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Abstract
Background
Diabetic nephropathy (DN), an end-stage renal disorder, has posed a menace to humankind globally, because of its complex nature and poorly understandable intricate mechanism. In recent times, functional foods as potential health benefits have been gaining attention of consumers and researchers alike. Rich in antioxidants, the peel and seed of pomegranate have previously demonstrated protection against oxidative-stress-related diseases, including cardiovascular disorders, diabetes, and cancer.
Purpose
This study was designed to investigate the ameliorative role of pomegranate peel extract–stabilized gold nanoparticle (PPE-AuNP) on streptozotocin (STZ)-induced DN in an experimental murine model.
Methods
Following the reduction methods, AuNP was prepared using the pomegranate peel ellagitannins and characterized by particle size, physical appearance, and morphological architecture. Modulatory potential of PPE-AuNP was examined through the plethora of biochemical and high throughput techniques, flow cytometry, immunoblotting, and immunofluorescence.
Results
The animals treated with PPE-AuNP markedly reduced the fasting blood glucose, renal toxicity indices, and serum TC and TG in a hyperglycemic condition. As evident from an increased level of plasma insulin level, PPE-AuNP normalized the STZ-induced pancreatic β-cell dysfunction. The STZ-mediated suppression of endogenous antioxidant response was restored by the PPE-AuNP treatment, which reduced the generation of LPO as well as iROS. Furthermore, the hyperglycemia-mediated augmentation of protein glycation, followed by the NOX4/p-47phox activation, diminished with the application of PPE-AuNP. The histological and immunohistochemical findings showed the protective efficacy of PPE-AuNP in reducing STZ-induced glomerular sclerosis and renal fibrosis. In addition, it reduced proinflammatory burden through the modulation of the MAPK/NF-κB/STAT3/cytokine axis. Simultaneously, PI3K/AKT-guided Nrf2 activation was evident upon the PPE-AuNP application, which enhanced the antioxidant response and maintained hyperglycemic homeostasis.
Conclusion
The findings indicate that the use of PPE-AuNPs might act as an economic therapeutic remedy for alleviating DN.
Acknowledgments
The research is supported by the National Medicinal Plant Board (NMPB), Ministry of Ayurveda, Yoga & Naturopathy, Unani, Siddha and Homoeopathy (AYUSH), Government of India. A research fellowship from University Grants Commission-Department of Atomic Energy (UGC-DAE), Government of India, to Mr Snehasis Mishra is gratefully acknowledged. The authors gratefully acknowledge Dr Suparna Banerjee for the improvement of English usage. In addition, the authors are also thankful to Mr Tanmoy Dalui, Mrs Debalina Chakraborty, Sri. Binayak Pal, and Smt. Banasri Das of Central Instrumentation Facility, Council of Scientific & Industrial Research–Indian Institute of Chemical Biology for providing flow cytometer and confocal microscope facilities. The authors are very obliged to Dr Asim Bhowmik for his guidance in some parts of this study.
Disclosure
The authors report no conflicts of interest in this work.