Abstract
Diabetic nephropathy (DN) is one of the notorious diabetes associated complications. Despite many therapeutic strategies available, metabolic control of DN continues to poses a challenge. In this study, the interactions of mangiferin with selected oral hypoglycemic drugs, metformin and gliclazide to effectively alleviate the symptoms of renal injury in DN are evaluated. Male Sprague Dawley rats were used as experimental model and type II diabetes was induced by administration of high fat diet and low dose streptozotocin. Oral intervention of mangiferin with metformin and gliclazide for a period of 28 days was given to diabetic rats. At the end of the treatment period, biochemical parameters, kidney function markers, anti-oxidant enzymes levels, oxidative stress mediated gene expression and histology were analysed. Significant reduction in the serum biochemical markers (glucose, urea and creatinine) were observed in the groups treated with combination drugs. Marked improvement in the combination treated groups in terms of inflammation and oxidative damage in the gene (TNFα, NFκB, TGFβ, VEGF, PKC) and protein expression (NFκB, VEGF) were noted in the kidney tissue alleviating the symptoms of DN. These results were further corroborated with histopathological results. Scientific data in the present study reveals that the combinations of mangiferin with the oral hypoglycemic drugs have been favorable in alleviating renal injury. Hence, a combination therapy to alleviate the vascular complication, diabetic nephropathy may be considered as a possible therapeutic strategy by including natural phytocompounds as an add on therapy to conventional oral hypoglycemic drugs.
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21 August 2022
A Correction to this paper has been published: https://doi.org/10.1007/s11033-022-07826-y
Abbreviations
- LPO:
-
Lipid peroxidation
- TBARS:
-
Thiobarbituric acid reactive substances
- SOD:
-
Superoxide dismutase
- GSH:
-
Glutathione
- GPx:
-
Glutathione peroxidase
- GST:
-
Glutathione S transferase
- PKC:
-
Protein kinase C
- NFκB:
-
Nuclear factor Kappa-light-chain-enhancer of activated B cells
- TNFα:
-
Tumor necrosis factor alpha
- TGFβ1:
-
Transforming growth factor beta 1
- VEGF:
-
Vascular endothelial growth factor
- GAPDH:
-
Glyceraldehyde 3-phosphate dehydrogenase
- RIPA:
-
Radioimmunoprecipitation assay
- SDS-PAGE:
-
Sodium dodecyl sulfate–polyacrylamide gel electrophoresis
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Acknowledgements
The histopathological and microphotographs prepared in CIDRF of MGMCRI are acknowledged with special mention. The authors also express their gratitude to UGC (SAP) and DST (FIST) grants for infrastructural facilities in the Department of Biotechnology, Pondicherry University and Dr. P. Shonima (Veterinarian), for helping in animal experimentation.
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HRV designed the study and edited the manuscript. VS performed the experiments and wrote the manuscript. SM and MR performed the animal experiments. BR performed the histopathological studies.
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Experimental protocol was approved by Institutional Animal Ethics Committee of Pondicherry University, India. (Approval No: PU/SLS/AH/2016/02).
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Sekar, V., Mani, S., Malarvizhi, R. et al. Positive interaction of mangiferin with selected oral hypoglycemic drugs: a therapeutic strategy to alleviate diabetic nephropathy in experimental rats. Mol Biol Rep 47, 4465–4475 (2020). https://doi.org/10.1007/s11033-020-05517-0
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DOI: https://doi.org/10.1007/s11033-020-05517-0