Absorption, Metabolism, and Pharmacokinetics Profiles of Norathyriol, an Aglycone of Mangiferin, in Rats by HPLC-MS/MS

Cheng, Mingcang; Hu, Pei; Shi, Zhangpeng; Chen, Shuoji; Liu, Huan; Shi, Hao-yun; Xu, Zhou; Tian, Xiaoting; Huang, Chenggang

doi:10.1021/acs.jafc.8b03763

Cited by 15 publications

(7 citation statements)

References 36 publications

(52 reference statements)

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“…Mangiferin can also be excreted directly through phase II reaction. Besides, the study has shown that glucuronidation and sulfation conjugates were found to be the main forms existing in vivo after administration, which is consistent with our experimental results . Norathyriol, the deglycosylation metabolite of mangiferin was responsible for the hypouricaemic effect of mangiferin via inhibiting xanthine oxidase activity .…”

Section: Discussionsupporting

confidence: 90%

Comprehensive Profiling of Mangiferin Metabolites In Vivo and In Vitro Based on the “Drug Metabolite Clusters” Analytical Strategy

et al. 2023

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Mangiferin, a natural flavonoid compound with multiple biological activities (e.g., anti-inflammatory, anti-oxidant, anti-diabetic, and anti-tumor), has gained increased research interest in recent years. Nevertheless, the metabolic processing of mangiferin has not been fully investigated. In this study, a rapid and efficient analytical strategy named “Drug Metabolite Clusters” was applied for comprehensive profiling of mangiferin metabolites in rat plasma, urine, and feces samples in vivo following oral administration and liver microsomes in vitro. First, the biological samples were pretreated with methanol, acetonitrile, and solid phase extraction (SPE) for further liquid chromatography–mass spectrometry (LC–MS) analysis. Second, the raw data were acquired using ultra-high performance liquid chromatography quadrupole exactive orbitrap high-resolution mass spectrometry (UHPLC-Q-Exactive Orbitrap HRMS) under the positive and negative full-scan/dd MS2 modes. Third, mangiferin and its basic metabolites (norathyriol, trihydroxyxanthone, and dihydroxyxanthone) were selected as mangiferin metabolite cluster centers by referring to the relevant literature. Subsequently, according to the pyrolysis law of mass spectrometry, literature reports, and reference material comparison, especially the diagnostic product ions (DPIs), the candidate metabolites were accurately preliminarily identified, and mangiferin metabolite clusters based on metabolite cluster center changes were formed. As a result, a total of 67 mangiferin metabolites (mangiferin included) were detected, including 29 in plasma, 48 in urine, 12 in feces, and 6 in liver microsomes. Among them, trihydroxyxanthones were first detected in rat urine samples after oral mangiferin. We found that mangiferin mainly underwent deglucosylation, dehydroxylation, methylation, glucuronidation, sulfation, and other composite reactions in rats. Herein, we have elucidated the metabolites and metabolic pathways of mangiferin in vivo and in vitro, which provided an essential theoretical basis for further pharmacological studies of mangiferin and a comprehensive research method for the identification of drug metabolites.

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Section: Discussionsupporting

confidence: 90%

Comprehensive Profiling of Mangiferin Metabolites In Vivo and In Vitro Based on the “Drug Metabolite Clusters” Analytical Strategy

et al. 2023

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“…Compound M27 with the retention time at 26.42 min, exhibited deprotonated molecular ion at m/z 401.1240, 48 Da more than that of compound 41 , revealing that they were three hydroxyls bonding metabolites . Compound M28 with the retention times at 40.98 min, exhibited [M‐H] − at m/z 433.0950, 80 Da more than that of compound P29 , revealing that they were sulfate conjugation metabolites . The most abundant signal in secondary fragmentation map was at m/z 353.1383, which implied the neutral loss of 80 Da (SO 3 ) from the parent ion, attesting the compound was readily associated with sulfate conjugation.…”

Section: Resultsmentioning

confidence: 99%

A target‐group‐change couple with mass defect filtering strategy to identify the metabolites of “Dogel ebs” in rats plasma, urine and bile

Dong

et al. 2019

J of Separation Science

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“Dogel ebs” was known as Sophora flavescens Ait., a classical traditional Chinese Mongolian herbal medicine, which had the effects on damp‐heat dysentery, scrofula, and syndrome of accumulated dampness toxicity. Although the chemical constituents have been clarified by our previous studies, the metabolic transformation of “Dogel ebs” in vivo was still unclear. To explore the mechanism of “Dogel ebs,” the metabolites in plasma, bile, and urine samples were investigated. A fast positive and negative ion switching technology was used for the simultaneous determination of flavonoids and alkaloids in “Dogel ebs” in a single run. And a target‐group‐change coupled with mass defect filtering strategy was utilized to analyze the collected data. 89 parent compounds and 82 metabolites were characterized by high‐performance liquid chromatography with quadrupole exactive Orbitrap mass spectrometry. Both phase I and phase II metabolites were observed and the metabolic pathways involved in oxidation, demethylation, acetylation, and glucuronidation. 69 metabolites of “Dogel ebs,” including three hydroxyls bonding xanthohumol, formononetin‐7‐O‐glucuronide, 2′‐hydroxyl‐isoxanthohumol decarboxylation metabolite, oxysophocarpine dehydrogen, 9α‐hydroxysophoramine‐O‐glucuronide, etc. were reported for the first time.

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“…Sugar compounds rhamnose, glucose, and sucrose were detected at m/z 163.0598, 179.0547, and 341.1077, respectively [14,15]. (Figure S8) [31]. m/z 285.0615, 321.0604, and 331.0655 were proposed to be hydroquinone glucuronide, leucodelphinidin, and 3-Glucogallic acid following the comparison with the HMDB database and literatures [15,32].…”

Section: Identification Of Secondary Metabolitesmentioning

confidence: 94%

“…The peak at m/z 191.0548 [M-H] − was supposed as quinic acid by detecting fragmented peaks at m/z 173.0445, 127.0388, 109.0282, and 93.0333 with the loss of H 2 O, CH 4 O 3 , CH 6 O 4 , and CH 6 O 5 , accordingly (Figure S7) [30]. m/z 259.0242 [M-H] − was identified as norathyriol based on fragmentation peaks at m/z 231.0295, 215.0345, 187.0394, and 171.0444 with the loss of CO, CO 2 , C 2 O 3 , and C 2 O 4 (FigureS8)[31]. m/z 285.0615, 321.0604, and 331.0655 were proposed to be hydroquinone glucuronide, leucodelphinidin, and 3-Glucogallic acid following the comparison with the HMDB database and literatures[15,32].m/z 337.0917 showed fragmented ions at m/z 191.0555, 173.0449, and 163.0393 upon fragmentation at collision energy (CE) 10 eV and it was characterized as 3-p-Coumaroylquinic acid[20,33].…”

mentioning

confidence: 99%

Metabolite Profiling of Manilkara zapota L. Leaves by High-Resolution Mass Spectrometry Coupled with ESI and APCI and In Vitro Antioxidant Activity, α-Glucosidase, and Elastase Inhibition Assays

Islam

Alam

Ann

et al. 2020

IJMS

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High-resolution mass spectrometry equipped with electrospray ionization (ESI) and atmospheric pressure chemical ionization (APCI) sources was used to enhance the characterization of phytochemicals of ethanol extracts of Manilkara zapota L. leaves (ZLE). Sugar compounds, dicarboxylic acids, compounds of phenolic acids and flavonoids groups, and other phytochemicals were detected from the leaves. Antioxidant activity and inhibition potentiality of ZLE against α-glucosidase enzyme, and elastase enzyme activities were evaluated in in vitro analysis. ZLE significantly inhibited activities of α-glucosidase enzyme at a lower concentration (IC50 2.51 ± 0.15 µg/mL). Glucose uptake in C2C12 cells was significantly enhanced by 42.13 ± 0.15% following the treatment with ZLE at 30 µg/mL. It also exhibited potential antioxidant activities and elastase enzyme inhibition activity (IC50 27.51 ± 1.70 µg/mL). Atmospheric pressure chemical ionization mass spectrometry (APCI–MS) detected more m/z peaks than electrospray ionization mass spectrometry (ESI–MS), and both ionization techniques illustrated the biological activities of the detected compounds more thoroughly compared to single-mode analysis. Our findings suggest that APCI along with ESI is a potential ionization technique for metabolite profiling, and ZLE has the potential in managing diabetes by inhibiting α-glucosidase activity and enhancing glucose uptake.

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Absorption, Metabolism, and Pharmacokinetics Profiles of Norathyriol, an Aglycone of Mangiferin, in Rats by HPLC-MS/MS

Cited by 15 publications

References 36 publications

Comprehensive Profiling of Mangiferin Metabolites In Vivo and In Vitro Based on the “Drug Metabolite Clusters” Analytical Strategy

Comprehensive Profiling of Mangiferin Metabolites In Vivo and In Vitro Based on the “Drug Metabolite Clusters” Analytical Strategy

A target‐group‐change couple with mass defect filtering strategy to identify the metabolites of “Dogel ebs” in rats plasma, urine and bile

Metabolite Profiling of Manilkara zapota L. Leaves by High-Resolution Mass Spectrometry Coupled with ESI and APCI and In Vitro Antioxidant Activity, α-Glucosidase, and Elastase Inhibition Assays

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