Analytical Methods
·
2022
·Vol. 14
·期 47
·4990-5000
·
IF 3.532
Xiangyu Zhang,Yaojuan Chu,Mengli Wang,Yingying Shi,Lihua Zuo,Zhuolun Li,Jiyun Liu,Jian Kang,Shuzhang Du,Bing Li,Zhi Sun,Xiaojian Zhang
Mai-Luo-Shu-Tong pill is an effective traditional Chinese medicine formula for the treatment of superficial thrombophlebitis, but it was insufficiently chemically scrutinized. In this study, the mass spectral data of Mai-Luo-Shu-Tong pill were acquired by ultra-high performance liquid chromatography coupled with Q Exactive hybrid Quadrupole-Orbitrap high resolution mass spectrometry. Then, a data mining strategy combining multiple data processing methods was used to identify chemical constituents in Mai-Luo-Shu-Tong pill by constructing a database of precursor ions and summarizing the mass spectral fragmentation behaviors. As a result, a total of 211 compounds including 70 flavonoids, 56 terpenoids, 37 phenolic acids and 48 others were identified in positive and negative ion modes. Among them, 66 compounds have passed comparison verification with reference standards, 145 compounds were identified based on the data mining strategy combining the characteristic cleavage behaviour of homologous compounds and fragment ions and 4 compounds were potentially new compounds. This study provides a database for quality evaluation and further study of Mai-Luo-Shu-Tong pill in vivo. Moreover, it provides a reference for the characterization of the chemical constituents of other traditional Chinese medicine formulae.
研究领域:
中药化学
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分析化学
·
药学
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DOI
高影响因子
CURRENT DRUG METABOLISM
·
2021
·Vol. 22
·期 1
·70-82
·
IF 3.731
Zuo Lihua,Li Jia,Xue Lianping,Jia Qingquan,Li Zhuolun,Zhang Mengya,Zhao Mengfan,Wang Mengli,Kang Jian,Du Shuzhang,Sun Zhi
Background: Alpiniae oxyphyllae Fructus (AOF), a traditional Chinese medicine (TCM), is widely used in the treatment of urinary, gastrointestinal and neurologic diseases in China. Although terpenoids are the main active ingredients of AOF, there are few researches on their pharmacokinetics
and metabolism. Methods: In this study, a sensitive, rapid, accurate and novel ultra high performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method was established to evaluate the pharmacokinetic behavior of five terpenoids (oxyphyllenodiol B, (4S* ,5E,10R*)-7-oxo-tri-nor-eudesm-5-en-4β-ol,
7-epi-teucrenone, (+)- (4R,5S,7R)-13-hydroxynootkatone, (E)-labda-12,14-dien-15(16)-olide-17-oic acid) in rats after oral administration of AOF extracts. 27 metabolic metabolites of the five terpenoids were identified by ultra high performance liquid chromatography -Q Exactive hybrid quadrupole-orbitrap
high-resolution accurate mass spectrometry (UHPLC-Q-Orbitrap HRMS) based on precise mass and fragment ions. Results: The established pharmacokinetic analysis method showed good linearity over a wide concentration range, and the lower quantitative limit (LLOQ) ranged from 0.97 to 4.25
ng/mL. Other validation parameters were within the acceptable range. In addition, 27 metabolites were identified in plasma, urine and feces samples, and the metabolic pathways of five terpenoids were mainly focused on glucoside conjugation, dehydration, desaturation and glycine conjugation.
Conclusion: This is the first study on the pharmacokinetics and metabolism of five terpenoids in AOF, illuminating the disposal process of terpenoids in vivo. It was expected that the results of this study would provide some references for the apprehension of the action mechanism and
the further pharmacological study of five terpenoids in AOF.
研究领域:
中药学
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分析化学
·
药理学
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DOI
高影响因子
Heliyon
·
2024
·
IF 3.4
Ruijie Li,Haoliang Ke,Pan Liu,Qian Yang,Yuxin Li,Longzhu Ke,Xiuping Wang,Chaoyan Wu,Yingwen Zhang
Ethnopharmacological relevance Yiai Fuzheng formula (YAFZF), as a Traditional Chinese Medicine (TCM) prescription, has been used widely at Zhongnan Hospital of Wuhan University for its therapeutic effects and high safety on triple-negative breast cancer (TNBC). Objective In this study, we employed ultra-high-performance liquid chromatography-quadrupole/orbitrap high-resolution mass spectrometry (UPLC-Q-Orbitrap-HRMS), network pharmacology, and experimental validation to elucidate the underlying action mechanism of YAFZF in the treatment of TNBC. Methods The key active ingredients in YAFZF were analyzed using UPLC-Q-Orbitrap-HRMS, and then the potential components, target genes and signalling pathways of YAFZF were predicted using the network pharmacological method. We then used molecular docking to visualize the combination characteristics between major active components and macromolecules in the crucial pathway. In vitro experiments were conducted to investigate the inhibitory effects of YAFZF treatment on the cell viability, invasion, and migration of 4T1 and MDA-MB-231 cells. The xenograft TNBC models were constructed using female Balb/c mice, and their body weights, tumour volumes, and weights were monitored during YAFZF treatment. Quantitative real-time PCR (qRT-PCR), Hematoxylin-eosin (HE), immunohistochemistry (IHC) staining, Western blot (WB), and terminal deoxynucleotidyl transferase (TdT)-dUTP nick-end labeling (TUNEL) staining were used for further experimental validation. Results Based on UPLC-Q-Orbitrap-HRMS and network pharmacology analysis, 6 major bioactive components and 153 intersecting genes were obtained for YAFZF against TNBC. Functional enrichment analysis identified that the phosphatidylinositol 3-kinase (PI3K)-protein kinase B (Akt) signalling pathway might be the mechanism of action of YAFZF in the treatment of TNBC. Molecular docking results suggested that the main active compounds in YAFZF had strong binding energies with the proteins in the PI3K/Akt pathway. In vitro experiments showed that YAFZF inhibited the cell viability, invasion, and migration abilities of TNBC cells. Animal experiments confirmed that YAFZF treatment suppressed tumour cell proliferation and increased apoptotic cells. PCR, HE, WB, and IHC results indicated that YAFZF could suppress xenograft tumour metastases by inhibiting the PI3K/AKT/mTOR pathway regulating the epithelial-mesenchymal transition (EMT) process. Conclusion YAFZF therapy showed its potential for reducing proliferation, invasion, and migration abilities, increasing apoptosis of TNBC cells. Furthermore, YAFZF treated TNBC by inhibiting xenograft tumour distant metastases via the regulation of EMT by the PI3K/Akt/mTOR pathway, suggesting that it may be useful as an adjuvant treatment.
研究领域:
药理学
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肿瘤学
·
中医药
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分子生物学
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癌症研究
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
·
2021
·
IF 3.935
Qingkun Ma,Chao Qi,Xi-Ling Li,Qing Shi,Chun-Yan Xu,Toufeng Jin,Jun Zhe Min
A high-sensitivity and -selectivity mass spectrometry derivatization reagent, ( R )-(5-(3-isothiocyanatopyrrolidin-1-yl)-5-oxopentyl) triphenylphosphonium (NCS-OTPP), was developed for the enantiomeric separation of chiral thiol compounds as prospectively important diagnostic markers for oxidative stress-related diseases. Complete separation of GSH, DL-Cys, and DL-Hcy was achieved. The parent ions of all derivatives had a fragment of m/z 473.18 and a structure of m/z 75.95 (R-S = C-S-R’), conducive to qualitative and quantitative analysis. Good linear relationships were obtained for all analytes ( R 2 ≥ 0.9995). The intra-day and inter-day precision were 0.82–5.16 % and 1.02–4.18 % in saliva, and 0.81–3.45 % and 0.99–6.47 % in urine, with mean recoveries of 83.31–105.66 % and 84.09–101.11 %, respectively. The limit of detection ( S/N = 3) was 19.20–57.60 nM. Free and total GSH, DL-Cys, and DL-Hcy were detected simultaneously in saliva and urine from 10 volunteers in the normal, stressed, and stable states by UHPLC-Q-Orbitrap HRMS . The thiol compounds were quantitatively related to oxidative stress state changes.
研究领域:
分析化学
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医学
·
生物化学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY
·
2025
·
IF 5.4
Wei Dai,Liping Dai,Tao Su,Qin Lin,Zhiwen Lin,Shuxin Ye,Peihao Xu,Hongfeng Chen,Xilong Zheng
A green ultrasound-assisted deep eutectic solvent (UAE–DES) method was optimised for extracting flavonoid enzyme inhibitors from Blumea aromatica. Optimal conditions (choline chloride-1,4-butanediol 1:3 molar ratio, 43% water content, 50 mL/g liquid-to-solid ratio, 80 °C ultrasound for 48 min) yielded 3.15% total flavonoids, 45.2% higher than 50% ethanol extraction. Scanning electron microscopy confirmed cell wall disruption. The UAE–DES extract showed the strongest enzyme inhibition among all extracts tested (IC50 35.872 ± 0.294 µg/mL for α-glucosidase, 9.126 ± 0.285 μg/mL for tyrosinase), though the α-glucosidase inhibition was much weaker than acarbose, while tyrosinase inhibition was comparable to kojic acid. Six flavonoids were identified via UPLC-Q-Orbitrap HRMS, including scutellarein and corylin. Molecular docking revealed strong binding affinities (≤ −5 kcal/mol), with corylin showing the highest binding to both enzymes through hydrogen bonds and van der Waals interactions. This approach supports sustainable discovery of natural enzyme inhibitors for antidiabetic and skin-whitening applications.
研究领域:
植物化学
·
酶学
·
绿色化学
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药学
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分析化学
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产品关联
DOI
PubMed
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
·
药理学
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产品关联
DOI
PubMed
高影响因子
FOOD RESEARCH INTERNATIONAL
·
2022
·
IF 7.425
Yueying Jin,Shengyu Cheng,Ruobai Liu,Chenglong Yu,Lingli Zhang,Xi-Ling Li,Guanghai Yan,Mingyu Zheng,Jun Zhe Min
Lurong Dabu decoction (LRDBD) is an effective traditional Chinese Korean ethnic medicine prescription composed of eight herbs, which is used for treating asthma. However, its material basis has not been studied yet. Herein, the use of a new and highly sensitive UHPLC–Q Exactive Orbitrap–HRMS technique is proposed for the high-resolution and accurate identification of the material basis of LRDBD. We identified 122 compounds belonging to different groups in LRDBD. Among these, 23 ingredients produced by decoction were identified and compared with 8 single herb compounds. Moreover, 39 other significantly different compounds were identified. Additionally, 29 absorbed prototype components and 35 metabolites were identified in rat plasma. Half of the prototype components were originated from antler velvet, it has corroborated the compatibility theory of Sasang medicine. To the best of our knowledge, the material basis of LRDBD was characterized for the first time. Our findings provide basic data and a method for further discovering potential drug targets and revealing the action mechanism of LRDBD in asthma treatment.
研究领域:
药理学
·
分析化学
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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.
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DOI
PubMed
高影响因子
JOURNAL OF CHROMATOGRAPHY A
·
2025
·
IF 4
Tao Yang,Xinling Li,Jianhua Tan,Wenyao Liang,Xianzhi Peng
Sulfate and sulfonate compounds are extensively used as anionic surfactants in personal care products (PCPs), which might pose adverse potential to human health. However, available research mostly identified certain subsets of sulfated and sulfonated surfactants based on target analysis. In this study, we developed a comprehensive nontarget strategy for identification of sulfated and sulfonated surfactants in PCPs using UHPLC HRMS supplemented by an in-lab R script based on characteristic fragment ions and sulfur isotope patterns. A total of 20 sulfate and 12 sulfonate surfactants of confidence level 3 and above were identified in the range of alkyl chain length from C12 to C26 with 0–7 ethoxy groups and molecular weights of 200–600 Da in the PCP samples. The sulfates included 4 alkyl sulfates and 16 alkyl ether sulfates. In addition to commonly reported 4 alkyl benzene sulfonates, this study identified eight sulfonate surfactants for the first time, which were 3 alkyl sulfonates, 3 methyl ammonium sulfonates, and 2 bis-sulfonate sulfonates in the PCPs. Interestingly, 22 sulfate and sulfonate compounds were identified in the negatively labeled PCP samples which were not supposed to contain sulfate and sulfonate surfactants. The results demonstrated robustness of the developed nontarget analyzing strategy in identifying and characterizing sulfate and sulfonate surfactants and consequently providing guidance for management and regulation of chemical addition in PCPs to ensure safe use.
研究领域:
环境科学
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分析化学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
·
2026
·
IF 3.4
Ting Yu,Yuan Sun,Fang-Ning Qiu,Ke Liu,Chun-Lu Liu,Qiu-Yi Pu,Hui-Jun Li
Paris species, known as “Chonglou” in traditional Chinese medicine, have been used clinically for millennia. Nevertheless, the variation patterns of their chemical constituents and biological activities among different species are still poorly understood and urgently need to be elucidated. Current research has largely focused on a few pharmacopoeial species, while many with ethnomedicinal value remain scientifically unexplored. This study presents the first integrated metabolomic and pharmacological comparison of two pharmacopoeial species, P. polyphylla Smith var. chinensis (PPC) and P. polyphylla Smith var. yunnanensis (PPY), with two ethnomedicinal species, P. thibetica France (PT) and P. fargesii France (PF). A comprehensive phytochemical profile was established using UPLC-Q-TOF-MS/MS, identifying 119 compounds, 85.7% of which were steroidal saponins. Significant inter-species variation in total saponin content was observed, with PF showing the highest average. Multivariate statistical analysis successfully identified species-specific markers and revealed unexpected chemotaxonomic affinities. Pharmacologically, all four species exhibited significant dual bioactivities. They demonstrated potent hemostatic effects, significantly reducing tail bleeding time and directly inducing platelet aggregation. Concurrently, the extracts showed considerable anti-hepatocarcinoma activity. Mechanistically, this anti-cancer effect involved the induction of S -phase cell cycle arrest and apoptosis, which were associated with down-regulation of Bcl-2 and suppression of c-Myc signaling. The above-mentioned findings confirmed PF and PT as promising complementary resources to the official pharmacopoeial species. This work provides a critical chemical and pharmacological foundation for their quality standardization and potential therapeutic application in hemostasis and liver cancer management.
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DOI
PubMed
高影响因子
CURRENT DRUG METABOLISM
·
2024
·Vol. 25
·期 10
·754-768
·
IF 2.1
Xiaoyun Liu,Dafang Zhong,Chongzhuang Tang,Xiaofeng Xu,Hong Lan,Xingxing Diao
Background BPI-460372 is an orally available, covalent, irreversible small molecule inhibitor of the transcriptional enhanced associate domain (TEAD) 1/3/4, which is currently in clinical development for the treatment of cancers with Hippo pathway alterations. Objectives This study aimed to determine the cytochrome P450 (CYP) phenotyping, metabolic stability, and in vitro and in vivo metabolic profile of BPI-460372. Methods The CYP phenotyping and metabolic stability were assessed by measuring the depletion of substrate. The metabolic profile in hepatocytes and rat and dog plasma was analyzed using ultra-high-performance liquid chromatography combined with Orbitrap tandem mass spectrometry (UHPLC-Orbitrap-HRMS). Results BPI-460372 was mainly metabolized by CYP2D6, CYP3A4, and CYP1A2. BPI-460372 exhibited low clearance in human, monkey, and rat hepatocytes, while moderate clearance in dog and mouse hepatocytes. A total of 10 metabolites were identified in five species of hepatocytes, and no human-unique metabolite was detected. In rat plasma and dog plasma, the primary metabolites were M407 (BPI-460430) and M423 (BPI-460456), respectively. The two metabolites were quantitatively determined in rat and dog plasma in pharmacokinetic and toxicological studies. The major metabolic site was 2-fluoro-acrylamide, and major metabolic pathways in hepatocytes, and rat and dog plasma involved oxidative defluorination, hydration, glutathione (GSH) conjugation, hydrolysis, cysteine conjugation, and N-acetyl cysteine conjugation. β-lyase pathway contributed to the metabolism of BPI-460372 in rats to a certain degree. Conclusion This study elucidated the metabolism of BPI-460372 and provided a basis for pharmacokinetic and toxicological species selection, human pharmacokinetics prediction, and assessment of clinical co-administration limitations and possible metabolic pathways in humans.
研究领域:
药理学
·
药物代谢
·
肿瘤学
·
生物化学
·
临床药理学
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分析化学
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毒理学
·
分子生物学
✓ 已验证
DOI
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
·
2025
·
IF 5.4
Yan Du,Yu-lang Chen,Ying Zhang,Yan-lin Zhao,Zhong Huang,Peng Jin,Shuai Ji,Dao-Quan Tang
Ethnopharmacological relevance Mulberry ( Morus alba L.) leaf is a well-known herbal medicine in China for thousands of years. Mulberry leaf can regulate arachidonic acid (ARA) metabolism disorder in obesity and type 2 diabetes mellitus. However, the active ingredients involved in this process are still unclear. Aim of study To explore the potential active ingredients in mulberry leaf against ARA metabolism disorder. Materials and methods In this research, an efficient method combining affinity ultrafiltration, molecular docking, and network pharmacology was developed and applied to explore cyclooxygenase-2 (COX-2) and 5-lipoxygenase (5-LOX) inhibitors from mulberry leaf. Results A total 17 potential inhibitors were screened by affinity ultrafiltration assay and identified by high resolution mass spectrometry. In addition, 8 bioactive ingredients were obtained after re-evaluated by molecular docking and network pharmacology, and their inhibitory activities on COX-2 and 5-LOX were confirmed by in vitro inhibitory assays. The results of cell experiments showed that the expressions of COX-2 and 5-LOX were significantly suppressed by neochlorogenic acid, rutin, isoquercetin, and (−)-syringaresinol-4-O-glucoside. Conclusion Neochlorogenic acid, rutin, isoquercetin, and (−)-syringaresinol-4-O-glucoside may be the potential material basis of mulberry leaf in the regulation of ARA metabolism of obesity and type 2 diabetes mellitus.
研究领域:
药理学
·
分析化学
·
中药学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）