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Garlic activates SIRT-3 to prevent cardiac oxidative stress and mitochondrial dysfunction in diabetes
Md Razia Sultana1, Pankaj K Bagul2, Parameshwar B Katare2
1Department of Medicinal Chemistry and Pharmacology, Indian Institute of Chemical Technology, Hyderabad 500007, India.
Background:
Cardiac complications are major contributor in the mortality of diabetic people. Mitochondrial dysfunctioning is a crucial contributor for the cardiac complications in diabetes, and SIRT-3 remains the major mitochondrial deacetylase. We hypothesized whether garlic has any role on SIRT-3 to prevent mitochondrial dysfunction in diabetic heart.
Methods:
Rats with developed hyperglycemia after STZ injection were divided into two groups; diabetic (Dia) and diabetic+garlic (Dia+Garl). Garlic was administered at a dose of 250mg/kg/day, orally for four weeks. An additional group was maintained to evaluate the effect of raw garlic administration on control rat heart.
Result:
We have observed altered functioning of cardiac mitochondrial enzymes involved in metabolic pathways, and increased levels of cardiac ROS with decreased activity of catalase and SOD in diabetic rats. Cardiac mRNA expression of TFAM, PGC-1α, and CO1 was also altered in diabetes. In addition, reduced levels of electron transport chain complexes that observed in Dia group were normalized with garlic administration. This indicates the presence of increased oxidative stress with mitochondrial dysfunctioning in diabetic heart. We have observed reduced activity of SIRT3 and increased acetylation of MnSOD. Silencing SIRT-3 in cells also revealed the same. However, administration of garlic improved the SIRT-3 and MnSOD activity, by deacetylating MnSOD. Increased SOD activity was correlated with reduced levels of ROS in garlic-administered rat hearts.
Conclusion:
Collectively, our results provide an insight into garlic's protection to T1DM heart through activation of SIRT3-MnSOD pathway.
Insights
Garlic protects the diabetic heart by activating the SIRT3-MnSOD pathway, improving mitochondrial function and reducing oxidative stress. This natural intervention normalizes enzyme activity and combats cardiac complications in diabetes.
Area of Science:
- Biochemistry
- Cardiology
- Nutraceuticals
Background:
- Diabetic cardiomyopathy is a significant cause of mortality.
- Mitochondrial dysfunction is a key factor in diabetic cardiac complications.
- Sirtuin-3 (SIRT3) is a major mitochondrial deacetylase implicated in this process.
Purpose of the Study:
- To investigate the potential protective role of garlic against mitochondrial dysfunction in the diabetic heart.
- To explore the effect of garlic on SIRT3 activity and its downstream targets.
Main Methods:
- Streptozotocin (STZ)-induced diabetic rat model.
- Administration of garlic (250mg/kg/day) orally for four weeks.
- Assessment of cardiac mitochondrial enzyme function, oxidative stress markers (ROS, catalase, SOD), and key gene/protein expression (TFAM, PGC-1α, CO1, SIRT3, MnSOD).
Main Results:
- Diabetic rats exhibited mitochondrial dysfunction, increased oxidative stress (ROS), and reduced antioxidant enzyme activity (catalase, SOD).
- SIRT3 activity was decreased, and MnSOD was acetylated in diabetic hearts.
- Garlic administration normalized electron transport chain complexes, enhanced SIRT3 and MnSOD activity, reduced ROS, and improved SOD activity.
Conclusions:
- Garlic demonstrates a protective effect on the diabetic heart.
- This protection is mediated through the activation of the SIRT3-MnSOD pathway.
- Garlic normalizes mitochondrial function and combats oxidative stress in diabetic cardiomyopathy.
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