ABSTRACT
Objective To investigate the effect of the asthmatic mice's contents of nuclear factorerythroid-2-related factor 2,Nrf2 and HO-1 reated with curcumin in lung tissue.Methods All 45 mice were divided into three teams randomly,the normal mice,the asthmatic mice and the curcumin mice group.We tested the expression of Nrf2 and HO-1 of three mice teams in lung by immunolfluorescence technique.We tested the protein contents of Nrf2 and HO-1 of the three teams in the lung tissue by Western blot.We tested the binding activity of Nrff2 and ARE of the three teams in lung by EMSA.Results The expression of Nrf2 and HO-1 in curcumin group was significantly higher than that in asthma group and normal control group by immunolfluorescence technique.There was no sigrnificant difference in content of cytoplasm Nrf2 protein in lung tissue between three groups by western blot(P ＞ 0.05).The content of nuclear Nrf2 and HO-1 protein in the lung tissue of the curcumin group was significantly higher than that in the other two groups,the difference is statistically significant (Nrf2,P ＜0.05;HO-1,P ＜0.01).The binding activity of Nrf2-ARE in lung tissue of curcumin group was significantly higher than that of asthma group and control group,with statistical significance(P ＜ 0.05).Conclusion Curcumin can increase the protein contents of the Nrf2 and HO-1 of mice and enhance the expression of them.
ABSTRACT
Dimethyl fumarate (DMF) is a novel oral immunomodulatory and neuroprotective drug that was approved by FDA for relapsing forms of multiple sclerosis (MS). The initial use of DMF was for the treatment of psoriasis where its long-term use was safe and efficacious, and it also got German approval for the same. It was found that the anti-inflammatory actions of DMF contributed to its efficacy in psoriasis. This anti-inflammatory action of DMF created interest using DMF in other auto-immune or inflammatory diseases, including MS. DMF acts by decreasing production and release of inflammatory molecules. DMF also activates the nuclear factor-erythroid 2 related factor pathway which induces the transcription of various genes, including anti-oxidative ones, reduces oxidative neuronal death and helps maintain myelin integrity. Thus, DMF acts via two pathways: by down-regulating oxidative stress and corresponding cellular injury, as well as by inhibiting pro-inflammatory cytokines. DMF is an orally administered, enteric-coated microtablet preparation. There was a 44-53% reduction in annualized relapse rate with the use of DMF in patients with relapsing form of MS. The most common adverse reactions reported are flushing, abdominal pain, diarrhea, and nausea, which are more prominent during initial treatment and usually decrease over time. No serious adverse events were seen during the phase II and III trials, including no increased risk of opportunistic infections or cancer. DMF seems to approach the ideal combination of safety, efficacy and welltolerability to other approved oral therapies for MS.