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Broccoli sprout extract prevents diabetic cardiomyopathy via Nrf2 activation in db/db T2DM mice
Zheng Xu1,2, Shudong Wang1,2, Honglei Ji1
1Cardiovascular Center, the First Hospital of Jilin University, Changchun, China.
Abstract:
To develop a clinic-relevant protocol for systemic up-regulation of NFE2-related factor 2 (Nrf2) to prevent diabetic cardiomyopathy (DCM), male db/db and age-matched wild-type (WT) mice were given sulforaphane (SFN, an Nrf2 activator) and its natural source, broccoli sprout extract (BSE) by gavage every other day for 3 months, with four groups: vehicle (0.1 ml/10 g), BSE-low dose (estimated SFN availability at 0.5 mg/kg), BSE-high dose (estimated SFN availability at 1.0 mg/kg), and SFN (0.5 mg/kg). Cardiac function and pathological changes (hypertrophy, fibrosis, inflammation and oxidative damage) were assessed by echocardiography and histopathological examination along with Western blot and real-time PCR, respectively. Both BSE and SFN significantly prevented diabetes-induced cardiac dysfunction, hypertrophy and fibrosis. Mechanistically, BSE, like SFN, significantly up-regulated Nrf2 transcriptional activity, evidenced by the increased Nrf2 nuclear accumulation and its downstream gene expression. This resulted in a significant prevention of cardiac oxidative damage and inflammation. For all these preventive effects, BSE at high dose provided a similar effect as did SFN. These results indicated that BSE at high dose prevents DCM in a manner congruent with SFN treatment. Therefore, it suggests that BSE could potentially be used as a natural and safe treatment against DCM via Nrf2 activation.
Insights
Broccoli sprout extract (BSE) and sulforaphane (SFN) prevent diabetic cardiomyopathy (DCM) by activating Nrf2. High-dose BSE effectively mimics SFN
Area of Science:
- Cardiovascular Research
- Molecular Biology
- Nutritional Science
Background:
- Diabetic cardiomyopathy (DCM) is a significant complication of diabetes.
- NFE2-related factor 2 (Nrf2) activation offers a potential therapeutic target for DCM.
- Natural compounds like broccoli sprout extract (BSE) may activate Nrf2.
Purpose of the Study:
- To investigate the efficacy of BSE and sulforaphane (SFN) in preventing DCM.
- To establish a clinic-relevant protocol for Nrf2 up-regulation.
- To explore the mechanistic pathways involved in DCM prevention by BSE and SFN.
Main Methods:
- Male db/db and wild-type mice were treated with vehicle, BSE (low/high dose), or SFN for 3 months.
- Cardiac function was assessed using echocardiography.
- Cardiac pathology, oxidative stress, and inflammation were evaluated via histopathology, Western blot, and real-time PCR.
Main Results:
- Both BSE and SFN significantly prevented diabetes-induced cardiac dysfunction, hypertrophy, and fibrosis.
- BSE and SFN treatments increased Nrf2 nuclear accumulation and downstream gene expression.
- High-dose BSE demonstrated comparable preventive effects to SFN on cardiac oxidative damage and inflammation.
Conclusions:
- Broccoli sprout extract (BSE) effectively prevents diabetic cardiomyopathy (DCM) through Nrf2 activation.
- High-dose BSE shows similar efficacy to sulforaphane (SFN) in preventing DCM.
- BSE represents a potential natural and safe therapeutic strategy for DCM.
