Secondary metabolites from marine sources as inhibitors of advanced glycation end products (AGEs) and collagenase

Advanced glycation end products (AGEs) have recently received particular attention in aging research, and especially the extracellular matrix (ECM) proteins have been regarded as one of the major target structures for glycation. Collagen, the major component of ECM, which is important for mechanical stability and cell-interaction, loses its function during glycation leading to stiffness, decreased flexibility and impairment in tissue turnover [1]. Some natural products have already been identified as AGEs inhibitors, however connected to diabetes and other degenerative diseases but still poorly studied in skin aging. Marine species have received great attention as sources for natural photoprotective agents and unique biomolecules, which are often a result of adaptation strategies to the extreme marine environment [2]. Therefore, our study focused on secondary metabolites from various marine sources including mycosporine-like amino acids (MAAs) from Rhodophyta, coumarins from Chlorophyta, and sulfated flavones from seagrasses that were isolated by using various chromatographic techniques. Their structures were determined by nuclear magnetic resonance and mass spectrometry, and the compounds tested in two different fluorescence based in vitro assays to investigate their collagenase and pentosidine-like AGEs inhibitory effects. In total, 24 substances were investigated mostly showing comparable IC₅₀ values in both assays. For example, IC₅₀ values around 75-150 µM were determined for the MAAs. Interestingly, the sulfated flavones from Zostera marina exhibited higher activities than their non-sulfated equivalent, e.g luteolin-7,3ʹ-disulfate showing an IC₅₀ of of 60 µM compared to luteolin with 0.4 mM. Some substances showed even higher activities than the standard inhibitor rutin.

• References

• 1 Gkogkolou P, Böhm M. Advanced glycation end products. Key players in skin aging? Dermatoendocrinol 2012; 3: 259-70.
• 2 Núñez-Pons L, Avila C, Romano G, Verde C, Giordano D. UV Protective Compounds in Marine Organisms from the Southern Ocean. Mar Drugs 2018; 16: 336-391.