New Utilization of <i>Fraxinus mandshurica</i> Leaves: As a Safe and Promising Natural Antioxidant

In this paper, an in-depth study on <i>Fraxinus mandshurica</i> (FM) was conducted, focusing on the chemical constituents, in vitro and in vivo antioxidant activities of flavonoids, acute oral toxicity testing, network pharmacology, and molecular docking in the leaves of FM. The in vitro antioxidant results revealed that the total flavonoid extract (TFE), kaempferol, quercetin, and rutin exhibited similar antioxidant activities, with TFE demonstrating significantly better scavenging ability against hydroxyl radical compared to the other flavonoids. Moreover, in vivo antioxidant findings indicated that TFE led to a significant increase in glutathione peroxidase and superoxide dismutase activities along with a decrease in malondialdehyde levels in the liver tissues of mice in an ethanol-induced oxidative stress model, outperforming quercetin. The acute oral toxicity test established 5000 mg/kg of bw as the LD₅₀ for TFE in rats. Through network pharmacological analysis, it was observed that all seven flavonoids in FM exhibited spontaneous binding to their respective key targets, reinforcing their potential antioxidant properties. Consequently, based on the experimental outcomes, TFE appears to be a safe and promising antioxidant source, indicating its potential as a new natural antioxidant resource.