Viridicatol from Marine-derived Fungal Strain Penicillium sp. SF-5295 Exerts Anti-inflammatory Effects through Inhibiting NF-kappaB Signaling Pathway on Lipopolysaccharide-induced RAW264.7 and BV2 Cells

ABSTRACT

Viridicatol (1) has previously been isolated from the extract of the marine-derived fungus Penicillium sp. SF-5295. In the course of further biological evaluation of this quinolone alkaloid, anti-inflammatory effect of 1 in RAW264.7 and BV2 cells stimulated with lipopolysaccharide (LPS) was observed. In this study, our data indicated that 1 suppressed the expression of well-known pro-inflammatory mediators such as inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2, and consequently inhibited the production of iNOS-derived nitric oxide (NO) and COX-2-derived prostaglandin E2 (PGE2) in LPS stimulated RAW264.7 and BV2 cells. Compound 1 also reduced mRNA expression of pro-inflammatory cytokines such as interleukin-1beta (IL-1beta), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-alpha). In the further evaluation of the mechanisms of these anti-inflammatory effects, 1 was shown to inhibit nuclear factor-kappa B (NF-kappaB) pathway in LPS-stimulated RAW264.7 and BV2 cells. Compound 1 blocked the phosphorylation and degradation of inhibitor kappa B (IkappaB)-alpha in the cytoplasm, and suppressed the translocation of NF-kappaB p65 and p50 heterodimer in nucleus. In addition, viridicatol (1) attenuated the DNA-binding activity of NF-kappaB in LPS-stimulated RAW264.7 and BV2 cells.