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Cited by 7Mangiferin and Mango ExtractsPhytochemicals and Antioxidant ActivitiesDrug Solubulity and Delivery Systems

Human Pharmacokinetic Profiling and Comparative Analysis of Mangiferin and Its Monosodium Derivative from Mangifera indica Extracts Using UHPLC-MS/MS with 1H NMR and MALDI-TOF Confirmation

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Fuentes-Rios, David, Sanchez-Rodriguez, Alvaro, Lopez-Rios, Laura, Garcia-Gonzalez, Eduardo, Martinez-Canton, Miriam, Galvan-Alvarez, Victor, Gallego-Selles, Angel, Martin-Rincon, Marcos +2 more·2025·Molecules
DOI 10.3390/molecules30030461PMC PMC11820055
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Abstract

Mangiferin, a glucosyl xanthone, is a plant metabolite with promising nootropic and ergogenic properties. However, its poor and inconsistent systemic bioavailability limits its therapeutic potential. Additionally, the pharmacokinetics of mangiferin from mango leaf extract formulations remain uncharacterized in humans. This study validated a UHPLC-MS/MS method and conducted a human pharmacokinetic study approved by an ethics committee. The bioavailability of mangiferin and its monosodium salt was assessed from two standardized mango leaf extracts: MLE60, standardized to 60% mangiferin but practically insoluble in water, and MLES, the water-soluble monosodium salt form, also standardized to 60%. Twelve participants (six females) received oral doses of each extract in a crossover design with a 7-day washout period. Plasma analysis showed significantly higher AUC and Cmax values with MLES than MLE60, while Tmax and T1/2 were similar. MLES demonstrated a 2.44-fold increase in AUC0–24h compared to MLE60 (p = 0.0029 **), indicating improved bioavailability. This study highlights the salification method as a simple strategy to enhance mangiferin bioavailability, enabling broader applications in beverages and other products where solubility is a limitation.

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  • Low solubility and permeability constrain Cmax/AUC after oral dosing.

    “i) Low solubility and permeability [constraining Cmax/area under the curve (AUC) after oral dosing] ((164-166)”

    From Mangiferin in human disease: Multifaceted mechanisms and applications (Review) (2026) · cites this paper as [166]

    The Results (Section 2.3) report higher Cmax and AUC after oral dosing of the water-soluble mangiferin formulation than the poorly soluble one. However, the Discussion and Conclusions describe diminished permeability as a likely or hypothesized mechanism, not an established cause of the measured Cmax and AUC differences. (LLM, conf=0.85)

    Experimental — accuracy not yet measured

  • Nanodelivery research consistently shows improvements in MGF solubility, uptake, and systemic exposure.

    “This approach is justified by consistent improvements in solubility, uptake and systemic exposure demonstrated in nanodelivery research, as well as by early human PK findings that MGF monosodium salt substantially increases bioavailability compared with the parent compound (166,195).”

    From Mangiferin in human disease: Multifaceted mechanisms and applications (Review) (2026) · cites this paper as [166]

    The Introduction lists formulation approaches, including lipid emulsions and lipo- or phytosomes, as strategies used to improve mangiferin bioavailability. It does not establish that nanodelivery research consistently improves all three claimed outcomes: solubility, uptake, and systemic exposure. The paper's own human pharmacokinetic result concerns a monosodium salt, not a nanodelivery formulation (Results, §2.3). (LLM, conf=0.83)

    Experimental — accuracy not yet measured

  • Early human data on MGF are limited, heterogeneous, and not definitive for purified MGF.

    “Early human data are limited, heterogeneous (often extract-based) and not yet definitive for purified MGF.”

    From Mangiferin in human disease: Multifaceted mechanisms and applications (Review) (2026) · cites this paper as [166]

  • Early human PK findings show MGF monosodium salt substantially increases bioavailability compared with the parent compound.

    “This approach is justified by consistent improvements in solubility, uptake and systemic exposure demonstrated in nanodelivery research, as well as by early human PK findings that MGF monosodium salt substantially increases bioavailability compared with the parent compound (166,195).”

    From Mangiferin in human disease: Multifaceted mechanisms and applications (Review) (2026) · cites this paper as [166]

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References 41 · Cited by 7

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Authors
Fuentes-Rios, D., Sanchez-Rodriguez, A., Lopez-Rios, L., Garcia-Gonzalez, E., Martinez-Canton, M., Galvan-Alvarez, V., Gallego-Selles, A., Martin-Rincon, M., Calbet, J. A. L., & Vega-Morales, T.
Affiliations
  • Nektium Pharma SL, C/Las Mimosas 8, Polígono Industrial Arinaga, 35118 Las Palmas, Spain
  • Department of Physical Education and Research Institute of Biomedical and Health Sciences (IUIBS), University of Las Palmas de Gran Canaria, Campus Universitario de Tafira s/n, 35017 Las Palmas de Gran Canaria, Spain
ORCID
Venue
Molecules
Publisher
MDPI AG
Published
2025-01-21
Volume
30
Issue
3
Pages
461
ISSN
1420-3049 (ISSN-L)
DOI
10.3390/molecules30030461
PMC
PMC11820055
OpenAlex
W4406664808
Cited by
7
References
41
Citations by year
2026: 3 · 2025: 4
FWCI
8.63
Type
journal article
Language
en
Open access
Licence
Locations
  • Molecules (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • University of Las Palmas de Gran Canaria, Nektium Pharma S.L., and Ministerio de Economía y Competitividad (PID2021-125354OB-C21)
  • Consejería de Economía, Conocimiento y Empleo (PID2021-125354OB-C21)
  • European Social Fund (PID2021-125354OB-C21)
Topics
  • Health Sciences › Medicine › Complementary and alternative medicine › Mangiferin and Mango Extracts
  • Health Sciences › Medicine › Biochemistry › Phytochemicals and Antioxidant Activities
  • Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Drug Solubulity and Delivery Systems
Keywords
mangiferin, mango, mango leaf extract, human pharmacokinetics, bioavailability, salification, xanthones, plasma concentration, UHPLC-MS/MS method validation
MeSH terms
Adult, Biological Availability, Chromatography, High Pressure Liquid, Female, Humans, Male, Plant Extracts, Cross-Over Studies, Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization, Mangifera, Xanthones, Tandem Mass Spectrometry, Young Adult, Proton Magnetic Resonance Spectroscopy

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