitro experiments demonstrated TFC had a protective impact on ethanol-treated L02 cells to a certain extent and could diminished lipid accretion. In addition, RT-qPCR and western blot results illustrated that TFC could regulate the expression of PPARα, CPT-1, SREBP-1c and FAS, and inhibit alcohol-induced lipid accumulation in L02 cells thereby alleviating AFLD. The present study further provides experimental justification for TFC to ameliorate AFLD in practical applications.</div></div>","PeriodicalId":348,"journal":{"name":"Journal of Chromatography B","volume":"1248 ","pages":"Article 124334"},"PeriodicalIF":2.8,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142602251","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}
Pub Date : 2024-11-01DOI: 10.1016/j.jchromb.2024.124359
Danhong Shen , Wei Chen , Jindi Liu , Yanhua Liu , Hongjun Shi
Methylmalonic acid (MMA) is a reverse biomarker of vitamin B12 that is increasingly utilized in clinical practice. However, its low sensitivity and susceptibility to strong interference from isomer present chromatographic challenges. We have developed a rapid derivatization method for plasma MMA at room temperature, converting it to the corresponding 2,2,2-trifluoroethylamide derivative using N-(3-dimethylaminopropyl)-N’-ethylcarbodiimide hydrochloride (EDC) and 2,2,2-trifluoroethylamine hydrochloride (TFEA). Amidization was completed within 10 min, followed by protein precipitation extraction of the amides with trichloroacetic acid for Liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis. This technique notably enhanced the signal-to-noise ratio of MMA in chromatography. The derivatized MMA exhibited excellent linearity within a concentration range of 42.4–2711.9 nmol/L, with a correlation coefficient (R2) of 0.9990. The intraday and interday precision of replicate measurements ranged from 2.4 % to 4.4 % and 2.6 % to 2.8 %, respectively, while the recovery fell between 97.9 % and 100.1 %.
{"title":"Quantitative analysis of methylmalonic acid in human plasma by LC-MS/MS after derivatization","authors":"Danhong Shen , Wei Chen , Jindi Liu , Yanhua Liu , Hongjun Shi","doi":"10.1016/j.jchromb.2024.124359","DOIUrl":"10.1016/j.jchromb.2024.124359","url":null,"abstract":"<div><div>Methylmalonic acid (MMA) is a reverse biomarker of vitamin B12 that is increasingly utilized in clinical practice. However, its low sensitivity and susceptibility to strong interference from isomer present chromatographic challenges. We have developed a rapid derivatization method for plasma MMA at room temperature, converting it to the corresponding 2,2,2-trifluoroethylamide derivative using N-(3-dimethylaminopropyl)-N’-ethylcarbodiimide hydrochloride (EDC) and 2,2,2-trifluoroethylamine hydrochloride (TFEA). Amidization was completed within 10 min, followed by protein precipitation extraction of the amides with trichloroacetic acid for Liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis. This technique notably enhanced the signal-to-noise ratio of MMA in chromatography. The derivatized MMA exhibited excellent linearity within a concentration range of 42.4–2711.9 nmol/L, with a correlation coefficient (R<sup>2</sup>) of 0.9990. The intraday and interday precision of replicate measurements ranged from 2.4 % to 4.4 % and 2.6 % to 2.8 %, respectively, while the recovery fell between 97.9 % and 100.1 %.</div></div>","PeriodicalId":348,"journal":{"name":"Journal of Chromatography B","volume":"1248 ","pages":"Article 124359"},"PeriodicalIF":2.8,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142586148","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}
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