Oxidative stress, caused by the excessive production of reactive oxygen species (ROS), results in cellular damage. Therefore, functional materials with antioxidant properties are necessary to maintain redox balance. Turmeric leaves (Curcuma longa L. leaves; TL) are known to have antioxidant properties, including 2,2-Diphenyl-1-picrylhydrazyl (DPPH), 2,2′-Azino-di-(3-ethylbenzothiazoline)-6-sulfonic acid (ABTS), and Hydrogen peroxide (H₂O₂) radical scavenging activity in several studies. The antioxidant effects of TL come from distinct bioactive compounds, such as curcumin, total phenolic compounds, and flavonoids. Therefore, in this study, the antioxidant effects of a water extract of TL (TLE) against H₂O₂ treatment were assessed in vitro Vero cells and in vivo zebrafish models. The intracellular ROS generation and the proportion of sub-G1 phase cells were evaluated in H₂O₂- or/and TLE-treated Vero cells to measure the antioxidant activity of TLE. TLE showed outstanding intracellular ROS scavenging activity and significantly decreased the proportion of cells in the sub-G1 phase in a dose-dependent manner. Furthermore, cell death, ROS generation, and lipid peroxidation in the H₂O₂-treated zebrafish model were attenuated as a consequence of TLE treatment. Collectively, the results from this study suggested that TLE may be an alternative material to relieve ROS generation through its antioxidant properties or a suitable material for the application in a functional food industry.

The aim of this study was to improve the anti-inflammatory activities of apigenin through co-treatment with resveratrol as a bioenhancer of apigenin. RAW 264.7 cells pretreated with hepatic metabolites formed by the co-metabolism of apigenin and resveratrol (ARMs) in HepG2 cells were stimulated with lipopolysaccharide (LPS). ARMs prominently inhibited (p < 0.05) the production of nitric oxide (NO), prostaglandin E₂ (PGE₂), interleukin (IL)-1β, IL-6 and TNF-α. Otherwise no such activity was observed by hepatic metabolites of apigenin alone (AMs). ARMs also effectively suppressed protein expressions of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). Co-administration of apigenin (50 mg/kg) and resveratrol (25 mg/kg) also showed a significant reduction of carrageenan-induced paw edema in mice (61.20% to 23.81%). Co-administration of apigenin and resveratrol led to a 2.39 fold increase in plasma apigenin levels compared to administration of apigenin alone, suggesting that co-administration of resveratrol could increase bioavailability of apigenin. When the action of resveratrol on the main apigenin metabolizing enzymes, UDP-glucuronosyltransferases (UGTs), was investigated, resveratrol mainly inhibited the formation of apigenin glucuronides by UGT1A9 in a non-competitive manner with a K_i value of 7.782 μM. These results suggested that resveratrol helps apigenin to bypass hepatic metabolism and maintain apigenin’s anti-inflammatory activities in the body.

The glyoxal-lysine dimer (GOLD), which is a glyoxal (GO)-derived advanced glycation end product (AGE), is produced by the glycation reaction. In this study, we evaluated the effect of GOLD on the oxidative damage and inflammatory response in SV40 MES 13 mesangial cells. GOLD significantly increased the linkage with the V-type immunoglobulin domain of RAGE, a specific receptor of AGE. We found that GOLD treatment increased RAGE expression and reactive oxygen species (ROS) production in mesangial cells. GOLD remarkably regulated the protein and mRNA expression of nuclear factor erythroid 2-related factor 2 (NRF2) and glyoxalase 1 (GLO1). In addition, mitochondrial deterioration and inflammation occurred via GOLD-induced oxidative stress in mesangial cells. GOLD regulated the mitogen-activated protein kinase (MAPK) and the release of proinflammatory cytokines associated with the inflammatory mechanism of mesangial cells. Furthermore, oxidative stress and inflammatory responses triggered by GOLD were suppressed through RAGE inhibition using RAGE siRNA. These results demonstrate that the interaction of GOLD and RAGE plays an important role in the function of mesangial cells.