Drug metabolite cluster centers-based strategy for comprehensive profiling of Neomangiferin metabolites in vivo and in vitro and network pharmacology study on anti-inflammatory mechanism

Lan, Xianming; Li, Yanan; Li, Haoran; Song, Shuyi; Yuan, Xiaoqing; Zhou, Hongyan; Chen, Qimei; Zhang, Jiayu

doi:10.1016/j.arabjc.2022.104268

Cited by 2 publications

(3 citation statements)

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Section: Resultsmentioning

confidence: 99%

“…Consequently, our team first proposed the “Drug Metabolite Clusters” analytical strategy to search for drug metabolites. , The prototype drug generated primary metabolites through drug metabolic enzymes according to certain metabolic rules and then formed primary metabolite cluster centers. The primary metabolites were further metabolized according to the corresponding reactions to form secondary metabolite cluster centers, and finally, Drug Metabolite Clusters was formed.…”

Section: Introductionmentioning

confidence: 99%

“…Furthermore, the dominant fragment ion at m/z 187 also appeared in its ESI-MS/MS spectrum. Combined with the literature,22,25 M15 was identified as norathyriol, which was thought to possess various pharmacological activities. M37, M41, and M42 produced their [M-H] − ions at m/z 273.03903, m/z 273.04001, and m/z 273.03976 (C 14 H 9 O 6 , mass errors of −3.887, 2.364, and 1.449 ppm), which were eluted at 12.51, 13.44, and 14.70 min, respectively.…”

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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: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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