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

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 e...

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Main Authors: Xu, Zheng, Wang, Shudong, Ji, Honglei, Zhang, Zhiguo, Chen, Jing, Tan, Yi, Wintergerst, Kupper, Zheng, Yang, Sun, Jian, Cai, Lu
Format: Online
Language:English
Published: Nature Publishing Group 2016
Online Access:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4960533/
id pubmed-4960533
recordtype oai_dc
spelling pubmed-49605332016-08-05 Broccoli sprout extract prevents diabetic cardiomyopathy via Nrf2 activation in db/db T2DM mice Xu, Zheng Wang, Shudong Ji, Honglei Zhang, Zhiguo Chen, Jing Tan, Yi Wintergerst, Kupper Zheng, Yang Sun, Jian Cai, Lu Article 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. Nature Publishing Group 2016-07-26 /pmc/articles/PMC4960533/ /pubmed/27457280 http://dx.doi.org/10.1038/srep30252 Text en Copyright © 2016, The Author(s) http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
repository_type Open Access Journal
institution_category Foreign Institution
institution US National Center for Biotechnology Information
building NCBI PubMed
collection Online Access
language English
format Online
author Xu, Zheng
Wang, Shudong
Ji, Honglei
Zhang, Zhiguo
Chen, Jing
Tan, Yi
Wintergerst, Kupper
Zheng, Yang
Sun, Jian
Cai, Lu
spellingShingle Xu, Zheng
Wang, Shudong
Ji, Honglei
Zhang, Zhiguo
Chen, Jing
Tan, Yi
Wintergerst, Kupper
Zheng, Yang
Sun, Jian
Cai, Lu
Broccoli sprout extract prevents diabetic cardiomyopathy via Nrf2 activation in db/db T2DM mice
author_facet Xu, Zheng
Wang, Shudong
Ji, Honglei
Zhang, Zhiguo
Chen, Jing
Tan, Yi
Wintergerst, Kupper
Zheng, Yang
Sun, Jian
Cai, Lu
author_sort Xu, Zheng
title Broccoli sprout extract prevents diabetic cardiomyopathy via Nrf2 activation in db/db T2DM mice
title_short Broccoli sprout extract prevents diabetic cardiomyopathy via Nrf2 activation in db/db T2DM mice
title_full Broccoli sprout extract prevents diabetic cardiomyopathy via Nrf2 activation in db/db T2DM mice
title_fullStr Broccoli sprout extract prevents diabetic cardiomyopathy via Nrf2 activation in db/db T2DM mice
title_full_unstemmed Broccoli sprout extract prevents diabetic cardiomyopathy via Nrf2 activation in db/db T2DM mice
title_sort broccoli sprout extract prevents diabetic cardiomyopathy via nrf2 activation in db/db t2dm mice
description 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.
publisher Nature Publishing Group
publishDate 2016
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4960533/
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