Related Experiment Video
Updated: Dec 14, 2025
Author Spotlight: Network Pharmacology and Molecular Docking to Decipher the Action of Jiawei Shengjiang San Against Diabetic Kidney Disease
Published on: May 10, 2024
Geraniol ameliorates diabetic nephropathy via interference with miRNA-21/PTEN/Akt/mTORC1 pathway in rats
Yasmin Ahmed Mohamed El-Said1, Nada Abdelmoneim Abdelhalium Sallam2, Afaf Abdel-Moniem Ain-Shoka2
1Department of Pharmacology and Toxicology, Faculty of Pharmacy, Cairo University, Cairo, Egypt. Yasmin.ahmed@pharma.cu.edu.eg.
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.
Insights
Geraniol, a natural compound, protects against diabetic nephropathy by improving kidney function and blood sugar. It modulates the miRNA-21/PTEN/Akt/mTORC1 pathway, reducing kidney damage in diabetic rats.
Area of Science:
- Nephrology
- Endocrinology
- Pharmacology
Background:
- Deregulated protein kinase B/mammalian target of rapamycin complex-1 (Akt/mTORC1) signaling drives diabetic nephropathy.
- Geraniol, an acyclic monoterpene, shows antidiabetic properties, but its renoprotective effects in diabetes are unknown.
Purpose of the Study:
- To investigate geraniol's renoprotective effects in diabetic nephropathy.
- To compare geraniol's efficacy against gliclazide, a standard antidiabetic drug.
- To elucidate geraniol's mechanism of action on the Akt/mTORC1 pathway.
Main Methods:
- Diabetic rats induced by streptozotocin were treated with geraniol or gliclazide for 6 weeks.
- Renal function, hyperglycemia, fibrotic markers, and redox balance were assessed.
- Expression of miRNA-21, PTEN, Akt, mTORC1, and downstream proteins was analyzed.
Main Results:
- Geraniol improved renal function (serum creatinine, BUN) and blood glucose levels, comparable to gliclazide.
- Geraniol suppressed fibrosis (TGF-β), inhibited lipid peroxidation, and restored redox balance.
- Geraniol downregulated miRNA-21, leading to PTEN/Akt/mTORC1 pathway reversion and reduced mesangial cell proliferation.
Conclusions:
- Geraniol exhibits significant renoprotective effects in diabetic nephropathy.
- Geraniol's mechanism involves modulating the miRNA-21/PTEN/Akt/mTORC1 pathway.
- Geraniol represents a potential therapeutic agent for diabetic kidney disease.
