Comprehensive Profiling of Mangiferin Metabolites In Vivo and In Vitro Based on the “Drug Metabolite Clusters” Analytical Strategy
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High Resolution Image Download MS PowerPoint Slide 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 MS 2 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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Metabolic lability and conjugation curtail exposure to the parent compound MGF.
“ii) metabolic lability and conjugation that curtails exposure to the parent compound MGF (21,167,168)”
From Mangiferin in human disease: Multifaceted mechanisms and applications (Review) (2026) · cites this paper as [167]
The Introduction (page not provided) describes mangiferin as having low bioavailability, and the Discussion (page not provided) reports extensive metabolism and conjugates as major forms in vivo. These passages support metabolic lability and conjugation, but do not establish that those processes curtail exposure to the parent compound. (LLM, conf=0.84)
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- Authors
- Zhou, H., Song, S., Lan, X., Li, Y., Yuan, X., Yang, J., Li, M., Cao, T., & Zhang, J.
- Affiliations
- Shandong University of Traditional Chinese Medicine (CN)
- Binzhou Medical University (CN)
- Yuhuangding Hospital (CN)
- Chinese Academy of Sciences (CN)
- Corresponding author
- Li, Min
- Cao, Ting
- Zhang, Jiayu
- Venue
- ACS Omega
- Publisher
- American Chemical Society (ACS)
- Published
- 2023-03-09
- Volume
- 8
- Issue
- 11
- Pages
- 9934-9946
- ISSN
- 2470-1343 (ISSN-L)
- PMC
- PMC10035007
- OpenAlex
- W4323659610
- Cited by
- 15
- References
- 31
- Citations by year
- 2026: 5 · 2025: 4 · 2024: 4 · 2023: 2
- FWCI
- 4.59
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- ACS Omega (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Funders
- Shandong Province (10073004, 2021CXGC010511, TSQN202103110)
- Binzhou Medical University (2019KYQD06)
- Topics
- Health Sciences › Medicine › Complementary and alternative medicine › Mangiferin and Mango Extracts
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Pharmacogenetics and Drug Metabolism
- Health Sciences › Medicine › Complementary and alternative medicine › Traditional Chinese Medicine Analysis
- Keywords
- mangiferin, flavonoid metabolism, rat plasma, urine, feces, liver microsomes, norathyriol, glucuronidation, sulfation, methylation, dehydroxylation, deglucosylation, metabolic pathways
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