Dysiarenone From Marine Sponge Dysidea Arenaria Attenuates Ros And Inflammation Via Inhibition Of 5-Lox/Nf-Kappa B/Mapks And Upregulation Of Nrf-2/Oh-1 In Raw 264.7 Macrophages

Background: Marine natural products harbor a variety of pharmacological activities, and the sea species have been becoming a main source of new drug candidate. In pursuit of safer and more effective anti-inflammation drug, the anti-inflammatory activities, anti-oxygenation effects and underlying molecular mechanisms of compound dysiarenone from Dysidea arenaria were investigated via LPS-induced RAW 264.7 cell model.Methods: Firstly, RAW 264.7 cells have been stimulated with LPS and treated with dysiarenone, and the cell viability of the LPS-treated RAW 264.7 cells was examined. One-step method, DCFH-DA fluorescence probe method was used to detect reactive oxygen species (ROS). The modulation of dysiarenone on anti-inflammation was detected by enzyme-linked immunosorbent assay by measuring the release of inflammatory cytokines (TNF-alpha and IL-6), and inflammatory mediators (LTB4). Further, the underlying anti-inflammatory mechanism of dysiarenone was explored by determining the expression of inducible 5-LOX, MAPKs, p-Akt, and p-NF-kappa B p65. Oxidative stress is tightly connected with inflammation, which was also evaluated through nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (OH-1) signaling pathway.Results: Our study unraveled that dysiarenone between 2 and 8 mu M reduces the inflammation responses via suppressing the production of inflammatory cytokines (TNF-alpha and IL-6) and inflammatory mediators (LTB4). Dysiarenone down-regulated the protein levels of inducible 5-LOX via the inhibition of phosphorylation of MAPKs (including p38, ERK), Akt and NF-kappa B p65. Additionally, dysiarenone decreases ROS accumulation by upregulating HO-1 expression via nuclear translocation of Nrf2.Conclusion: In conclusion, we demonstrated that dysiarenone possesses anti-inflammation and anti-oxidation activity via inhibiting 5-LOX/NF-kappa B/MAPK and Nrf2/HO-1 signaling pathway. Dysiarenone might be a promising lead compound for inflammatory diseases.