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Combined Effects of Metformin, Quercetin, and Fractionated Gamma Irradiation on MiR-107-Mediated Brain Injury in
Omayma A R Abozaid1, Fatma S M Moawed2, Hanaa F B Gabr1
1Faculty of Veterinary Medicine, Biochemistry and Molecular Biology Department, Benha University, Benha, Egypt.
Abstract:
Objectives: MiR-107 upregulation represents a key target among the multiple pathways associated with T2DM. Given that drug combinations offer significant therapeutic potential, this study investigated the antidiabetic, antioxidant, and anti-inflammatory effects of γ-irradiation, the quercetin (common flavonol), and the metformin (biguanide) on HFD/STZ-induced diabetic rats' brains. Methods: Diabetic rats were treated with metformin (200 mg/kg b.w./day) alone or in combination with quercetin (30 mg/kg b.w./day) and/or γ-radiation (fractionated 4 Gy) for 4 weeks. Results: The diabetic group exhibited increased body weight, blood glucose, HOMA-IR, AChE, MMP-2, and lipid peroxidation, while serum insulin and brain GPx antioxidant enzyme activity were significantly decreased. Similarly, BDNF and SIRTI transcript levels and IRS1 protein expression were reduced, whereas NF-κB and MiR-107 transcript levels were elevated in diabetic rats compared to controls. Histopathological examination of diabetic brain tissue corroborated the biochemical findings. Treatment with metformin alone or in combination with γ-irradiation and/or quercetin effectively mitigated these effects by downregulating miR-107 and improving brain function, with optimal results achieved through combined therapy. Conclusion: The synergistic combination of Metformin, fractionated gamma-irradiation, and quercetin effectively attenuates brain injury in diabetic rats by enhancing IRS1/SIRT1/BDNF signaling while suppressing MiR-107/NF-κB pathways.
Insights
This study shows that a combination of metformin, gamma irradiation, and quercetin effectively protects diabetic rat brains. This therapy reduces inflammation and oxidative stress, offering a potential treatment for diabetic brain complications.
Area of Science:
- Neuroscience
- Biochemistry
- Pharmacology
Background:
- Type 2 diabetes mellitus (T2DM) is linked to neurological complications.
- MiR-107 upregulation is a key factor in T2DM-associated pathways.
- Combination therapies may offer significant therapeutic potential for T2DM.
Purpose of the Study:
- To investigate the effects of metformin, quercetin, and gamma irradiation on diabetic rat brains.
- To evaluate the antidiabetic, antioxidant, and anti-inflammatory properties of these agents.
- To explore their combined therapeutic potential in mitigating T2DM-induced brain injury.
Main Methods:
- Diabetic rats (HFD/STZ-induced) were treated with metformin, quercetin, and/or gamma irradiation for 4 weeks.
- Biochemical markers, including blood glucose, insulin, oxidative stress enzymes, and inflammatory markers, were assessed.
- Gene and protein expression levels (BDNF, SIRT1, IRS1, NF-κB, MiR-107) and brain histopathology were analyzed.
Main Results:
- Diabetic rats showed increased body weight, blood glucose, HOMA-IR, AChE, MMP-2, lipid peroxidation, NF-κB, and MiR-107.
- Decreased levels of serum insulin, GPx, BDNF, SIRT1, and IRS1 were observed in diabetic rats.
- Combined therapy significantly mitigated these adverse effects, downregulating miR-107 and improving brain function.
Conclusions:
- Metformin, gamma irradiation, and quercetin synergistically attenuate brain injury in diabetic rats.
- The combination therapy enhances IRS1/SIRT1/BDNF signaling pathways.
- This treatment strategy effectively suppresses MiR-107/NF-κB pathways, offering neuroprotection in T2DM.
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