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Esculeoside A Decreases Diabetic Cardiomyopathy in Streptozotocin-Treated Rats by Attenuating Oxidative Stress,
Jozaa Z ALTamimi1, Nora A AlFaris1, Ghedeir M Alshammari2
1Department of Physical Sports Sciences, College of Education, Princess Nourah bint Abdulrahman University, Riyadh 11671, Saudi Arabia.
Abstract:
Background and Objectives: This experiment evaluated the preventative influence of the tomato-derived Esculeoside A (ESA) on diabetic cardiomyopathy in type 1 diabetes mellitus (T1DM) in rats induced by streptozotocin (STZ). It also examined whether the activation of Nrf2 signaling affords this protection. Materials and Methods: Adult male Wistar control nondiabetic rats and rats with T1DM (STZ-T1DM) were given either carboxymethylcellulose as a vehicle or ESA (100 mg/kg) (eight rats/group) orally daily for 12 weeks. A group of STZ-T1DM rats was also treated with 100 mg/kg ESA and co-treated i.p. with 2 mg/kg (twice/week), brusatol, and Nrf2 inhibitors for 12 weeks. Results and Conclusions: Treatment with ESA prevented the gain in heart weight and cardiomyocyte hypertrophy and improved the left ventricular (LV) systolic and diastolic function (LV) in the STZ-T1DM rat group. Likewise, it reduced their serum levels of triglycerides, cholesterol, and low-density lipoproteins (LDL-c), as well as their LV mRNA, cytoplasmic total, and nuclear total levels of NF-κB. ESA also reduced the total levels of malondialdehyde, tumor necrosis factor-α, interleukine-6 (IL-6), Bax, cytochrome-c, and caspase-3 in the LV of the STZ-T1DM rats. In parallel, ESA enhanced the nuclear and cytoplasmic levels of Nrf2 and the levels of superoxide dismutase, glutathione, and heme oxygenase-1, but decreased the mRNA and cytoplasmic levels of keap-1 in the LVs of the STZ-T1DM rats. Interestingly, ESA did not affect the fasting insulin and glucose levels of the diabetic rats. All of these beneficially protective effects of ESA were not seen in the ESA-treated rats that received brusatol. In conclusion, ESA represses diabetic cardiomyopathy in STZ-diabetic hearts by activating the Nrf2/antioxidant/NF-κB axis.
Insights
Esculeoside A (ESA), a tomato compound, prevents diabetic cardiomyopathy in rats by activating Nrf2 signaling. This protects heart function and reduces inflammation without affecting blood glucose levels.
Area of Science:
- Cardiology
- Endocrinology
- Pharmacology
Background:
- Diabetic cardiomyopathy is a serious complication of type 1 diabetes mellitus (T1DM).
- Streptozotocin (STZ)-induced T1DM in rats is a common model for studying diabetic complications.
- Esculeoside A (ESA), derived from tomatoes, has shown potential therapeutic properties.
Purpose of the Study:
- To evaluate the preventative effects of ESA on diabetic cardiomyopathy in STZ-induced T1DM rats.
- To investigate the role of Nrf2 signaling activation in mediating ESA's protective effects.
Main Methods:
- Adult male Wistar rats were induced with T1DM using STZ.
- Rats received daily oral administration of ESA (100 mg/kg) or vehicle for 12 weeks.
- A subset of ESA-treated rats received brusatol, an Nrf2 inhibitor, to assess the pathway's involvement.
Main Results:
- ESA treatment prevented cardiac hypertrophy and improved left ventricular function in STZ-T1DM rats.
- ESA reduced serum lipids, oxidative stress markers (malondialdehyde), and inflammatory cytokines (TNF-α, IL-6) in the heart.
- ESA upregulated Nrf2 and antioxidant enzymes (SOD, GSH, HO-1) while downregulating Keap-1 and NF-κB in the heart.
Conclusions:
- ESA effectively prevents diabetic cardiomyopathy in a rat model of T1DM.
- The cardioprotective effects of ESA are mediated through the activation of the Nrf2/antioxidant/NF-κB signaling pathway.
- ESA demonstrates therapeutic potential for managing diabetic heart complications.
