Abstract
Various dietary phytochemicals seem to display antioxidant activity through the NF-E2-related factor 2 (Nrf2) pathway. However, few studies have demonstrated its antioxidant effect and Nrf2 dependency at the animal level. We constructed a zebrafish-based assay system to analyze the in vivo antioxidant activity of phytochemicals and examined the activity of 10 phytochemicals derived from spices, using this system as a pilot study. Hydrogen peroxide and arsenite were used as oxidative stressors, and Nrf2 dependency was genetically analyzed using an Nrf2-mutant zebrafish line. The activities of curcumin, diallyl trisulfide and quercetin were involved in the reduction of hydrogen peroxide toxicity, while those of cinnamaldehyde, isoeugenol and 6-(methylsulfinyl)hexyl isothiocyanate were involved in the reduction of arsenite toxicity. The antioxidant activities of these phytochemicals were all Nrf2 dependent, with the exception of cinnamaldehyde, which showed strong antioxidant effects even in Nrf2-mutant zebrafish. In summary, we succeeded in constructing an assay system to evaluate the in vivo antioxidant activity of various phytochemicals using zebrafish larvae. Using this system, we found that each spice-derived phytochemical has its own specific property and mechanism of antioxidant action.
Highlights
Oxidative stress has various harmful effects in animal cells and leads to serious diseases and accelerates the aging process [1,2]
We evaluated the antioxidant activity of 10 spice-derived phytochemicals (capsaicin, carnosic acid, cinnamaldehyde, curcumin, diallyl trisulfide, eugenol, 6-gingerol, isoeugenol, 6-(methylsulfinyl)hexyl isothiocyanate (6-MSITC) and quercetin) and analyzed their NF-E2-related factor 2 (Nrf2) dependency using wild-type and Nrf2-mutant zebrafish
We have been evaluating the antioxidant activity of Nrf2-activating compounds based on the improvement of the survival rate of zebrafish larvae exposed to toxic oxidative stress [15,27,28]
Summary
Oxidative stress has various harmful effects in animal cells and leads to serious diseases and accelerates the aging process [1,2]. One effective and economical strategy for reducing oxidative stress in the body is to consume antioxidant phytochemicals that are included in various foods, such as curcumin, quercetin and sulforaphane [4,5]. These dietary phytochemicals are considered to activate and/or induce several antioxidant proteins in host cells, mainly via the NF-E2-related factor 2 (Nrf2) pathway [6,7]. A number of phytochemicals that have been reported to activate the Nrf pathway are expected to prevent lifestyle-related diseases and extend healthy life expectancy in humans [11]. Sulforaphane is a promising agent that is under preclinical evaluation in many models of disease prevention [13]
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