Semisynthetic quercetin-quinone mitigates BV-2 microglia activation through modulation of Nrf2 pathway.

Free Radical Biology & Medicine
Martin ŠkandíkLucia Rackova

Abstract

During brain ageing, microglia, the resident immune cells of the CNS, are immunologically activated and contribute to neuroinflammation, a vicious cycle that supports development of neurological disorders. Therapeutic approaches focus mainly on downregulation of their pro-inflammatory activated state that is associated with health benefits. Electrophilic compounds, such as natural quinones and their reduced pro-electrophilic precursors, flavonoids, represent a wide group of diverse substances with important biological effects. They can cause considerable cytotoxicity when used at higher dosages, but on the other hand, they have versatile health benefits at lower dosages. In this study, we investigated the cytotoxicity and prooxidant profile of synthetic conjugate of two electrophilic compounds, quercetin and 1,4-naphthoquinone, 4'-O-(2-chloro-1,4-naphthoquinone-3-yloxy) quercetin (CHNQ), and its attenuation of inflammatory responses and modulation of Nrf2 pathway in BV-2 microglial cells. CHNQ showed higher cytotoxicity than its precursors, accompanied by promotion of production of reactive oxygen species along with G2/M cell cycle arrest at higher concentrations tested. Nevertheless, at a lower non-toxic concentration, CHNQ, m...Continue Reading

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