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Geraniol ameliorates diabetic nephropathy via interference with miRNA-21/PTEN/Akt/mTORC1 pathway in rats

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Abstract

Deregulated activity of protein kinase B/mammalian _target of rapamycin complex-1 (Akt/mTORC1) incites crucial pathological characteristics of diabetic nephropathy. The acyclic monoterpene geraniol has been recently reported to possess antidiabetic effects; however, its potential renoprotective effect in diabetes has not yet been elucidated. This study aimed to assess the possible modulatory effect of geraniol on the Akt/mTORC1 pathway in diabetes-induced nephropathy in rats compared to the standard antidiabetic drug gliclazide. Geraniol and gliclazide was administered daily to diabetic rats for 6 weeks starting on the 3rd-day post diabetes induction by streptozotocin (STZ). Geraniol amended the deteriorated renal function (serum creatinine; blood urea nitrogen). It exerted a remarkable antihyperglycemic effect that is comparable to that of gliclazide and suppressed the fibrotic marker, transforming growth factor-β. Geraniol restored redox balance and inhibited lipid peroxidation by reducing nicotine amide adenine dinucleotide phosphate oxidase and enhancing the antioxidant enzyme, superoxide dismutase. These beneficial effects were associated with a robust downregulation of miRNA-21 and consequently, reversion of tumor suppressor protein phosphatase and tension homolog (PTEN)/Akt/mTORC1 cue and its downstream proteins required for mesangial cell proliferation and matrix protein synthesis. The current study indicates that geraniol interfered with miRNA-21/ PTEN/AKT/mTORC1 pathway signaling that contributes largely to the progression of mesangial expansion and extracellular matrix deposition in diabetic nephropathy.

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Acknowledgments

The authors are grateful to Assoc. Prof. Mohamed A. Salaheldin, Department of Cytology and Histology, Faculty of Veterinary Medicine, Cairo University, for his efforts in performing and explaining the histopathological examinations.

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  1. Department of Pharmacology and Toxicology, Faculty of Pharmacy, Cairo University, Cairo, Egypt

    Yasmin Ahmed Mohamed El-Said, Nada Abdelmoneim Abdelhalium Sallam, Afaf Abdel-Moniem Ain-Shoka & Hekma Abdel-Tawab Abdel-Latif

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  2. Nada Abdelmoneim Abdelhalium Sallam
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Contributions

Yasmin A. Mohamed, Nada A. Sallam, Afaf A. Ain-Shoka, and Hekma A. Abdel-Latif conceived and designed the original idea of the research. Yasmin A. Mohamed conducted the experiments, carried out the statistical analyses, and wrote the manuscript. Yasmin A. Mohamed and Nada A. Sallam modified the manuscript. All authors read and approved the manuscript. All data were generated in-house and no paper mill was used.

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Correspondence to Yasmin Ahmed Mohamed El-Said.

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Animal use and care procedures were approved by the Ethical Committee for Animal Experimentation at Faculty of Pharmacy, Cairo University and concur with the US National Institutes of Health guide for the Care and Use of Laboratory Animals.The ariticle doesn't include human participants.This part is presented in the animals section in the mateial and methods section.

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El-Said, Y.A.M., Sallam, N.A.A., Ain-Shoka, A.AM. et al. Geraniol ameliorates diabetic nephropathy via interference with miRNA-21/PTEN/Akt/mTORC1 pathway in rats. Naunyn-Schmiedeberg's Arch Pharmacol 393, 2325–2337 (2020). https://doi.org/10.1007/s00210-020-01944-9

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