Inhibitory Effects of Benzaldehyde Derivatives from the Marine Fungus Eurotium sp. SF-5989 on Inflammatory Mediators via the Induction of Heme Oxygenase-1 in Lipopolysaccharide-Stimulated RAW264.7 Macrophages

摘要

Two benzaldehyde derivatives, flavoglaucin (>1) and isotetrahydro-auroglaucin (>2), were isolated from the marine fungus Eurotium sp. SF-5989 through bioassay- and ¹H NMR-guided investigation. In this study, we evaluated the anti-inflammatory effects of these compounds in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages. We demonstrated that compounds >1 and >2 markedly inhibited LPS-induced nitric oxide (NO) and prostaglandin E2 (PGE2) production by suppressing inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) protein expression without affecting cell viability. We also demonstrated that the compounds reduced the secretion of pro-inflammatory cytokines such as tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6). Furthermore, compounds >1 and >2 inhibited LPS-induced nuclear factor-κB (NF-κB) activation by suppressing phosphorylation of IkappaB (IκB). These results indicated that the anti-inflammatory effects of these benzaldehyde derivatives in LPS-stimulated RAW264.7 macrophages were due to the inactivation of the NF-κB pathway. In addition, compounds >1 and >2 induced heme oxygenase-1 (HO-1) expression through the nuclear transcription factor-E2–related factor 2 (Nrf2) translocation. The inhibitory effects of compounds >1 and >2 on the production of pro-inflammatory mediators and on NF-κB binding activity were reversed by HO-1 inhibitor tin protoporphyrin (SnPP). Thus, the anti-inflammatory effects of compounds >1 and >2 also correlated with their ability of inducing HO-1 expression.