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

Zheng Xu,Lu Cai,Honglei Ji,Zhiguo Zhang,Shudong Wang,Kupper Wintergerst,Yi Tan,Jian Sun,Yang Zheng,Jing Chen

doi:10.1038/srep30252

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.

Highlights

Glutathione S-transferase, superoxide dismutase (SOD), catalase (CAT), and γ-glutamylcysteine synthetase[11,13]
To define whether broccoli sprout extract (BSE) and SFN protect against diabetes-induced cardiac dysfunction in db/db mice, we examined cardiac function by Echo and found that db/db mice had significantly decreased left ventricular (LV) internal systolic diameter (LVID; s), LV end systolic volume (LV vol; s), LV mass, ejection fraction (EF) and fractional shortening (FS) (Table 1)
Because accumulation of glycogen is regarded as a characteristic feature of diabetic cardiomyopathy (DCM), we examined the cardiac deposition of glycogen using periodic acid-Schiff (PAS) staining

Summary

Introduction

Glutathione S-transferase, superoxide dismutase (SOD), catalase (CAT), and γ-glutamylcysteine synthetase[11,13]. Nrf[2] activators have become an attractive approach for the prevention of diabetic complications[14,15]. As a potent Nrf[2] activator, SFN has been reported to prevent various diabetic complications in several animal models[18,19,20,21,22]. The effects of SFN directly used in human subjects on the prevention of diabetic complications have never been reported. There are no available data on the preventive effects of broccoli sprout preparation on diabetic cardiovascular complications. This study aimed to evaluate whether the chronic use of broccoli sprout extract (BSE), a natural SFN-rich supplement, can prevent the development of DCM. We found that BSE up-regulated Nrf[2] expression and transcription in the heart and significantly prevented the development of DCM

Objectives

Methods

Results

Conclusion