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•Out of seventy, six novel peptides were selected after microbial fermentation of brown rice.•Selected peptides demonstrated substantial in vitro radical scavenging activities.•CAA revealed the protective antioxidative potential of peptides against H2O2 oxidative damage.•P1, P4, and P5 showed higher protective antioxidant potential than standard ascorbic acid.•In in silico studies, all six peptides had a higher binding score to the Keap1-Kelch domain than TX6.
Oxidative stress is known to cause cell apoptosis, tissue damage, and pathological changes in the body, but antioxidant peptides are renowned radical scavengers. This study investigated the antioxidative and protective effect of six novel peptides obtained after microbial fermentation of brown rice. The selected peptides (MW ≤ 8 KDa), namely AVPYPQ (P1), ILTAV (P2), LGDVIGVP (P3), NPIFDYVLLP (P4), VAPFPEV (P5), and VLPVPK (P6) exhibited strong antioxidant potential against in vitro radicals with IC50 values for DPPH (5.12 ± 0.9–12.54 ± 0.6 µg/ml), ABTS (5.97 ± 0.2–14.20 ± 1.5 µg/ml), FRAP (4.98 ± 2.2–12.19 ± 0.8 µg/ml) and PSC (9.71 ± 0.5–17.84 ± 1.3 µg/ml),respectively. Additionally, these peptides reduced ROS concentrations in Caco-2 cells treated with hydrogen peroxide. In silico studies indicated all six peptides had a higher binding score for the Keap1-Kelch domain than TX6, a potential Keap1 reference ligand. These findings suggest peptides derived from fermented brown rice might be functional components in foods.