Broccoli sprout extract prevents diabetic cardiomyopathy via Nrf2 activation in db/db T2DM mice

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.

Inhibition of HDAC3 prevents diabetic cardiomyopathy in OVE26 mice via epigenetic regulation of DUSP5-ERK1/2 pathway

“…Echocardiography was performed as we described previously (23). In brief, heart rate (HR), parasternal long-axis and short-axis views in mice anesthetized with isoflurane were recorded by transthoracic echocardiography (Vevo 770, Visual Sonics, Canada) equipped with a high-frequency ultrasound probe (RMV-707B).…”

The Effect of Nrf2 on Diabetic Complications

“…Key dietary bioactive activators of this system are glucosinolate-derived dietary isothiocyanates (SFN) and indoles, thioethers and disulides, polyphenols, lavonoids, carotenoids, oxidized omega-3 faty acids, and triterpenoids. Additionally, SFN is found in the brassica vegetables (broccoli, cabbage, caulilower, Brussel sprouts, and others) and rocket salad [11]. The diet as a source of anti-inlammatory and health-beneicial compounds for patients with chronic renal failure has been recognized.…”

“…The ROS-mediated biological signaling pathways could be afected by enhanced Nrf2-ARE activity because ROS signaling intermediates should inversely correlate with the ROS scavenging activity and antioxidant status in cells. Thus, when the cells are chronically exposed to oxidative stressors, cellular ROS scavenging capacity is adaptively upregulated, primarily through the activation of Nrf2 and subsequent transcriptional induction of a suite of antioxidant enzymes [11].…”

“…Treatment with SFN-rich BSE for 3 months could signiicantly prevent the pathological process of DCM in the T2DM mice model, and like SFN, BSE also signiicantly upregulated Nrf2 expression and function to prevent diabetes-induced cardiac oxidative stress and inlammation. Therefore, BSE could potentially be used as a natural and safe treatment against DCM via Nrf2 activation [11].…”

“…On the other hand, the interplay of these factors is not yet understood. The single nucleotide polymorphisms (SNPs) are a common type of genetic variations, which have been shown to impact most population susceptibility to diseases and individual response to drug treatments [10,11].…”