Genistein-7-O-octanoate, a lipophilized genistein, exhibits antioxidant activity through activating the Nrf2 signaling pathway in Caco-2 cells

Abstract

Genistein was esterified with nine acyl chlorides. The resulting esters were characterized using HPLC-MS and 1H and 13C NMR. The antioxidant activity of genistein esters was assessed in both chemical models and Caco-2 cells. All genistein esters exhibited lower 1,1-Diphenyl-2-picrylhydrazyl radical 2,2-Diphenyl-1-(2,4,6-trinitrophenyl) hydrazyl (DPPH) and 2, 2′-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radical scavenging activities compared to genistein. Seven genistein monoesters exhibited stronger cellular antioxidant activity (CAA) than genistein (CAA unit = 1.1), with genistein-7-O-octanoate (G-C8:0) (CAA unit = 25.9) being the strongest. Further mechanism study revealed that G-C8:0 treatment significantly enhanced the activities of antioxidative enzymes such as superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-PX), along with upregulating the protein expression of nuclear factor E2-related factor (Nrf2) and its downstream antioxidases, including SOD, Heme oxygenase 1 (HO-1), and GSH-PX. Overall, these findings indicate that esterification is a promising method for augmenting the cellular antioxidant activity of parent isoflavones.

Keywords

• Genistein
• Esterification
• Antioxidant mechanism
• Nrf2
• Caco-2