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

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

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 effec...

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Bibliographic Details
Published in:Naunyn-Schmiedeberg's archives of pharmacology Vol. 393; no. 12; pp. 2325 - 2337
Main Authors: El-Said, Yasmin Ahmed Mohamed, Sallam, Nada Abdelmoneim Abdelhalium, Ain-Shoka, Afaf Abdel-Moniem, Abdel-Latif, Hekma Abdel-Tawab
Format: Journal Article
Language:English
Published: Berlin/Heidelberg Springer Berlin Heidelberg 01-12-2020
Springer Nature B.V
Subjects:
Adenine
AKT protein
Antidiabetics
Antioxidants
Biomedical and Life Sciences
Biomedicine
Cell proliferation
Creatinine
Diabetes
Diabetes mellitus
Diabetic nephropathy
Extracellular matrix
Kinases
Lipid peroxidation
Matrix protein
miRNA
Nephropathy
Neurosciences
Nicotine
Original Article
Pharmacology/Toxicology
Protein biosynthesis
Protein phosphatase
Proteins
PTEN protein
Rapamycin
Renal function
Streptozocin
Superoxide dismutase
TOR protein
Transforming growth factor-b
Tumor suppressor genes
Urea
Mesangial expansion
Diabetic nephropathy
mTORC1
miRNA-21
Geraniol
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Summary: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.
ISSN:0028-1298
1432-1912
DOI:10.1007/s00210-020-01944-9