Cited by 185Mangiferin and Mango ExtractsChronic Kidney Disease and DiabetesNatural Antidiabetic Agents Studies

Mangiferin attenuates diabetic nephropathy by inhibiting oxidative stress mediated signaling cascade, TNFα related and mitochondrial dependent apoptotic pathways in streptozotocin-induced diabetic rats

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Pal, Pabitra Bikash, Sinha, Krishnendu, Sil, Parames C.·2014·PLoS ONE

Abstract

Oxidative stress plays a crucial role in the progression of diabetic nephropathy in hyperglycemic conditions. It has already been reported that mangiferin, a natural C-glucosyl xanthone and polyhydroxy polyphenol compound protects kidneys from diabetic nephropathy. However, little is known about the mechanism of its beneficial action in this pathophysiology. The present study, therefore, examines the detailed mechanism of the beneficial action of mangiferin on STZ-induced diabetic nephropathy in Wister rats as the working model. A significant increase in plasma glucose level, kidney to body weight ratio, glomerular hypertrophy and hydropic changes as well as enhanced nephrotoxicity related markers (BUN, plasma creatinine, uric acid and urinary albumin) were observed in the experimental animals. Furthermore, increased oxidative stress related parameters, increased ROS production and decreased the intracellular antioxidant defenses were detected in the kidney. Studies on the oxidative stress mediated signaling cascades in diabetic nephropathy demonstrated that PKC isoforms (PKCα, PKCβ and PKCε), MAPKs (p38, JNK and ERK1/2), transcription factor (NF-κB) and TGF-β1 pathways were involved in this pathophysiology. Besides, TNFα was released in this hyperglycemic condition, which in turn activated caspase 8, cleaved Bid to tBid and finally the mitochorndia-dependent apoptotic pathway. In addition, oxidative stress also disturbed the proapoptotic-antiapoptotic (Bax and Bcl-2) balance and activated mitochorndia-dependent apoptosis via caspase 9, caspase 3 and PARP cleavage. Mangiferin treatment, post to hyperglycemia, successfully inhibited all of these changes and protected the cells from apoptotic death.

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Crossref · 10.1371/journal.pone.0107220

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  • MAPK modulation by MGF is context dependent; a number of models show attenuation of ERK1/2, JNK and p38 phosphorylation, reduced AP-1 activity, and consequent decreases in proliferation and cytokine output.

    “MAPK modulation is context dependent; a number of models show attenuation of ERK1/2, JNK and p38 phosphorylation, reduced activator protein (AP)-1 activity, and consequent decreases in proliferation and cytokine output (38,46).”

    From Mangiferin in human disease: Multifaceted mechanisms and applications (Review) (2026) · cites this paper as [46]

    The Results section, “Mangiferin inhibits STZ-induced activation of MAPKs” (page unavailable), reports that mangiferin reversed increased p38, JNK and ERK1/2 phosphorylation in diabetic rat kidney. The Discussion also reports decreased TNFα with treatment, but the paper does not establish reduced AP-1 activity, decreased proliferation, or the claimed sequence linking those effects to MAPK attenuation. (LLM, conf=0.88)

    Experimental — accuracy not yet measured
  • In a STZ-induced diabetic nephropathy rat model, mangiferin markedly decreased plasma glucose, kidney to body weight ratio, BUN, plasma creatinine, uric acid and urinary albumin.

    “They investigated the specific mechanisms underlying the protective effects of mangiferin in a STZ-induced diabetic nephropathy rat model and observed that mangiferin markedly decreased plasma glucose, kidney to body weight ratio, blood urea nitrogen (BUN), plasma creatinine, uric acid and urinary albumin.”
  • Glomerular hypertrophy and hydropsy were attenuated following mangiferin treatment at an oral dose of 40 mg/kg body weight/day in water for 30 days in a STZ-induced DN rat model.

    “Additionally, glomerular hypertrophy and hydropsy was attenuated following mangiferin treatment at an oral dose of 40 mg/kg body weight/day in water for 30 days (34).”
  • Mangiferin protects kidneys from diabetic nephropathy.

    “Surprisingly, Pal et al (34) demonstrated that mangiferin could protect kidneys from DN.”

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Research works printed but not linked: 6

  1. [1]Bonnefont-Rousselot D, Beaudeux JL, Therond P, Peynet J, Legrand A, et al (2004) Diabetes mellitus, oxidative stress and advanced glycation endproducts. Ann Pharm Fr 62: 147– 157. 15243348
  2. [41]Uchida K, Stadtman ER (1993) Covalent attachment of 4-hydroxynonenal to glyceraldehydes-3-phosphate dehydrogenase. J Biol Chem 268: 6388– 6393. 8454610
  3. [46]Ellman GL (1959) Tissue sulphydryl group. Arch Biochem Biophys 82: 70– 77. 13650640
  4. [48]Woessner JF (1961) The determination of hydroxyproline in tissueand protein samples containing small proportions of this iminoacid. Arch Biochem Biophys 93: 440– 447. 13786180
  5. [50]Das J, Sil PC (2012) Taurine ameliorates alloxan-induced diabetic renal injury, oxidative stressrelated signaling pathways and apoptosis in rats. Amino Acids 43: 1509– 23. 22302365
  6. [63]Ha H, Yu MR, Choi YJ, Kitamura M, Lee HB (2002) Role of high glucoseinduced nuclear factor-KB activation in monocyte chemoattractant protein-I expression by mesangial cells. J Am Soc Nephrol 13: 894– 902. 11912248

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Authors
Pal, P. B., Sinha, K., & Sil, P. C.
Affiliations
Bose Institute (IN)
Corresponding author
Sil, Parames C.
Venue
PLoS ONE
Published
2014-09-18
Volume
9
Issue
9
Pages
e107220
ISSN
1932-6203 (ISSN-L)
OpenAlex
W1981550821
Cited by
185
References
74
Citations by year
2026: 6 · 2025: 10 · 2024: 15 · 2023: 14 · 2022: 16 · 2021: 12 · 2020: 18 · 2019: 16 · 2018: 16 · 2017: 24 · 2016: 25 · 2015: 12 · 2014: 1
FWCI
44.44
Type
journal article
Language
en
Open access
Locations
  • PLoS ONE (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • Human Resource Development Group
  • Division of Human Resource Development
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, diabetic nephropathy, oxidative stress, streptozotocin-induced diabetes, TNF-α, mitochondrial apoptosis, caspase activation, NF-κB, MAPK signaling, PKC isoforms, TGF-β1, renal protection, polyphenols
MeSH terms
Animals, Antioxidants, Blood Glucose, Diabetes Mellitus, Experimental, Diabetic Nephropathies, Hydroxyproline, Hyperglycemia, Kidney Glomerulus, Male, Mitochondria, Protein Kinase C, Streptozocin, Tumor Necrosis Factor-alpha, Xanthine Oxidase, Signal Transduction, NF-kappa B, Glycation End Products, Advanced, Rats, Wistar, Apoptosis, Reactive Oxygen Species, Oxidative Stress, Mitogen-Activated Protein Kinases, Xanthones, Apoptosis Regulatory Proteins, Rats, Transforming Growth Factor beta1

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