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JOURNAL OF ETHNOPHARMACOLOGY · 2023 · IF 5.4

Unveiling hepatotoxicity distinction of coumarin-related compounds from glycosides to aglycones in Fructus Psoraleae by integrating UPLC-Q-TOF-MS and high content analysis

Benyu Liu,Shiming Fang,Kun Zhou,Lulu Ma,Yaling Shi,Yuefei Wang,Xiumei Gao

Ethnopharmacological relevance Fructus Psoraleae (FP), the dried and ripe fruit of Cullen corylifolium (L.) Medik., is widely used due to its various clinical pharmacological effects, but its hepatotoxicity restricts its clinical application. So far, its hepatotoxic components and their underlying mechanism have not been systematically elucidated. Aim of the study This study was undertaken to reveal the hepatotoxicity distinction of coumarin-related compounds from glycosides to aglycones in FP and elucidate their potential mechanism. Methods Rats were administrated with the aqueous extract of Fructus Psoraleae (AEFP), in which eight coumarin-related compounds were focused. Subsequently, compounds exposed in rats' livers were detected by UPLC-Q-TOF-MS, and the identified hepatotoxic compounds were evaluated to elaborate their possible mechanism by the aid of high content analysis (HCA). Results Eight coumarin-related compounds were identified, among which psoralenoside (PO), isopsoralenoside (IPO), psoralen (P), and isopsoralen (IP) were the principally exposed compounds in rats' livers. Furocoumarinic acid glucoside (FAG), ( E )-3-(4-(((2 S , 3 R , 4 S , 5 S , 6 R )-3,4,5-trihydroxy-6-(hydroxymethyl) tetrahydro-2 H -pyran-2-yl) oxy) benzofuran-5-yl) acrylic acid (isofurocoumarinic acid glucoside, IFAG), furocoumarinic acid (FA), and ( E )-3-(4-hydroxybenzofuran-5-yl) acrylic acid (isofurocoumarinic acid, IFA) were also detected in low abundance. P, IP, FA, and IFA were identified as the hepatotoxic compounds, while their glycosides were almost non-hepatotoxic. The HCA's results showed that hepatotoxic compounds disrupted the balance in reactive oxygen species (ROS), nuclear area, and mitochondrial membrane potential of HepG2 cells, leading to the occurrence of hepatotoxicity. Conclusions P, IP, FA, and IFA were identified as hepatotoxic compounds, from which P and IP were proposed as the important risk components for hepatotoxicity. The conversion from glycosides to aglycones played an essential role in FP-induced hepatotoxicity.

CAS / MDL: 64-18-6
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FOOD CONTROL · 2022 · IF 6.652

Structural annotation and discovery of toxic cyclopeptides and their analogues in lethal mushroom Amanita and Lepiota species using UPLC-HRMS and molecular networking strategy

Zhiyong Zhao,Hengchao E,Enjing Tian,Tingting Fan,Xianli Yang,Xiaobei Li,Yanmei Zhang,Xujiao Li,Ailiang Chen,Changyan Zhou,Xiaoyan Zhao

Foodborne poisoning caused by the cyclopeptide toxins-producing mushroom species seriously endangers human life health. In recent years discovery of new cyclopeptides is getting more attention not only for their toxicity but also for their specific bioactivity. In this study, a combined strategy using liquid chromatography tandem high resolution mass spectrometry and the feature-based molecular networking analysis was established to identify the known cyclopeptide toxins and discover new cyclopeptides in the cyclopeptide toxins-producing mushroom species. The specific fragmentation behaviors of the known cyclopeptide toxins were systematically annotated. Four new phallotoxin analogues were identified for the first time, the chemical structures of which were completely deduced. Moreover, the chemical profiles of the toxic cyclopeptides in lethal mushroom Amanita and Lepiota species were investigated by the self-built cyclopeptides database. The developed strategy could be utilized as a useful tool for identifying the cyclopeptide toxins-induced food poisoning , as well as aid in the discovery of more unknown cyclopeptides.

CAS / MDL: 540-69-2 7647-01-0
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MICROCHEMICAL JOURNAL · 2023 · IF 4.8

Analytical quality by design oriented development of the UPLC method for analysing multiple pharmaceutical process intermediates: A case study of Compound Danshen Dripping Pills

Yanni Tai,Dandan Ren,Wanshun Zhao,Haibin Qu,Haoshu Xiong,Xingchu Gong

This work presented the integration of the Analytical Quality by Design concept in developing a UPLC method for the quantification of saponins and phenolic acids in two Compound Danshen Dripping Pills intermediates of a concentrated extract and a supernatant. Prior knowledge and systematic risk analysis were conducted to identify potential critical method parameters (CMPs) that affected critical quality attributes (CQAs). A definitive screening design was employed to investigate the quantitative relationship among the intermediate type, CPPs, and CQAs. Intermediate type was added in the experimental design table as a categorical variable. After the models were built, the method operable design region (MODR) was calculated with an exhaustive search-Monte Carlo method. The CPP combinations with a 95 % or higher probability of reaching the preset standard were collected in MODR. The MODR robustness test was conducted with a Plackett–Burman design. The separation of analytes was achieved with a Waters Acquity HSS T3 (100 × 2.1 mm, 1.8 µm) column at 30 °C, using 0.05 % phosphoric acid and acetonitrile as the mobile phases in gradient elution at a flow rate of 0.40 mL/min. The elution was monitored at UV detection wavelengths of 280 nm and 203 nm. The optimized method was also validated. Good robustness, accuracy, precision, stability and repeatability, and linear regression (R > 0.9997) were obtained. All recoveries of the 9 compounds ranged from 97.8 % to 101.7 %, with an RSD of less than 3.49 %. Nine batches of Danshensu, protocatechualdehyde, rosmarinic acid, salvianolic acid B, salvianolic acid A, notoginsenoside R 1 , ginsenoside Rg 1 , ginsenoside Re, and ginsenoside Rb 1 were analysed. Danshensu was found to be the compound with the highest content.

CAS / MDL: 7664-38-2
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ENVIRONMENTAL SCIENCE AND POLLUTION RESEARCH · 2022 ·Vol. 30 ·期 10 ·27357-27371 · IF 5.19

Simultaneous trace determination of three natural estrogens and their sulfate and glucuronide conjugates in municipal waste and river water samples with UPLC-MS/MS

Ma Qing-guang,Wan Yi-ping,Liu Ze-hua,Dang Zhi

Analytical method for three natural estrogens (NEs) and their sulfate and glucuronide conjugates in waste and river waters using solid-phase extraction (SPE) coupled with ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) has been available, but problems including poor recovery exist. In order to solve these, some optimizations have been performed in this work. For sample preparation, both rinse and elution solutions were optimized, in which 6 mL of MeOH/water (1:9, v/v), MeOH/Ace/water (10:2:88, v/v/v), and MeOH/NH 4 OH/water (10:2:88, v/v/v) were determined as the rinse solution, while 6 mL of 2.0% NH 4 OH/MeOH was determined as the elution solution for conjugated NEs (C-NEs). For mobile phase, addition of NH 4 F could obviously enhance the signal response of the nine target compounds, and the optimized addition concentration was 0.5 mmol/L. The developed efficient method was validated and showed excellent linearity for each target compound ( R 2  > 0.998), low limit of quantifications (LOQs, 0.07–1.29 ng/L) in four different water matrices, and excellent recovery efficiencies of 81.0–116.1% in influent, effluent, ultra-pure, and river water samples with low relative standard deviations (RSDs, 0.6–13.6%). The optimized method was successfully applied to influent, effluent, and Pearl River water, among which three NEs were all detected, while five C-NEs were found in the influent, three C-NEs were detected in the effluent, and two C-NEs were found in the Pearl River water, indicating the wide distribution of NEs and C-NEs in different water environments. This work provided a reliable and efficient analytical method for simultaneous trace determination of NEs and C-NEs, which had satisfactory absolute recoveries with low RSDs, low LOQs, and time-saving for both analysis and nitrogen drying.

CAS / MDL: 64-19-7
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MICROCHEMICAL JOURNAL · 2026 · IF 5.2

A three-tier screening strategy-based targeted UPLC-ESI-MS/MS platform delineates the FAHFA landscape in lipid extracts of fruit seeds and pits

Long Xu,Xiang Liang,Mengqing Xiao,Walter Vetter,Shuaishuai Yang,Kai Chen,Fashan Wei,Xiaoling Yu,Xia Shen,Mingjiang Zhu

A 3-tier screening strategy-based LC-MS/MS profiles FAHFAs in fruit seeds and pits. • Fruit seed oils contain significantly higher total FAHFA levels than pit oils. • Bayberry seed oil is the richest FAHFA source (168 ng/g) among all samples. • OAHOA and PAHOA are identified as predominant FAHFA species in fruit seeds. Fatty acid esters of hydroxy fatty acids (FAHFAs) are bioactive lipids with anti-inflammatory and antidiabetic properties, but their occurrence in fruit seeds and pits remain largely unexplored. Here, untargeted lipidomics and fatty acid profiling were firstly employed to characterize the overall lipid landscape and precursor pools. Subsequently, a targeted platform was established by integrating solid-phase extraction (SPE) enrichment, N , N -dimethylethylenediamine (DMED) derivatization, and UPLC-ESI-MS/MS in multiple reaction monitoring (MRM) mode. Using a predictive MRM database covering 2116 theoretical FAHFA species and a three-tier screening strategy (two MRM filtering rounds followed by retention time and signal-to-noise evaluation), 49 endogenous species were identified in 17 fruit seeds and 4 fruit pits. It was found that fruit seed oils contained significantly higher total FAHFA levels than pit oils (3–168 vs. 1–35 ng/g), with bayberry seed oil showing the highest content (168 ng/g). Predominant species included OAHOA, LAHLA, PAHOA, and OAHSA. This first comprehensive FAHFA profile, achieved via the three-tier strategy, establishes seed oils as notable dietary sources of these lipids and offers a robust platform for discovering bioactive lipids in complex plant matrices. Download: Download high-res image (113KB) Download: Download full-size image

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FOOD CHEMISTRY · 2021 · IF 7.514

Identification of volatile sulfur-containing compounds and the precursor of dimethyl sulfide in cold-pressed rapeseed oil by GC–SCD and UPLC–MS/MS

Pei Yu,Yini Yang,Jinyuan Sun,Xiao Jia,Chang Zheng,Qi Zhou,Fenghong Huang

Volatile sulfur-containing compounds (VSCs) provide an important contribution to foods due to their special odors. In this study, VSCs in 21 cold-pressed rapeseed oils (CROs) from 9 regions in China were extracted and separated by headspace solid-phase microextraction combined with gas chromatography coupled with sulfur chemiluminescence detection. 19 VSCs were identified by authentic standards, and the total concentration of VSCs in all CROs ranged from 49.0 to 18129 μg/kg. Dimethyl sulfide (DMS), with its high odor activity value (7–14574), was the most significant aroma contributor to the CROs. Furthermore, S-methylmethionine (SMM) in rapeseed was first affirmed by ultra-performance liquid chromatography–tandem mass spectrometry and isotope quantitation. The positive correlation coefficient between DMS and SMM was 0.793 ( p  < 0.05), which confirmed SMM as a crucial precursor of DMS in CROs. This study provided a theoretical basis for selecting rapeseed materials by the distribution of essential VSCs and the source of DMS.

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INTERNATIONAL JOURNAL OF FOOD SCIENCE AND TECHNOLOGY · 2020 ·Vol. 56 ·期 6 ·2983-2991 · IF 2.773

Comparative evaluation of four free radical scavengers for the inhibition of individual glycidyl ester formation in rice bran oil determined by UPLC-MS/MS

Shujie Wang,Guoqin Liu,Weiwei Cheng

Summary This research investigated the effect of carnosic acid (CA), tert-butyl hydroquinone (TBHQ), sesamol (SL) and L-ascorbyl palmitate (AP) on the inhibition of glycidyl esters (GEs) and oxidation parameter changes in rice bran oil (RBO) during heat processing. The electron spin resonance (ESR) analysis showed that the free radical scavenging ability of them was ranked as CA > TBHQ > SL > AP. With the addition of CA, TBHQ, SL and AP (0.6 g kg −1 ), the GEs content was reduced significantly from 987.98 ± 8.45 to 283.87 ± 4.78, 303.21 ± 4.38, 440.52 ± 3.82 and 500.55 ± 2.99 μg kg −1 , respectively. All four free radical scavengers had the highest inhibitory effect on C18:2-GE, followed by C18:1-GE and C16:0-GE. Moreover, the free radical scavengers were also effective to inhibit oil oxidation. Overall, the natural-free radical scavenger may be a promising candidate to mitigate GE formation and oil oxidation due to its effectiveness and safety.

CAS / MDL: 137-66-6 1948-33-0
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BIOMEDICAL CHROMATOGRAPHY · 2020 ·Vol. 34 ·期 10 ·e4919 · IF 1.728

Systematic screening and characterization of absorbed constituents and in vivo metabolites in rats after oral administration of Rhizoma coptidis using UPLC-Q-TOF/MS

Xinchi Feng,Kun Wang,Xintong Hu,Liwei Chai,Shijie Cao,Liqin Ding,Feng Qiu

Rhizoma coptidis has been used for a long time in China owing to its anti-bacterial, anti-diabetes, anti-hyperlipidemia and anti-obesity activities. However, the in vivo biotransformation of Rhizoma coptidis is still unclear to date. In this study, a three-step strategy using UPLC-Q-TOF/MS was applied to clarify the in vivo absorbed constituents and metabolites in rats after oral administration of Rhizoma coptidis. First, alkaloids in Rhizoma coptidis extract were identified. Second, six abundant alkaloids (berberine, palmatine, coptisine, epiberberine, jatrorrhizine, and columbamine) were selected as representative prototypes and the metabolic fates of them in rats were investigated to obtain a database of Rhizoma coptidis -derived metabolites. Finally, the metabolic profiles of Rhizoma coptidis were fully elucidated based on the above-mentioned results. In summary, 29 alkaloids were identified in Rhizoma coptidis , and a database of Rhizoma coptidis -derived metabolites was obtained with 144 characterized metabolites. A total of 89 xenobiotics including 12 absorbed constituents and 77 metabolites were identified in dosed rat biosamples. Major metabolic pathways of Rhizoma coptidis were hydroxylation, reduction, methylation, demethylation, demethylenation, desaturation, glucuronidation and sulfation. This is the first systematic study on the in vivo absorbed constituents and metabolic profiling of Rhizoma coptidis and will be beneficial for its further studies.

CAS / MDL: 10605-02-4
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Food & Function · 2019 ·Vol. 10 ·期 9 ·5656-5668 · IF 3.241

Urinary and plasmatic metabolomics strategy to explore the holistic mechanism of lignans in S. chinensis in treating Alzheimer's disease using UPLC-Q-TOF-MS

Mengying Wei,Zhongying Liu,Yuanyuan Liu,Shizhe Li,Mingxin Hu,Kexin Yue,Tianshu Liu,Yang He,Zifeng Pi,Zhiqiang Liu,Fengrui Song

Schisandra chinensis (Turcz.) Baill (S. chinensis), a functional food, is used as a tonic and sedative agent in traditional Chinese medicine. Modern pharmacological research has proved that S. chinensis could prevent and treat age-related neurodegenerative diseases. The presence of bioactive lignans in S. chinensis is the main reason for its neuroprotective and cognitive enhancement effects. This study aimed to clarify the mechanism of lignans in S. chinensis in ameliorating learning and memory deficits in Alzheimer's disease (AD) animals. The step-down test and Morris water maze (MWM) test were used to verify the effects of lignans in S. chinensis on learning and memory in AD animals. Then, metabolomics approaches based on ultraperformance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS) were used to clarify the mechanism of lignans in S. chinensis in treating AD. Finally, quantitative analysis of AD-related neurotransmitters in the brain was conducted after treatment with lignans in S. chinensis. In the MWM and step-down tests, lignans in S. chinensis showed a clear ability to ameliorate the impaired learning and memory of AD animals. A total of 31 endogenous metabolites were identified after treatment with lignans in S. chinensis, which were associated with lignans ameliorating learning and memory. These biomarkers were mainly associated with polyunsaturated fatty acid metabolism and amino acid and vitamin metabolism. Moreover, lignans in S. chinensis upregulated the levels of γ-aminobutyric acid (GABA), 5-hydroxytryptamine (5-HT), acetylcholine (Ach), norepinephrine (NE) and glycine (Gly) and downregulate the level of aspartic acid (Asp). Lignans in S. chinensis might alleviate the neurotoxic effects of neurological inflammation and oxidative stress, Aβ deposition, and tau phosphorylation via the regulation of multiple endogenous metabolic pathways during pathological AD. The research might provide useful support for the further study of pharmacology and new drug development of lignans in S. chinensis.

CAS / MDL: 506-32-1 63-91-2
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Evidence-based Complementary and Alternative Medicine · 2019 · IF 1.984

Identification and Analysis of Chemical Constituents and Rat Serum Metabolites in Lycopodium clavatum Using UPLC-Q-TOF/MS Combined with Multiple Data-Processing Approaches

Xin Li,Mingqin Kang,Ningning Ma,Tan Pang,Yanjun Zhang,Hua Jin,Zhen Yang,Lili Song

Lycopodium clavatum is a dry whole grass of Lycopodium japonicum Thunb.; it has been extensively used to anti-inflammatory, antioxidant, and antimicrobial actions and inhibits acetylcholinesterase activity. However, it lacks further compounds research of Lycopodium clavatum in vivo and in vitro. In this work, a rapid method was established using the ultra high performance liquid chromatography with quadrupole-time-of-flight mass spectrometry (UPLC-Q-TOF/MS) combined with multiple data-processing approaches for compounds analysis of Lycopodium clavatum in vitro and in vivo. Finally, 30 peaks were characterized in 75% ethanol extract of Lycopodium clavatum and 17 peaks were characterized in rat plasma that including 12 prototype compounds and 5 metabolites. Methylation and demethylation are the main transformation reactions of Lycopodium clavatum in rat serum. This work could be helpful for understanding the complex compounds of Lycopodium clavatum and further analyzing the pharmacological studies of active compounds.

CAS / MDL: 64-18-6
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Food & Function · 2019 ·Vol. 10 ·期 12 ·8042-8055 · IF 3.241

Identifying mechanisms underlying the amelioration effect of Chrysanthemum morifolium Ramat. ‘Boju’ extract on hyperuricemia using biochemical characterization and UPLC-ESI-QTOF/MS-based metabolomics

An Peng,Lianzhu Lin,Mouming Zhao,Baoguo Sun

This study was aimed at evaluating the prospect of edible chrysanthemum extract as a potential substance for the prevention and treatment of hyperuricemia. Chrysanthemum morifolium Ramat. ‘Boju’ extract (CBE), which had the strongest xanthine oxidase inhibitory activity, showed a significant hypouricemic effect on potassium oxonate-induced hyperuricemic rats through inhibiting serum xanthine oxidase activity, regulating renal uric acid transport-related protein (ABCG2, URAT1 and GLUT9) expression and blood lipid levels, and protecting renal function. Serum metabolomics based on UPLC-ESI-QTOF/MS was used to illustrate mechanisms underlying the amelioration effect of CBE on hyperuricemia. A total of 35 potential biomarkers were identified. CBE prevented the pathological process of hyperuricemia by regulating 16/17 biomarkers associated with tryptophan, sphingolipid, glycerophospholipid and arachidonic acid metabolisms. CBE could alleviate hyperuricemia-related diseases including chronic kidney disease, hyperlipidemia and inflammation via reducing indoxyl sulfate, lysophosphatidylcholines and arachidonic acid levels, exhibiting its applicability and superiority in the treatment of hyperuricemia.

CAS / MDL: 64-18-6
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INDUSTRIAL CROPS AND PRODUCTS · 2016 · IF 3.449

Antihyperglycemic, antioxidant activities of two Acer palmatum cultivars, and identification of phenolics profile by UPLC-QTOF-MS/MS: New natural sources of functional constituents

Lu Zhang,Zong-cai Tu,Xing Xie,Yu Lu,Zhen-xing Wang,Hui Wang,Xiao-mei Sha

This research aimed to compare the antihyperglycemic and antioxidant abilities, and to characterize the bioactive constituents of two Acer palmatum cultivars, Acer palmatum ‘ Atropurpureum ’ (APA) and Acer palmatum Thunb (APT). Dry materials were respectively extracted with 70% and 90% methanol, followed by sequentially fractionation with ethyl acetate and n -butanol. The phytochemical profile of selected fraction was determined by using UPLC-QTOF-MS/MS. APT is a better source of natural antioxidants and α- glucosidase inhibitors than APA due to its higher total phenolic content (TPC), and stronger antioxidant and α- glucosidase inhibitory activities. The highest total phenolic and total flavonoid content were found in the ethyl acetate fraction (EAF) of 90% methanol extract of APT (468.49   mg GAE/g Extract) and 70% methanol extract of APA (142.60   mg QuE/g Extract), respectively. The EAF of 70% methanol extract of APT gave the strongest DPPH· scavenging ability, ABTS + · scavenging ability and α- glucosidase inhibitory, with the IC 50 values of 7.06, 4.18 and 1.99   μg/mL, respectively. The latter two were much higher than that of individual positive control. HPLC analysis revealed similar phytochemical profiles of all EAFs. Twenty-five compounds, including 3 organic acids, 5 phenolic acids, 8 tannins, 7 flavonoids and 2 proanthocyanidins, were identified or tentatively identified from APT, with tannins and flavonoid glucosides as the major active compounds. The results indicated a strong potential of Acer palmatum as a natural source of excellent antioxidants and antihyperglycemic compounds in the prevention and treatment of type II diabetes and its complication.

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