ANALYTICAL CHEMISTRY
·
2025
·
IF 6.7
Tian Tian,Xi Chen,Li Liu,Xueqi Liang,Xiaojun Deng
The current limited understanding of small bioactive peptide metabolism hinders effective doping control. A primary challenge lies in distinguishing suspicious features from extensive mass spectral datasets contaminated by biological matrix interference and background noise. In this study, we introduce a strategy integrating in silico prediction and nontargeted data mining to achieve more comprehensive metabolic profiling through ultrahigh-performance liquid chromatography–high-resolution mass spectrometry (UHPLC-HRMS). The strategy operates by identifying and applying chemical similarity (CSIM) rules of peptides (such as LC/MS behaviors and specific biotransformation) to mine unknown metabolites. With this strategy, a semiautomated workflow utilizing computational software and custom script was constructed and applied to the human liver microsomal metabolism of two significant kisspeptin analogues with doping potential (TAK-448 and TAK-683). The characteristic behaviors induced by CSIM enabled effectively in-depth data mining from redundant background signals, leading to the identification of 13 metabolites (three were validated via synthetic standards) and two uncommon biotransformation pathways (N-terminal vinylation and N-terminal carboxylation) for both investigated compounds. Notably, the two biotransformation pathways offered an innovative perspective on small peptide metabolism, which was further confirmed in rats, and produced two promising long-term metabolites for monitoring doping abuse. Further drug activity evaluation indicated higher or retained performance-enhancing effects of these metabolites, alerting doping control subjects to pay attention to more information. The study provided the first comprehensive characterization of the metabolic profiles of TAK-448 and TAK-683, while also offering an effective tool for metabolism research on small peptide doping agents.
研究领域:
分析化学
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药学
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代谢组学
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兴奋剂检测
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生物信息学
✓ 已验证
DOI
PubMed
高影响因子
MICROCHEMICAL JOURNAL
·
2026
·
IF 5.2
Yue Sun,Juntao Wang,Shiqiong Chen,Qin Yang,Sixin Liu,Congfa Li
This study presents a comprehensive characterization and comparison of polyphenols in Alpiniae oxyphyllae fructus extracted using ultrasound-assisted deep eutectic solvents (DESs) versus traditional solvents. The contents of total polyphenols in Choline chloride -malic acid (ChCl-MA) (1:1) , ChCl-MA (1:2) , L-proline-Lactic acid (Pro-LA) (1:1) , Pro-LA (1:3) , and L-proline-citric acid (Pro-CA) (1:3) extracts were the highest, ranging from 17.67 to 19.37 mg/g, and were significantly higher than those in water extract (10.35 mg/g) and ethanol extract (14.78 mg/g) ( p < 0.05). Pro-LA extract exhibited high levels of 3,4-dihydroxybenzoic acid and protocatechualdehyde, and possessed strong antioxidant activity. Density functional theory (DFT) calculations indicated that the mechanism of DESs' efficient extraction of polyphenols was mainly reflected in the unique structural configuration of Pro-LA, which facilitated the formation of strong hydrogen bonds with the hydroxyl functional groups of polyphenols, enhancing the intermolecular interaction, and thus improving the extraction efficiency. Our study provided a novel approach for the efficient extraction of plant polyphenols.
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DOI
高影响因子
JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
·
2024
·
IF 3.1
Baoyan Ding,Wei Meng,Xiaoling Zang,Zhihua Lv
A small molecule, (S)-ethyl 1-(3-(4-chlorophenoxy)-2-hydroxypropyl)-3-(4-methoxyphenyl)-1H-pyrazole-5-carboxylate (SEC), has been reported to be capable of suppressing metastasis of prostate cancer (PCa) cells. In this study, SEC was used to study the metabolic responses of PCa cell lines (LNCaP, PC3, and DU145) with different metastatic potential and the alterations of mTOR, p-mTOR, AMPK, and p-AMPK levels, when the PCa cells were inhibited. The ultra-high performance liquid chromatography-high resolution mass spectrometry (UHPLC-HRMS)-based analysis showed that SEC induced the decreases of intracellular metabolites including glutamic acid, glutamine, and histidine (LNCaP); creatinine, citric acid/isocitric acid, and aspartic acid (PC3); and spermidine, S-hydroxymethylglutathione, LPE (20:3), and palmitic amide (DU145), and the increases of intracellular LPC (18:0) (LNCaP); tyrosine, pyroglutamic acid/pyrroline hydroxycarboxylic acid (PC3); and tyrosine, phenylalanine, phenylacetylglycine, spermine, histidine, and choline (DU145). SEC also caused the decrease of extracellular N1-acetylspermidine (LNCaP), erythronic acid/threonic acid (PC3 and DU145), and nicotinic acid/picolinic acid (DU145), and the increase of extracellular 5’-methylthioadenosine (DU145). High metastatic PC3 and DU145 cells exhibited changes in aromatic amino acid metabolism including tyrosine metabolism, phenylalanine, tyrosine, and tryptophan metabolism, and phenylalanine metabolism (PC3 and DU145), TCA cycle (PC3), arginine and proline metabolism, and glycerophospholipid metabolism (DU145), different from the low metastatic LNCaP cells, which had changes in alanine, aspartate, and glutamate metabolism, and arginine biosynthesis. In addition, the levels of p-mTOR and p-AMPK were shown to be obviously downregulated and upregulated, respectively, in high metastatic PC3 and DU145 cells upon SEC inhibition, while this behavior was not detected in LNCaP cells.
研究领域:
肿瘤学
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代谢组学
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药理学
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产品关联
DOI
PubMed
高影响因子
CHIRALITY
·
2026
·Vol. 38
·期 7
·e70112
·
IF 2.4
Shuyun Xiao,Hang Shi,Shuyi Song,Jun Zhe Min
Sake, a fermented alcoholic beverage made from rice and Aspergillus oryzae through microbial fermentation, contains thiol compounds that are the primary source of its distinctive sweet aroma. However, to date, there has been no report on the detection of chiral thiol compounds in sake. This study introduces a novel UHPLC-HRMS method utilizing the (R)-(5-(3-isothiocyanatopyrrolidin-1-yl)-5-oxopentyl) triphenylphosphonium (NCS-OTPP) chiral mass spectrometry probe for the simultaneous detection of five DL-thiol compounds in sake. Separation was achieved using a YMC Triart C18 column (2.0 × 150 mm, 1.9 μm), employing an isocratic elution method to isolate DD/LL-GSH, γ-L-Glu-L-Cys, DL-Cys, DL-Hcy, and DL-Ac-Cys. The method demonstrated excellent linearity ( R 2 ≥ 0.9992), intraday precision (0.43%–13.18%), and an average recovery rate of 91.62%–110.40%. A comparative analysis of DL-thiol compound content in seven different types of sake from various countries and manufacturers revealed the presence of five chiral thiol compounds—LL-GSH, γ-L-Glu-L-Cys, DL-Cys, DL-Hcy, and L-Ac-Cys—across Japanese and Korean sake, with L-Cys being the most abundant and D-Ac-Cys the least. Notably, γ-L-Glu-L-Cys was detected only in two types of Korean sake and absent in Japanese sake. Additionally, the study investigated the metabolic kinetics of chiral thiol compounds in human urinary specimens after alcohol ingestion, constructing a metabolic fitting curve. The peak concentrations of DL-Cys, DL-Hcy, and LL-GSH were attained 15 min following consumption, with slow clearance, returning to baseline at 60 min. The metabolic fitting curve effectively captures the dynamic changes in urinary metabolism. This research presents a new method for detecting chiral thiol compounds in sake and monitoring urinary metabolism after alcohol consumption.
✓ 已验证
DOI
PubMed
高影响因子
FOOD RESEARCH INTERNATIONAL
·
2026
·
IF 8.8
Kangyan Zhang,Siyu Wang,Huiru Zhang,Jing Ming,Wanjun Long,Haiyan Fu
Artemisiae Argyi Folium (AAF) is a medicinal and edible herb whose quality is dependent on its geographical origin and aging years. This study employed untargeted metabolomics based on GC–MS and UHPLC-HRMS to identify its geographical origin and aging years. First, we employed our proprietary AntDAS platform to fully analyze the mass spectrometry data and screen for key differential metabolites. Analysis identified 58 geographical origin-related metabolites (35 non-volatile and 23 volatile). Notably, the chemical profiles of the two Dao-di production regions differed markedly. Samples from Nanyang (Henan) were characterized by high abundances of endo -borneol, terpinen-4-ol, eucalyptol, 3,4-dicaffeoylquinic acid, phellopterin, and quercetin, whereas these compounds were found in low abundance in samples from the other Dao-di production region, Qichun (Hubei). Furthermore, 27 metabolites with aging-year differences were identified, comprising 18 non-volatile and 9 volatile compounds, and the aged AAF compared to fresh AAF showed significantly enriched chemical components. Regarding the aging effect, the contents of eucalyptol and 5-methyl-decane were highest in the 5-year samples. Endo -borneol showed higher levels in both 1-year and 5-year samples, with its content in 3-year samples being intermediate. In contrast, n-hexadecanoic acid and phytol were more abundant in samples aged for over 5 years. Finally, using these differential metabolites, OPLS-DA models achieved 100.0% accuracy in geographical origin classification and over 94.4% accuracy for aging year discrimination. This study provides a chemical basis for the geographical origin traceability and aging year identification of food-drug homologous products.
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产品关联
DOI
高影响因子
INDUSTRIAL CROPS AND PRODUCTS
·
2023
·
IF 5.9
Jia-Ni Zhang,Meng-Han Ma,Xing-Ling Ma,Feng-Lian Ma,Qing-Yu Du,Jia-Nan Liu,Xing-Cai Wang,Qi-Peng Zhao,Yong-Jie Yu,Yuanbin She
The effect of drying methods on the variations of volatile, semi-volatile, and involatile compounds in Elaeagnus angustifolia L. (E.A.) flower was comprehensively investigated by using gas chromatography-mass spectrometry (GC-MS) and ultrahigh performance liquid chromatography-high resolution mass spectrometry (UHPLC-HRMS) based untargeted metabolomics combined with our recently developed automatic data analysis software AntDAS for the first time. About 21 volatile compounds, 44 semi-volatile compounds, and 17 involatile compounds were identified and showed significant differences among drying methods. Chemometric methods like principal components analysis (PCA), and partial least squares-discriminant analysis (PLS-DA) were used in combination with heatmap analysis to reveal the relationship between compound compositions and drying methods. Finally, it was concluded that room-temperature drying is more conducive to preserving volatile compounds in E.A. flower, and hot air drying is better for preserving semi-volatile and involatile compounds. This work can provide guidelines for industrial processes of E.A. flower.
研究领域:
植物学
·
分析化学
·
药用植物研究
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产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）