Sea mussel (Mytilus edulis) ethanol extract and its subfractions ameliorate AAPH-induced oxidative stress via the Keap1-Nrf2-ARE pathway

Abstract

Epidemiological evidence indicates that dietary antioxidants can mitigate oxidative stress and support immune regulation. The activation of nuclear factor erythroid 2-related factor 2 (Nrf2) represents a key cellular defense mechanism against oxidative damage. In this study, we investigated the protective effect of a sea mussel (Mytilus edulis) ethanol extract against 2,2'-Azobis(2-amidinopropane) dihydrochloride (AAPH)-induced cytotoxicity in HepG2 cells. The extract significantly attenuated cell damage and demonstrated a dose-dependent activation of the antioxidant response element (ARE). Mechanistically, the cytoprotection was mediated through the significant upregulation of multiple Nrf2-target genes at the transcriptional level, including HO-1, NQO1, GCLC, GCLM, GPx1, GR, and SOD1. Further analysis confirmed that the extract enhanced the protein expression of NQO1 and elevated intracellular GSH levels. Through bioactivity-guided fractionation, subfractions Fr. 5 and Fr. 6 were identified as the most active components, with Fr. 5 exhibiting the strongest ability to activate the Keap1-Nrf2-ARE pathway. These in vitro findings based on the HepG2 hepatocyte model indicate that sea mussel ethanol extract alleviates oxidative stress by directly scavenging radicals and by indirectly activating the endogenous Keap1-Nrf2-ARE antioxidant pathway, which provides fundamental cellular evidence supporting its further development as a promising nutraceutical candidate for follow-upin vivo investigations targeting oxidative stress-associated liver injury.

Keywords

Mytilus edulis / Nrf2 / Antioxidant response element / Oxidative stress / HepG2 cells

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