Hyperoside and quercetin are similar in molecular structures. In this study, the antioxidant regulatory targets of hyperoside and quercetin are mainly in the Nrf2 pathway predicted by network pharmacology. And the antioxidant effect and mechanism of hyperoside and quercetin were measured and compared in H₂O₂-induced HepG2 cells and Caenorhabditis elegans. The findings indicated that quercetin was more effective than hyperoside in reducing oxidative damage, which was proved by improved cell viability, decreased reactive oxygen species (ROS) production, decreased cellular apoptosis, and alleviated mitochondrial damage. In addition, quercetin was more efficient than hyperoside in enhancing the expression of nuclear factor (erythroid-2-derived)-related factor 2 (Nrf2)-associated mRNAs, increasing the activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase (CAT), and reducing the cellular malondialdehyde (MDA) content. Quercetin was superior to hyperoside in prolonging the lifespan of worms, decreasing the accumulation of lipofuscin, inhibiting ROS production, and increasing the proportion of skn-1 in the nucleus. With the Nrf2 inhibitor ML385, we verified that quercetin and hyperoside primarily protected the cells against oxidative damage via the Nrf2 signalling pathway. Furthermore, molecular docking and dynamics simulations demonstrated that the quercetin- Kelch-like ECH-associated protein 1 (Keap1) complex was more stable than the hyperoside-Keap1 complex. The stable structure of the complex might hinder the binding of Nrf2 and Keap1 to release Nrf2 and facilitate its entry into the nucleus to play an antioxidant role. Overall, quercetin had a better antioxidant than hyperoside.

Pinocembrin is a natural flavonoid compound which is capable of antioxidant, antibacterial, anti-inflammatory, and antineoplastic activities. The present study aimed to enhance the solubility and antioxidant activities of pinocembrin by complex formation with lecithin. The physicochemical characteristics of pinocembrin–lecithin complex were analyzed by ultraviolet (UV), fourier-transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), differential scanning calorimetry (DSC), and solubility assay, and the antioxidant activities of pinocembrin–lecithin complex were evaluated via radical scavenging capacities for 2,2′-diphenyl-1-picrylhydrazyl (DPPH), 2,2′-azino-bis(3-ethylbenzthiazoline-6-sulphonic acid) (ABTS), hydroxyl, and superoxide-anion. The results indicated that pinocembrin complex with lecithin could significantly improve the solubility of pinocembrin in water and n-octane, the pinocembrin–lecithin complex displayed no characteristic endothermic peak and the appearance of amorphous state, compared to the pinocembrin, and no new covalent bond was produced in the pinocembrin and lecithin compound. It was demonstrated that the antioxidant activities of pinocembrin were obviously enhanced by the complex with lecithin, and the scavenging capacities for hydroxyl radical, DPPH, superoxide-anion radical, and ABTS radical of pinocembrin–lecithin complex were 82.44 ± 2.21%, 40.07 ± 1.32%, 59.15 ± 0.86%, and 24.73 ± 1.04% at 1.0 mg/mL, respectively. It suggested that the pinocembrin–lecithin complex had a great potential application prospect in the healthcare industry and in clinical practice.

Hawthorn fruit extract (HFE) protects PC12 cells against oxidative damage induced by H ₂ O ₂ in vitro , and prolongs the lifespan of Caenorhabditis elegans via IIS signaling pathway in vivo .