Mycosporine-2-glycine exerts anti-inflammatory and antioxidant effects in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages

Abstract

Mycosporine-like amino acids (MAAs) are a group of water-soluble low-molecular-weight secondary metabolites, which are well-documented UV-screening molecules and antioxidants. We have recently demonstrated that a rare MAA, mycosporine-2-glycine (M2G), efficiently inhibited the formation of advanced glycation end-products (AGEs). Because AGEs contribute significantly to the aging process, including the pathogenesis and progression of age-related diseases, the present study further evaluated anti-inflammatory effects of M2G using an in vitro model of RAW 264.7 macrophages. We measured the inflammatory signaling molecule nitric oxide (NO) under inflammatory stimulation by lipopolysaccharide (LPS), revealing that M2G diminished LPS-induced NO production. M2G inhibited NO production approximately 2-3-fold more potently than other MAAs, including shinorine, porphyra-334, and palythine. Transcriptional analyses revealed that M2G significantly suppressed iNOS and COX-2 expression. Therefore, M2G inhibits the production of inflammatory mediators by suppressing the NF-κB pathway. Furthermore, under H₂O₂-induced oxidative stress, M2G down-regulated Sod1, Cat, and Nrf2 expression. Our findings clearly demonstrate anti-inflammatory and antioxidant effects of M2G in LPS-stimulated RAW 264.7 macrophages. Structure-activity relationships of biologically active MAAs are also discussed.