2'-Hydroxychalcone Induced Cytotoxicity via Oxidative Stress in the Lipid-Loaded Hepg2 Cells

Yun Qian; Yang Yang; Kai Wang; Wenjun Zhou; Yanqi Dang; Mingzhe Zhu; Fenghua Li; Guang Ji

doi:10.3389/fphar.2019.01390

2'-Hydroxychalcone Induced Cytotoxicity via Oxidative Stress in the Lipid-Loaded Hepg2 Cells

Front Pharmacol. 2019 Nov 20:10:1390. doi: 10.3389/fphar.2019.01390. eCollection 2019.

Authors

Yun Qian^{1

2}, Yang Yang², Kai Wang², Wenjun Zhou¹, Yanqi Dang¹, Mingzhe Zhu³, Fenghua Li², Guang Ji¹

Affiliations

¹ Institute of Digestive Diseases, Longhua Hospital, China-Canada Center of Research for Digestive Diseases (ccCRDD), Shanghai University of Traditional Chinese Medicine, Shanghai, China.
² Experiment Center for Science and Technology, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
³ School of Public Health, Shanghai University of Traditional Chinese Medicine, Shanghai, China.

Abstract

Licorice is a common herb used in traditional Chinese medicine, and has been widely used clinically. Physiologically, although it is relatively safe, licorice-induced hepatotoxicity in the presence of other diseases needs to be evaluated. The present study was conducted to investigate the toxicological effects of the bioactive components of licorice in HepG2 cells cultured with or without free fatty acid (FFA). The compounds, isoliquiritigenin, licorice chalcone A, bavachalcone, and 2'-hydroxy chalcone (2'-HC) inhibited cell proliferation at certain concentrations in lipid loaded cells with limited effects on the normal cells. The representative compound 2'-HC (at a concentration of ≥ 20µM) increased the oxygen consumption rate, ATP production, mitochondrial membrane potential, generation of total and mitochondrial reactive oxygen species (ROS) production, and expression of inflammatory cytokines (TNF-α, IL-6, and IL-8) and Caspase-9 protein; and reduced the expression of SOD1. In addition, we found exaggerated lipid accumulation in HepG2 cells treated with FFA. Our results suggest that 2'-HC at a concentration of ≥ 20µM might cause damage to the hepatocytes. The toxicity may be related to excess ROS production and inadequate SOD1 expression, leading to apoptosis, inflammation, and cellular dysfunctions.

Keywords: 2′-hydroxychalcone; cytotoxicity; hepatocyte; licorice; reactive oxygen species.