title: 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.
authors.affiliation: Cardiovascular Center, the First Hospital of Jilin University, Changchun, China.|Kosair Children's Hospital Research Institute, Department of Pediatrics, University of Louisville, Louisville, KY, USA.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Xu
authors.affiliation: Cardiovascular Center, the First Hospital of Jilin University, Changchun, China.|Kosair Children's Hospital Research Institute, Department of Pediatrics, University of Louisville, Louisville, KY, USA.
authors.forename: Shudong
authors.initials: S
authors.lastname: Wang
authors.affiliation: Cardiovascular Center, the First Hospital of Jilin University, Changchun, China.
authors.forename: Honglei
authors.initials: H
authors.lastname: Ji
authors.affiliation: Cardiovascular Center, the First Hospital of Jilin University, Changchun, China.
authors.forename: Zhiguo
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Kosair Children's Hospital Research Institute, Department of Pediatrics, University of Louisville, Louisville, KY, USA.
authors.forename: Jing
authors.initials: J
authors.lastname: Chen
authors.affiliation: Kosair Children's Hospital Research Institute, Department of Pediatrics, University of Louisville, Louisville, KY, USA.|Wendy Novak Diabetes Care Center, University of Louisville, Louisville, KY, USA.
authors.forename: Yi
authors.initials: Y
authors.lastname: Tan
authors.affiliation: Wendy Novak Diabetes Care Center, University of Louisville, Louisville, KY, USA.|Division of Endocrinology, Department of Pediatrics, the University of Louisville, Louisville, KY, USA.
authors.forename: Kupper
authors.initials: K
authors.lastname: Wintergerst
authors.affiliation: Cardiovascular Center, the First Hospital of Jilin University, Changchun, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Zheng
authors.affiliation: Cardiovascular Center, the First Hospital of Jilin University, Changchun, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Sun
authors.affiliation: Kosair Children's Hospital Research Institute, Department of Pediatrics, University of Louisville, Louisville, KY, USA.|Wendy Novak Diabetes Care Center, University of Louisville, Louisville, KY, USA.
authors.forename: Lu
authors.initials: L
authors.lastname: Cai
mesh_terms: D000818:Animals; D001937:Brassica / Q000737:chemistry; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D058065:Diabetic Cardiomyopathies / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D004195:Disease Models, Animal; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D017879:Isothiocyanates / Q000008:administration & dosage; D051379:Mice; D016688:Mice, Inbred NOD; D051267:NF-E2-Related Factor 2 / Q000819:agonists / Q000235:genetics*; D010084:Oxidation-Reduction / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects; D010936:Plant Extracts / Q000008:administration & dosage* / Q000737:chemistry; D013454:Sulfoxides
chemical_list: D017879:Isothiocyanates; D051267:NF-E2-Related Factor 2; C495636:Nfe2l2 protein, mouse; D010936:Plant Extracts; D013454:Sulfoxides; C016766:sulforaphane