mycosporine-2-glycine and Inflammation

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 H

Topics: Animals; Anti-Inflammatory Agents; Antioxidants; Cell Survival; Cyclohexanols; Glycine; Inflammation; Lipopolysaccharides; Macrophages; Mice; RAW 264.7 Cells; Signal Transduction; Structure-Activity Relationship

Certain photosynthetic marine organisms have evolved mechanisms to counteract UV-radiation by synthesizing UV-absorbing compounds, such as mycosporine-like amino acids (MAAs). In this study, MAAs were separated from the extracts of marine green alga Chlamydomonas hedleyi using HPLC and were identified as porphyra-334, shinorine, and mycosporine-glycine (mycosporine-Gly), based on their retention times and maximum absorption wavelengths. Furthermore, their structures were confirmed by triple quadrupole MS/MS. Their roles as UV-absorbing compounds were investigated in the human fibroblast cell line HaCaT by analyzing the expression levels of genes associated with antioxidant activity, inflammation, and skin aging in response to UV irradiation. The mycosporine-Gly extract, but not the other MAAs, had strong antioxidant activity in the 2,2-diphenyl-1-picryhydrazyl (DPPH) assay. Furthermore, treatment with mycosporine-Gly resulted in a significant decrease in COX-2 mRNA levels, which are typically increased in response to inflammation in the skin, in a concentration-dependent manner. Additionally, in the presence of MAAs, the UV-suppressed genes, procollagen C proteinase enhancer (PCOLCE) and elastin, which are related to skin aging, had increased expression levels equal to those in UV-mock treated cells. Interestingly, the increased expression of involucrin after UV exposure was suppressed by treatment with the MAAs mycosporine-Gly and shinorine, but not porphyra-334. This is the first report investigating the biological activities of microalgae-derived MAAs in human cells.

Topics: Amino Acids; Anti-Inflammatory Agents; Cell Line; Chlamydomonas; Chlorophyta; Cyclohexanols; Cyclohexanones; Cyclohexylamines; Cyclooxygenase 2; Elastin; Extracellular Matrix Proteins; Fibroblasts; Glycine; Glycoproteins; Humans; Inflammation; Skin; Skin Aging; Ultraviolet Rays