Marine Natural Product Honaucin A Attenuates Inflammation by Activating the Nrf2-ARE Pathway

Overview

Journal J Nat Prod

Date 2017 Dec 8

PMID 29215273

Citations 16

Authors

Samantha J Mascuch

Paul D Boudreau

Tristan M Carland

N Tessa Pierce

Joshua Olson

Mary E Hensler

Hyukjae Choi

Joseph Campanale

Amro Hamdoun

Victor Nizet

William H Gerwick

Teresa Gaasterland

Lena Gerwick

Affiliations

Soon will be listed here.

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.

Citing Articles

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