In this study, Tartary buckwheat was fermented by Monascus purpureus, and the fermented Tartary buckwheat oil (FTBO) was extracted under supercritical CO2 conditions. γ-Oryzanol, fatty acids, antioxidant capacities, and non-target metabolomics were investigated, and the lipid-lowering and immune effects of FTBO on high-fat mice were evaluated. The results showed that γ-oryzanol content reached 27.09 mg/g; oleic acid content increased by 12.56%; FTBO improved the antioxidant capacities of DPPH, ABTS, and Hydroxyl compared with raw Tartary buckwheat oil (TBO); and 207 metabolites were identified, including carboxylic acids and its derivatives and fatty acyls. FTBO gavage in high-fat mice had a dose effect. Three dose groups reduced TC, TG, and LDL-C levels in the liver and plasma and increased HDL-C level in the liver. Among them, the high-dose group exhibited the most significant effect on reducing inflammatory factors of ET, TNF-α, IL-1β, and IL-6 in the liver, which were 18.85, 570.12, 50.47, and 26.22 pg/mL, respectively (p ˂ 0.05). Liver damage in mice was also effectively ameliorated. Therefore, fermented Tartary buckwheat by M. purpureus is an effective method to enhance its biological activity. FTBO can be used as a functional product to lower blood lipids and modulate immune activity.
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