Protective Effect of Alpinia oxyphylla Fruit against tert -Butyl Hydroperoxide-Induced Toxicity in HepG2 Cells via Nrf2 Activation and Free Radical Scavenging and Its Active Molecules

• Published in: Antioxidants 2022-05, Vol.11 (5), p.1032
• Main Authors: Park, Chae Lee, Kim, Ji Hoon, Jeon, Je-Seung, Lee, Ju-Hee, Zhang, Kaixuan, Guo, Shuo, Lee, Do-Hyun, Gao, Eun Mei, Son, Rak Ho, Kim, Young-Mi, Park, Gyu Hwan, Kim, Chul Young
• Format: Article
• Language: English
• Subjects: Acetic acid; Alpinia oxyphylla; antioxidant activity; Antioxidants; Butyl hydroperoxide; Cell activation; Chromatography; Ethanol; Ethyl acetate; eudesma-3,11-dien-2-one; Free radicals; Heme; Heme oxygenase (decyclizing); n-Hexane; NMR; NRF2 protein; Nuclear magnetic resonance; Oxidative stress; Oxygenase; Proteins; Sesquiterpenes; Solvents; Toxicity; yakuchinone A
• ISSN: 2076-3921; 2076-3921
• DOI: 10.3390/ANTIOX11051032

Miq. (Zingiberaceae) extract exerts protective activity against -butyl hydroperoxide-induced toxicity in HepG2 cells, and the antioxidant response element (ARE) luciferase activity increased 6-fold at 30 μg/mL in HepG2 cells transiently transfected with ARE-luciferase. To identify active molecules, activity-guided isolation of the crude extract led to four sesquiterpenes ( , , , ) and two diarylheptanoids ( and ) from an -hexane extract and six sesquiterpenes ( - ) from an ethyl acetate extract. Chemical structures were elucidated by one-dimensional, two-dimensional nuclear magnetic resonance (1D-, 2D-NMR), and mass (MS) spectral data. Among the isolated compounds, eudesma-3,11-dien-2-one ( ) promoted the nuclear accumulation of nuclear factor (erythroid-derived 2)-like 2 (Nrf2) and increased the promoter property of the ARE. Diarylheptanoids, yakuchinone A ( ), and 5'-hydroxyl-yakuchinone A ( ) showed radical scavenging activity in 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 3-ethylbenzothiazoline-6-sulphonic acid (ABTS) assays. Furthermore, optimization of extraction solvents (ratios of water and ethanol) was performed by comparison of contents of active compounds, ARE-inducing activity, radical scavenging activity, and HepG2 cell protective activity. As a result, 75% ethanol was the best solvent for the extraction of fruit. This study demonstrated that exerted antioxidant effects via the Nrf2/HO-1 (heme oxygenase-1) pathway and radical scavenging along with active markers eudesma-3,11-dien-2-one ( ) and yakuchinone A ( ).