Sargahydroquinoic Acid, a Cyclooxygenase-2 Inhibitor, Attenuates Inflammatory Responses by Regulating NF- κB Inactivation and Nrf2 Activation in Lipopolysaccharide-Stimulated Cells

AbstractSargahydroquinoic acid (SHQA) is a major plastoquinone inSargassum macrocarpum and has shown the capacity to prevent inflammation and oxidative stress. However, the protective mechanisms were unclear. The molecular mechanisms of SHQA on ameliorating inflammation and oxidative stress have been investigated, using lipopolysaccharide (LPS)-stimulated macrophages. SHQA was isolated and purified fromS. macrocarpum and the anti-inflammatory mechanisms were explored using LPS-stimulated murine macrophage RAW 264.7 cells. SHQA did not change the expression of cyclooxygenase-2 (COX-2) but inhibited the activity of COX-2. As a result, SHQA significantly diminished the secretions of nitric oxide (NO), prostaglandin E2 (PGE2), and multiple pro-inflammatory cytokines. LPS-induced activation of nuclear factor- κB (NF-κB) was inhibited by SHQA by preventing the degradation of inhibitor κB-α (IκBα). NF-κB activation was also downregulated by the inhibition of Akt phosphorylation in LPS-stimulated cells. Furthermore, SHQA induced the expression of heme oxygenase 1via Nrf2 activation. These results indicated that SHQA inhibited LPS-induced expressions of inflammatory mediatorsvia suppressing the Akt-mediated NF- κB pathway as well as upregulating the Nrf2/HO-1 pathway. Our findings suggest that SHQA might be a potential therapeutic agent in various inflammatory diseases.
Source: Inflammation - Category: Allergy & Immunology Source Type: research