The Role of Sulforaphane on Duchenne Muscular Dystrophy by Activation of Nrf2

Cheng-Cao Sun^1#, Jing-Yu Pan^1#, Shu-Jun Li^1,2 and De-Jia Li^1*

¹Department of Occupational and Environmental Health, School of Public Health, Wuhan University, 430071 Wuhan, P.R. China

²Wuhan Hospital for the Prevention and Treatment of Occupational Diseases, 430071 Wuhan, P.R. China

^#Cheng-Cao Sun and Jing-Yu Pan contribute equal to this work

^*Corresponding Author:

De-Jia Li
Department of Occupational and Environmental Health
School of Public Health, Wuhan University
No.115 Donghu Road, Wuchang District, Wuhan, P. R China
Tel: (86)18271470520
Fax: (86)02768778695
E-mail: lodjlwhu@sina.com

Received Date: August 09, 2015; Accepted Date: August 15, 2015; Published Date: August 20, 2015

Citation: Santini A, Raiola A, Meca G, Ritieni A (2015) The Role of Sulforaphane on Duchenne Muscular Dystrophy by Activation of Nrf2. Interdiscip J Microinflammation 3:e104. doi: 10.4172/2381-8727.1000e104

Copyright: © 2015 De-Jia Li, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

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Abstract

Sulforaphane (SFN) possesses powerful chemo-preventive effects and plays a crucial role on oxidative stress and inflammatory. In our recent study, SFN treatment could relieve muscular dystrophy in mdx mice by activating Nrf2 (NF-E2 related factor 2). Moreover, our findings indicated that SFN-activated Nrf2 alleviated muscle inflammation in dystrophin-deficient mdx mice through suppressing NF-κB signaling pathway. Collectively, SFNinduced Nrf2 molecular pathway might be a promising approach for treatment of the patients with Duchenne muscular dystrophy.

Keywords

Sulforaphane; Duchenne muscular dystrophy; Nrf2; Inflammation

Abbreviations

DMD: Duchenne Muscular Dystrophy; SFN: Sulforaphane; Nrf2: Nuclear Factor Erythroid 2-Related Factor 2; HO-1: Heme Oxygenase-1; ARE: Antioxidant Response Element; NQO1: NADH/ NADPH Quinone Oxidoreductase 1

Introduction

Duchenne muscular dystrophy (DMD) is the most common type of muscular dystrophy, which is also regarded as a severe muscle disease with an incidence of 1 in 3,500 live male newborns in the world [1-3]. The leading cause is dyctrophin gene mutations, which lose regulation of the muscle protein [4]. Cell death, progressive damage of muscle fibers, oxidative stress, and inflammation are the remarkable characteristics of DMD in humans and mdx mice [5]. Glucocorticoid play a role on boosting muscle function and strength in a short time in DMD therapy, but it is not effective and with plentiful side effects, like hypertension, diabetes, mood/behavioral affection for a long time using [6-8]. Therefore, there is not noticeably effective method for treatment of DMD yet.

Nrf2 (NF-E2 related factor 2) is one of the momentous transcription factors, which exists in biological body and affect genes expression of numerous oxidative stress proteins, detoxifying enzymes and antioxidant enzymes, et al [9,10]. Investigations show that Nrf2 is a promising protector against oxidative stress via activation of ARE and its downstream HO-1 and NQO1 [11,12]. Nrf2 could also prevent skeletal muscle from exhaustible exercise induced damage in rats via function of an antioxidant [13]. Additionally, some investigations demonstrate that Nrf2 might play a role of on anti-inflammation in a variety of tissues through inhibition of NF-κB signaling pathway [11,14]. Moreover, Nrf2 is also considered as a guardian in inflammation mediated airway response [15], emphysema [5] and colon cancer [16,17].

Sulforaphane (SFN) is described as glucoraphanin in many vegetables of brassicaceae family, which possesses powerful chemopreventive effects and is a useful isothiocyanate in our daily diet [18]. Increasing evidence shows that SFN attenuates oxidative stress by regulation of Nrf2 [19,20]. Furthermore, early studies indicate that the function of SFN is impacted via various mechanisms, such as inhibition of cell proliferation, promotion of apoptosis and suppression of metastasis and angiogenesis [9,21,22]. Although it has been demonstrated with chemo preventive function, the underlying efficacy of SFN on DMD has not been estimated yet.

Previous study indicated that SFN pretreatment alleviated liver damage in rats, owing to its powerful anti-oxidative efficay via activation of Nrf2-ARE signaling pathway [23]. In our recent studies, we explored the function of SFN on mdx mice, which are perceived as the perfect animal models for the pathogenesis research of DMD [1]. SFN treatment could promote gastrocnemius mass, myocardial hypertrophy and exercise capacity in mdx mice, meanwhile morphological features and body weight were also improved [24]. Moreover, we found the proteins and mRNAs of phase II detoxifying enzymes NQO1 and HO-1 of the signaling pathway Nrf2/ARE were significantly upregulated after SFN treatment in mdx mice [24-26]. We also found SFN treatment attenuated oxidative stress response and exercise-induced damage by activating Nrf2-ARE molecular pathway in mdx mice [24].

Inflammation is a critical factor that contributes to progressive damage of muscle and oxidative stress in DMD patients [27]. Therefore, it is urgent to investigate a useful approach to therapy inflammation of DMD patients. Many studies have indicated that Nrf2 protects various cells, tissues and organ systems against wide toxic insults and disease pathogenesis [28]. We explored the antiinflammatory function of SFN on mdx mice, our findings demonstrated that SFN played a pivotal role regarding treatment of inflammation in mdx mice, and improved the syndrome of dystrophic muscles [29]. The phenomenon might be attributed to inflammation relief in dystrophic muscles because we found numbers of immune cells were decreased in aspect of infiltration. Additionally, the levels of proinflammatory cytokines, such as IL-6, IL-1, TNF-α, and inflammatory cytokine CD45 were remarkably decreased and the potential mechanism might through repression of the NF-κB signaling pathway, which showed that the SFN had protective effects in muscular inflammation of mdx mice through Nrf2-mediated repression of NF-κB signaling pathway [29-32].

Taken together, SFN plays a crucial role on oxidative stress and chemopreventive effect, which could attenuate muscular dystrophy in mdx mice by activating Nrf2. Moreover, our findings indicated that SFN-inducedNrf2 alleviated muscle inflammation in dystrophindeficient mdx mice through suppression of NF-κB molecular pathway. Then we conclude that SFN-induced Nrf2 might be a promising approach for treatment of the patients with DMD. However, whether there is other mechanism or function of SFN in DMD need further investigate.

Funding

This work was supported by National Natural Science Foundation of China (No. 81271943) to Dejia Li, and the Fundamental Research Funds for the Central Universities (No. 2015305020202) to Chengcao Sun.

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