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Cited by 67Mangiferin and Mango ExtractsChronic Kidney Disease and DiabetesNatural Antidiabetic Agents Studies

Mangiferin Alleviates Renal Interstitial Fibrosis in Streptozotocin-Induced Diabetic Mice through Regulating the PTEN/PI3K/Akt Signaling Pathway

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Song, Yanyan, Liu, Wei, Tang, Ke, Zang, Junting, Li, Dong, Gao, Hang·2020·Journal of Diabetes Research
DOI 10.1155/2020/9481720PMC PMC7016412
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Abstract

Renal interstitial fibrosis is considered to be the typical manifestation of diabetic nephropathy (DN). Mangiferin has shown positive effect on the prevention or treatment of diabetes and its complications. The aim of this study was to explore the inhibitive effect and mechanism of mangiferin on renal interstitial fibrosis in diabetic mice. Streptozotocin- (STZ-) induced diabetic mice were treated with mangiferin (15, 30, and 60 mg/kg/d) for 4 weeks. The morphology of kidneys was observed by Masson’s trichrome staining, and the biochemical parameters (fasting blood glucose (FBG), triglyceride (TG), total cholesterol (TC), blood urea nitrogen (BUN), serum creatinine (SCr), and urine protein) were determined by kits. In addition, the levels of inflammatory cytokines (tumor necrosis factor-α (TNF-α), interleukin- (IL-) 6, and IL-1 β), antioxidant enzymes (SOD, CAT, and GSH-Px), MDA, and ROS were assessed. Furthermore, the expressions of fibronectin (FN), collagen I (Col I), and α-SMA were measured by immunohistochemistry. Regulations of TGF-β 1 and the PTEN/PI3K/Akt pathway were detected by Western blotting. Treatment with mangiferin significantly ameliorated renal dysfunction in diabetic mice, as evidenced by the increase in body weight and decreases in FBG, TG, TC, BUN, SCr, urine protein, and the kidney to body weight ratio (KW/BW). Furthermore, mangiferin treatment prevented renal interstitial fibrosis evidenced by decreases in the positive expression of FN, Col I, and α-SMA, in comparison with morphological changes in the renal tissue. Meanwhile, mangiferin increased antioxidant enzymes, reduced the TNF-α, IL-6, and IL-1 β, as well as MDA and ROS. Additionally, mangiferin administration also downregulated TGF-β 1, upregulated PTEN, and decreased the phosphorylation of both PI3K and Akt. These findings demonstrate that mangiferin may reduce inflammation and oxidative stress in DN, thereby inhibiting the renal interstitial fibrosis by reducing the TGF-β 1-mediated elevation of Col I, FN, and α-SMA through the PTEN/PI3K/Akt pathway.

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  • In streptozotocin-induced diabetic mice, oral administration of 15-60 mg/kg/day MGF for 4 weeks may attenuate renal injury, consistent with diabetic nephropathy.

    “In streptozotocin-induced diabetic mice, oral administration of 15-60 mg/kg/day MGF for 4 weeks may attenuate renal injury, which is consistent with diabetic nephropathy.”

    From Mangiferin in human disease: Multifaceted mechanisms and applications (Review) (2026) · cites this paper as [34]

  • In diabetic nephropathy, MGF downregulates PTEN/PI3K/Akt signaling and reduces expression of fibronectin, collagen I and α-SMA, along with decreases in renal fibrosis, inflammation and oxidative stress endpoints.

    “This previous study reported downregulation of phosphatase and tensin homolog (PTEN)/PI3K/Akt signaling, and reduced expression of fibronectin, collagen I and α-smooth muscle actin (α-SMA), along with decreases in renal fibrosis, inflammation and oxidative stress endpoints (34).”

    From Mangiferin in human disease: Multifaceted mechanisms and applications (Review) (2026) · cites this paper as [34]

  • In streptozotocin-induced diabetic mice, MGF (15, 30, or 60 mg/kg) suppresses inflammation and oxidative stress by modulating the PTEN/PI3K/Akt pathway, reducing expression of collagen I, fibronectin, and α-SMA.

    “In streptozotocin-induced diabetic mice, MGF (15, 30 or 60 mg/kg) suppresses inflammation and oxidative stress by modulating the PTEN/PI3K/Akt pathway, leading to reduced expression of fibrotic markers such as collagen I, fibronectin and α-SMA (34).”

    From Mangiferin in human disease: Multifaceted mechanisms and applications (Review) (2026) · cites this paper as [34]

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Cited by

Sorted by citations

Authors
Song, Y., Liu, W., Tang, K., Zang, J., Li, D., & Gao, H.
Affiliations
  • Jilin University (CN)
  • First Hospital of Jilin University (CN)
Corresponding author
  • Li, Dong
  • Gao, Hang
ORCID
Venue
Journal of Diabetes Research
Publisher
Wiley
Published
2020-02-01
Volume
2020
Pages
1-12
ISSN
  • 2314-6745 (ISSN-L)
  • 2314-6753
DOI
10.1155/2020/9481720
PMC
PMC7016412
OpenAlex
W3003266517
Cited by
67
References
2
Citations by year
2026: 3 · 2025: 9 · 2024: 9 · 2023: 12 · 2022: 12 · 2021: 12 · 2020: 10
FWCI
12.74
Type
journal article
Language
en
Open access
Licence
Locations
  • Journal of Diabetes Research (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • Science and Technology Planning Project of Jilin Province (20190701011GH, 81802077)
  • National Natural Science Foundation of China (20190701011GH, 81802077)
Topics
  • Health Sciences › Medicine › Complementary and alternative medicine › Mangiferin and Mango Extracts
  • Health Sciences › Medicine › Nephrology › Chronic Kidney Disease and Diabetes
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Natural Antidiabetic Agents Studies
Keywords
mangiferin, tubulointerstitial fibrosis, diabetic nephropathy, PTEN/PI3K/AKT signaling pathway, TGF-β1, oxidative stress, renal inflammation, type I collagen, fibronectin, alpha-smooth muscle actin, streptozotocin-induced diabetes, antioxidant enzymes, renal protection, proteinuria, TNF-α, interleukin-6, IL-1β, malondialdehyde, reactive oxygen species
MeSH terms
Actins, Animals, Blood Glucose, Blood Urea Nitrogen, Catalase, Cholesterol, Creatinine, Diabetes Mellitus, Experimental, Diabetic Nephropathies, Fibronectins, Fibrosis, Glutathione Peroxidase, Kidney, Malondialdehyde, Superoxide Dismutase, Triglycerides, Tumor Necrosis Factor-alpha, Signal Transduction, Interleukin-6, Cytokines, Reactive Oxygen Species, Phosphatidylinositol 3-Kinases, Collagen Type I, Xanthones, Proto-Oncogene Proteins c-akt, PTEN Phosphohydrolase, Mice, Interleukin-1beta, Transforming Growth Factor beta1

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