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Cited by 34Mangiferin and Mango ExtractsRetinal Diseases and TreatmentsNatural Antidiabetic Agents Studies

Mangiferin inhibits cell migration and angiogenesis via PI3K/AKT/mTOR signaling in high glucose‑ and hypoxia‑induced RRCECs

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Shi, Jia, Lv, Hongbin, Tang, Chen, Li, Yujie, Huang, Jing, Zhang, Hong·2021·Molecular Medicine Reports
DOI 10.3892/mmr.2021.12112PMC PMC8097750
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Abstract

Mangiferin is a prominent active component that can be derived from several traditional herbs, including Mangifera indica L., Anemarrhena asphodeloides Bge., and Belamcanda chinensis (L.) DC., which displays antidiabetic properties. Diabetic retinopathy (DR), a serious complication caused by diabetes, is the leading cause of blindness. The present study aimed to evaluate the beneficial effects of mangiferin on high glucose (HG)/hypoxia‑induced rat retinal capillary endothelial cell (RRCEC) angiogenesis, as well as the underlying mechanisms. To establish an in vitro model of DR, RRCECs were exposed to 30 mM glucose and hypoxia. Following treatment with different doses of mangiferin (0.05, 0.1 or 0.2 µM), RRCEC viability, migration and angiogenesis were assessed by performing Cell Counting Kit 8, immunofluorescence, wound healing, Transwell and tube formation assays. Western blotting was conducted to evaluate protein expression levels. Furthermore, LY294002 and IGF‑1, an inhibitor and activator of the PI3K/AKT/mTOR signaling pathway, respectively, were used to verify the potential mechanisms underlying mangiferin. The results demonstrated that mangiferin notably inhibited HG/hypoxia‑induced RRCEC migration and angiogenesis. HG/hypoxia‑induced upregulation of hypoxia‑inducible factor‑1α, vascular endothelial growth factor, matrix metallopeptidase (MMP)2 and MMP9 expression levels and the phosphorylation of PI3K, AKT and mTOR in RRCECs was significantly reversed following treatment with mangiferin. Additionally, further activation of the PI3K/AKT signaling pathway by IGF‑1 inhibited the beneficial effects of mangiferin on RRCECs, whereas deactivation of the PI3K/AKT signaling pathway by LY294002 displayed the opposite results. Collectively, the results of the present study suggested that mangiferin suppressed RRCEC angiogenesis via modulating the PI3K/AKT/mTOR signaling pathway, which could serve as an effective treatment strategy for DR.

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  • MGF crosses the blood-retinal barrier.

    “Notably, the capacity of MGF to cross the blood-retinal barrier enhances its therapeutic efficacy (130).”

    From Mangiferin in human disease: Multifaceted mechanisms and applications (Review) (2026) · cites this paper as [130]

    The Discussion mentions blood-retinal barrier injury caused by hyperglycemia and hypoxia, but does not say mangiferin crosses the barrier. The Methods describe applying mangiferin directly to cultured retinal endothelial cells; they do not test barrier penetration or whether it enhances therapeutic efficacy. Searched for blood-retinal barrier crossing and penetration. (LLM, conf=0.76)

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Cited by

Sorted by citations

Authors
Shi, J., Lv, H., Tang, C., Li, Y., Huang, J., & Zhang, H.
Affiliations
  • Department of Ophthalmology, The People's Hospital of Deyang City, Deyang, Sichuan 618000, P.R. China
  • Southwest Medical University (CN)
Corresponding author
Lv, Hongbin
ORCID
Venue
Molecular Medicine Reports
Publisher
Spandidos Publications
Published
2021-04-21
Volume
23
Issue
6
ISSN
  • 1791-2997 (ISSN-L)
  • 1791-3004
DOI
10.3892/mmr.2021.12112
PMC
PMC8097750
OpenAlex
W3156531642
Cited by
34
References
2
Citations by year
2026: 5 · 2025: 6 · 2024: 6 · 2023: 6 · 2022: 9 · 2021: 2
FWCI
6.48
Type
journal article
Language
en
Open access
Licence
cc-by-nc-nd
Locations
  • Molecular Medicine Reports (publishedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
Funders
Sichuan Province Science and Technology Support Program
Topics
  • Health Sciences › Medicine › Complementary and alternative medicine › Mangiferin and Mango Extracts
  • Health Sciences › Medicine › Ophthalmology › Retinal Diseases and Treatments
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Natural Antidiabetic Agents Studies
Keywords
mangiferin, diabetic retinopathy, retinal microvascular endothelial cells, angiogenesis, cell migration, PI3K/AKT/mTOR pathway, high glucose, hypoxia, hypoxia-inducible factor-1α, vascular endothelial growth factor, MMP-2, MMP-9, insulin-like growth factor I, LY294002
MeSH terms
Animals, Cell Movement, Cells, Cultured, Glucose, Retinal Vessels, Signal Transduction, Cell Hypoxia, Neovascularization, Physiologic, Phosphatidylinositol 3-Kinases, Endothelial Cells, Xanthones, Proto-Oncogene Proteins c-akt, Rats, TOR Serine-Threonine Kinases

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