Whole-Grain Oryza sativa L. Flour Extract Exhibits Potent Antioxidant and Anti-Inflammatory Activity in Rats with Experimentally Induced Inflammation

Whole-grain rice (<i>Oryza sativa</i> L.) is a rich source of polyphenols. The <i>in vivo</i> mechanisms linking its phytochemical profile to antioxidant and anti-inflammatory effects remain incompletely defined. This study investigated the antioxidant and anti-inflammatory activity of a whole-grain rice flour 70% ethanol extract (OSEE) and correlated these effects with its phenolic composition. OSEE showed high total phenolic content 0.121 ± 0.002 mg GAE/g d.w.), a lower total flavonoid content (61.83 ± 4.03 µg QE/g d.w.), and a phenolic profile dominated by phenolic acids (~87%), with ferulic and protocatechuic acids among the most abundant constituents. OSEE displayed significant <i>in vitro</i> antioxidant activity in DPPH, FRAP, hydrogen peroxide, and nitric oxide scavenging assays. <i>In vivo</i> activity was evaluated in male Wistar rats with turpentine oil-induced acute inflammation using both therapeutic (post-induction) and prophylactic (pre-induction) protocols, testing three oral doses of lyophilized extract (1.0, 0.50, and 0.25 g/kg/day). <i>In vivo</i>, OSEE attenuated systemic oxidative stress (TOS, TAC, OSI, AOPP, MDA, NOx, 3-nitrotyrosine, total thiols) and the expression of pro-inflammatory markers (NF-κB p65, IL-1β, IL-18, caspase-1) in a dose-dependent manner with both protocols, with the highest dose producing the most consistent reductions, while the expression level of the anti-inflammatory factor IL-10 remained unchanged. PCA supported a shift in biomarker networks toward a non-inflamed profile. These findings indicate that OSEE exerts coordinated antioxidant and anti-inflammatory effects <i>in vivo</i> that are strongly associated with its phenolic composition.