J Appl Biomed 16:75-80, 2018 | DOI: 10.1016/j.jab.2017.11.006

Apigenin inhibits ethanol-induced oxidative stress and LPS-induced inflammatory cytokine production in cultured rat hepatocytes

Feng Wang^a, Rui-Jun Zhou^a, Xi Zhao^a,b, Hua Ye^c, Mei-Lin Xie^a,*

^a Soochow University, College of Pharmaceutical Sciences, Department of Pharmacology, Suzhou, Jiangsu Province, China

^b Nantong University, School of Pharmacy, Department of Pharmaceutical Laboratory, Nantong, Jiangsu Province, China

^c Leiyunshang Pharmaceutical Co., Ltd., Suzhou, Jiangsu Province, China

Apigenin is a natural flavonoid compound that has antioxidative, anti-inflammatory, and hepatoprotective effects, but the underlying mechanisms are still unclear. In this study, the effects of apigenin on ethanol-induced oxidative stress and lipopolysaccharide (LPS)-induced inflammatory cytokine production were examined in cultured rat hepatocytes. Following pretreatment of ethanol-stimulated hepatocytes with apigenin 6-24 mM for 2 h, the levels of cytochrome P450 2E1 (CYP2E1) protein expression and supernatant alanine aminotransferase and malondialdehyde were reduced (P < 0.05 or P < 0.01), while the activities of glutathione reductase and glutathione peroxidase were increased (P < 0.05 or P < 0.01). Likewise, the pretreatment of LPS-stimulated hepatocytes with the same concentrations of apigenin could decrease the levels of nuclear factor-κB protein expression and supernatant tumor necrosis factor-α and interleukin-6 (P < 0.05 or P < 0.01), and increase the level of IκB-α protein expression (P < 0.05 or P < 0.01). In all of these results, the concentration of 24 μM was the most effective. These findings demonstrate that apigenin may exert an inhibitory effect on ethanol-induced oxidative stress and LPS-induced inflammation in the cultured hepatocytes, and its mechanisms may be related to the reduction of CYP2E1 expression, increment of antioxidative ability, and regulation of inflammatory gene expression.

Keywords: Apigenin; CYP2E1; Hepatocytes; Inflammatory cytokines; Oxidative stress

Received: April 24, 2017; Revised: July 31, 2017; Accepted: November 24, 2017; Published: February 1, 2018  Show citation