Title: Marine Natural Product Honaucin A Attenuates Inflammation by Activating the Nrf2-ARE Pathway.
Authors: Mascuch, Samantha J; Boudreau, Paul D; Carland, Tristan M; Pierce, N Tessa; Olson, Joshua; Hensler, Mary E; Choi, Hyukjae; Campanale, Joseph; Hamdoun, Amro; Nizet, Victor; Gerwick, William H; Gaasterland, Teresa; Gerwick, Lena
Published In J Nat Prod, (2018 03 23)
Abstract: The cyanobacterial marine natural product honaucin A inhibits mammalian innate inflammation in vitro and in vivo. To decipher its mechanism of action, RNA sequencing was used to evaluate differences in gene expression of cultured macrophages following honaucin A treatment. This analysis led to the hypothesis that honaucin A exerts its anti-inflammatory activity through activation of the cytoprotective nuclear erythroid 2-related factor 2 (Nrf2)-antioxidant response element/electrophile response element (ARE/EpRE) signaling pathway. Activation of this pathway by honaucin A in cultured human MCF7 cells was confirmed using an Nrf2 luciferase reporter assay. In vitro alkylation experiments with the natural product and N-acetyl-l-cysteine suggest that honaucin A activates this pathway through covalent interaction with the sulfhydryl residues of the cytosolic repressor protein Keap1. Honaucin A presents a potential therapeutic lead for diseases with an inflammatory component modulated by Nrf2-ARE.
PubMed ID: 29215273
MeSH Terms: Alkylation/drug effects; Animals; Anti-Inflammatory Agents/chemistry; Anti-Inflammatory Agents/pharmacology*; Antioxidants/metabolism; Aquatic Organisms/chemistry*; Biological Products/chemistry; Biological Products/pharmacology*; Cell Line; Cell Line, Tumor; Cytoprotection/drug effects; Female; Humans; Inflammation/drug therapy*; Inflammation/metabolism; Kelch-Like ECH-Associated Protein 1/metabolism; MCF-7 Cells; Mice; NF-E2-Related Factor 2/metabolism*; RAW 264.7 Cells; Signal Transduction/drug effects*