Sulforaphane alleviates muscular dystrophy inmdxmice by activation of Nrf2

Abstract

Sulforaphane (SFN), one of the most important isothiocyanates in the human diet, is known to have chemo-preventive and antioxidant activities in different tissues via activation of nuclear factor erythroid 2-related factor 2 (Nrf2)-mediated induction of antioxidant/phase II enzymes, such as heme oxygenase-1 and NAD(P)H quinone oxidoreductase 1. However, its effects on muscular dystrophy remain unknown. This work was undertaken to evaluate the effects of SFN on Duchenne muscular dystrophy. Four-week-old mdx mice were treated with SFN by gavage (2 mg·kg body wt(-1)·day(-1) for 8 wk), and our results demonstrated that SFN treatment increased the expression and activity of muscle phase II enzymes NAD(P)H quinone oxidoreductase 1 and heme oxygenase-1 with a Nrf2-dependent manner. SFN significantly increased skeletal muscle mass, muscle force (∼30%), running distance (∼20%), and GSH-to-GSSG ratio (∼3.2-fold) of mdx mice and decreased the activities of plasma creatine phosphokinase (∼45%) and lactate dehydrogenase (∼40%), gastrocnemius hypertrophy (∼25%), myocardial hypertrophy (∼20%), and malondialdehyde levels (∼60%). Furthermore, SFN treatment also reduced the central nucleation (∼40%), fiber size variability, and inflammation and improved the sarcolemmal integrity of mdx mice. Collectively, these results show that SFN can improve muscle function and pathology and protect dystrophic muscle from oxidative damage in mdx mice associated with Nrf2 signaling pathway, which indicate Nrf2 may have clinical implications for the treatment of patients with muscular dystrophy.

Sulforaphane Treatment of Stress Urinary Incontinence Via the Nrf2-ARE Pathway in a Rat Model

“…Therefore, we suggest that SFN may improve urinary function, not by restraining muscle cell apoptosis, but by preserving muscle function. Similar to other reported studies [29] [40], SFN could improve muscle contractile function, preserve the normal muscle morphology, protect muscles from oxidative damage, and decrease collagen expression. The precise mechanism through which SFN influences the urethral sphincter muscle should be further explored.…”

“…While various studies have demonstrated the promising potential of SFN for the treatment of numerous diseases [28, 29], the present study may be the first to explore the feasibility of SFN for SUI treatment.…”

Hsa-miR-329 exerts tumor suppressor function through down-regulation of MET in non-small cell lung cancer

“…Cell lysates were centrifuged at 12,000× g for 20 min at 4°C, and the protein concentrations of the supernatant were determined using the BCA protein assay reagent kit (Thermo) [44-47]. The supernatants containing total protein were then mixed with a corresponding volume of 5× SDS loading buffer and heated at 100°C for 10 min.…”

Insights into the Pathogenic Secondary Symptoms Caused by the Primary Loss of Dystrophin

“…Thus, Nrf2 represents a potential therapeutic target for DMD. Indeed, the induction of Nrf2, by the Nrf2 activator sulforaphane (SFN), was shown to reduce muscle inflammation and fibrosis in dystrophic mice, thereby improving muscle function [74][75][76]. The central role of the Nrf2 pathway in DMD pathophysiology is further supported by clinical studies in which the expression of Nrf2 was found to be upregulated in very young DMD patients early before the appearance of symptoms but not during the progression of disease, when the severity of muscular dystrophy is clearly observed [77].…”