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Diallyl trisulfide and diallyl disulfide ameliorate cardiac dysfunction by suppressing apoptotic and enhancing
Yao-Te Huang1, Chun-Hsu Yao, Chia-Li Way
1Department of Biological Science and Technology, China Medical University, Taichung, Taiwan.
Abstract:
Cardiovascular disease is one of the major causes of mortality in diabetic patients. Mounting studies have shown that garlic exhibits, possibly through its antioxidant potential, diverse biological activities. In this study, we investigated the alleviating effects of garlic oil (GO) and its two major components, diallyl disulfide (DADS) and diallyl trisulfide (DATS), on diabetic cardiomyopathy in rats. Physiological cardiac parameters were obtained using echocardiography. Apoptotic cells were evaluated using TUNEL and DAPI staining. Protein expression levels were determined using Western blotting analysis. Our findings indicated that in diabetic rat hearts significantly decreased fractional shortening percentage, increased levels of nitrotyrosine, an elevated number of TUNEL-positive cells, enhanced levels of caspase 3 expression, and decreased PI3K-Akt signaling pathway activities were observed. Furthermore, all of these alterations were reversed following both GO and DATS (or DADS) administrations through increasing PI3K-Akt signaling pathway activities and inhibiting both the death receptor-dependent and the mitochondria-dependent apoptotic pathways. In conclusion, this study shows that DATS and DADS, with the efficacy order DATS > DADS, have the therapeutic potential for ameliorating diabetic cardiomyopathy. Furthermore, the therapeutic effects of GO on diabetic cardiomyopathy should be mainly from DATS and DADS.
Insights
Garlic compounds diallyl trisulfide (DATS) and diallyl disulfide (DADS) show therapeutic potential for diabetic cardiomyopathy. These compounds, found in garlic oil, reverse cardiac dysfunction by inhibiting apoptosis and activating protective pathways.
Area of Science:
- Cardiology
- Biochemistry
- Pharmacology
Background:
- Cardiovascular disease is a leading cause of death in diabetic patients.
- Garlic and its compounds possess antioxidant and biological activities.
- Diabetic cardiomyopathy is a serious complication of diabetes.
Purpose of the Study:
- To investigate the effects of garlic oil (GO), diallyl disulfide (DADS), and diallyl trisulfide (DATS) on diabetic cardiomyopathy in rats.
- To elucidate the underlying mechanisms of GO, DADS, and DATS in ameliorating cardiac dysfunction.
Main Methods:
- Diabetic cardiomyopathy was induced in rats.
- Cardiac function was assessed using echocardiography.
- Apoptosis was evaluated via TUNEL and DAPI staining.
- Protein expression and signaling pathways (PI3K-Akt) were analyzed using Western blotting.
Main Results:
- Diabetic rats exhibited decreased cardiac function, increased oxidative stress (nitrotyrosine), elevated apoptosis (TUNEL-positive cells, caspase 3), and reduced PI3K-Akt activity.
- GO, DADS, and DATS treatments reversed these detrimental changes.
- Treatment increased PI3K-Akt signaling and inhibited both death receptor and mitochondria-dependent apoptotic pathways.
- Efficacy order was DATS > DADS.
Conclusions:
- DATS and DADS, major components of GO, demonstrate significant therapeutic potential for treating diabetic cardiomyopathy.
- The cardioprotective effects of GO are primarily attributed to DATS and DADS.
- These garlic compounds offer a promising therapeutic strategy by modulating apoptotic pathways and activating the PI3K-Akt signaling pathway.
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