Anti‐Inflammatory Effects of New Naphthyridine from Sponge Aaptos suberitoides in LPS‐Stimulated RAW 264.7 Macrophages via Regulation of MAPK and Nrf2 Signaling Pathways

Abstract

AbstractTwo new naphthyridine compounds, 4‐methoxycarbonyl‐5‐oxo‐1,6‐naphthyridine (1) and 5‐methoxycarbonyl‐4‐oxo‐1,6‐naphthyridine (2) were obtained from the MeOH extracts of sponge Aaptos suberitoides. Their structures were determined by spectroscopic methods, including HR‐ESI‐MS, 1D‐NMR (1H‐NMR, 13C‐NMR), 2D‐NMR (COSY, HSQC, HMBC). The structure of compound 1 was further confirmed via single crystal X‐ray diffraction analysis. Compound 1 was found to reduce NO production in LPS‐induced RAW 264.7 macrophages with IC50 value of 0.15 mM. In addition, it decreased the mRNA expression levels of pro‐inflammatory mediators, such as the tumor necrosis factor‐α (TNF‐α), interleukin‐6 (IL‐6), interleukin‐1β (IL‐1β), inducible nitric oxide synthase (iNOS) and cyclooxygenase‐2 (COX2) in LPS‐induced macrophages. It also decreased the protein expression of iNOS and COX‐2 in LPS‐induced macrophages. Mechanistic studies further revealed that compound 1 inhibited the mitogen‐activated protein kinase (MAPK), and activated the nuclear factor erythroid 2‐related factor 2/heme oxygenase‐1 (Nrf2/HO‐1) signaling pathways in LPS‐induced RAW 264.7 macrophages.