FOXO3a Activation by oxyresveratrol ofMorus bombyciskoidzumi extract mediates antioxidant activity

Abstract

Although Morus bombycis koidzumi (MB) extract has been reported to have antioxidant activity, the mechanism underlying its antioxidant activity has not been elucidated. In this report, we showed that FOXO3a was activated by MB extract. FOXO3a is a transcription factor that is involved in various biological functions such as cell cycle control, apoptosis, DNA repair, and reactive oxygen species (ROS) detoxification. Protein levels of FOXO3a and MnSOD, target gene of FOXO3a were increased by the MB extract. The ROS level was decreased by the MB extract in human embryonic fibroblast (HEF) cells. Among components of the MB extract, oxyresveratrol (2 ′ ,4 ′ ,3,5-tetrahydroxystilbene) was identified and turned out to activate FOXO3a. The protein level of FOXO3a was increased by oxyresveratrol. Promoter activities of target genes of FOXO3a such as MnSOD, p27, and GADD45 were activated by oxyresveratrol. The ROS level was decreased by oxyresveratrol in HEF cells in a dose-dependent manner. However, the ROS level was elevated in HEF cells when FOXO3a was knocked down by si-FOXO3a, while overexpression of wt-FOXO3a decreased the cellular ROS level, indicating that antioxidant activity by oxyresveratrol is FOXO3a-dependent. These results indicate that oxyresveratrol of MB extract mediates an antioxidant activity through upregulation of MnSOD by FOXO3a activation. ARTICLE HISTORY

Oxyresveratrol: Sources, Productions, Biological Activities, Pharmacokinetics, and Delivery Systems

“…FOXO3a (Forkhead box O3) is a transcription factor known to be important in several biological functions, such as DNA repair and detoxification of ROS. ORV was shown to suppress the ROS level in human embryonic fibroblast (HEF) cells by upregulating Manganese superoxide dismutase (MnSOD) through the activation of FOXO3a [ 175 ].…”

IL2 is required for functional maturation of regulatory T cells

“…FACS-sorted cells were cultured in complete RPMI-1640 medium (WelGENE, Daegu, Korea), supplemented with 10% fetal bovine serum (WelGENE), penicillin, streptomycin (Sigma-Aldrich, St. Louis, MO, USA), L-glutamine (2 mM; Life Technologies, Carlsbad, CA, USA), sodium pyruvate (2 mM; Sigma-Aldrich), nonessential amino acid (0.1 mM; Sigma-Aldrich) and 2-ME (50 μM; Sigma-Aldrich) (Heo et al 2016).…”

Oxyresveratrol induces apoptosis and inhibits cell viability via inhibition of the STAT3 signaling pathway in Saos‑2 cells

“…as a natural ingredient, which is primarily found in Morus alba l., oxyresveratrol (oreS) has extensive biological effects. over the previous two decades, oreS has been reported as a powerful tyrosinase activity inhibitor (22,23), and also as having antioxidative (24,25), anti-inflammatory (26,27), anticancer (28)(29)(30) and anti-lipogenesis properties (31). oreS has also been observed to exert strong neuroprotective effects, as it reduces neuronal oxidative damage (32,33).…”