Sulforaphane induced Nrf2 can alleviate muscle inflammation in mdx mice by inhibiting NF-κB signaling pathway. - GreenMedInfo Summary
Sulforaphane attenuates muscle inflammation in dystrophin-deficient Mdx mice via Nrf2-mediated inhibition of NF-κB signaling pathway.
J Biol Chem. 2015 May 26. Epub 2015 May 26. PMID: 26013831
Cheng-Cao Sun
Inflammation is widely distributed in patients with Duchenne muscular dystrophy (DMD), and ultimately leads to progressive deterioration of muscle function with chronic muscle damage, oxidative stress and reduced oxidative capacity. NF-E2-related factor 2 (Nrf2) plays a critical role in defending against inflammation in different tissues via activation of phase II enzymes, heme oxygenase-1 (HO-1), and inhibition of NF-κB signaling pathway. However, the role of Nrf2 in the inflammation of dystrophic muscle remains unknown. To determine whether Nrf2 may counteract inflammation in dystrophic muscle, we treated 4-week-old male mdx mice with Nrf2 activator sulforaphane (SFN) by gavage (2 mg/kg body weight per day) for 4 weeks. The experimental results demonstrated that SFN treatment increased the expression of muscle phase II enzymes HO-1 with Nrf2 dependent manner. Inflammation in mice was reduced by SFN treatment as indicated by decreased infiltration of immune cell and expression of the inflammatory cytokines CD45, pro-inflammatory cytokines tumor necrosis factor-α, interleukin-1β and interleukin-6 in the skeletal muscles of mdx mice. In addition, SFN treatment also decreased the expression of NF-κB (p65) and phosphorylate-IκB kinase(IKK)-α,as well as increased inhibitor of κB (IκB)-α expression in mdx mice with Nrf2 dependent manner. Collectively, these results show that SFN-induced Nrf2 can alleviate muscle inflammation in mdx mice by inhibiting NF-κB signaling pathway.