Stimulation of Activity and Expression of Antioxidant Enzymes by Solvent Fractions and Isolated Compound from Cedrela sinensis Leaves in HepG2 Cells

Abstract

Cedrela sinensis has been widely used in traditional Oriental medicine to treat a variety of diseases. However, little is known about the cellular actions by which this plant mediates its antioxidant effects. In this study, activity-guided fractionations of C. sinensis leaves were performed using column chromatographic techniques as well as biological assays with HepG2 cells. The ethanol (95%) extract of C. sinensis leaves was sequentially extracted with hexane, chloroform, ethyl acetate (EtOAc), butanol, and water, and the fractions were screened for their antioxidant potentials for scavenging radicals as well as inducing antioxidant enzyme activity and expression. The most potent antioxidant EtOAc fraction was further separated using chromatographic techniques including open column and high-performance liquid chromatography. Compound 1 from the EtOAc fraction showed strong radical scavenging activity with a 50% scavenging concentration value close to that of ascorbic acid and induced both the activity and expressions of antioxidant enzymes such as superoxide dismutase, catalase, and glutathione peroxidase. Inhibitory effects on the phosphorylations of upstream mitogen-activated protein kinases such as c-Jun N-terminal kinase, extracellular signal-regulated kinase, and p38 were also observed after treatments with compound 1. Compound 1 was identified as quercitrin by ¹H- and ¹³C-nuclear magnetic resonance techniques. Taken together, our findings demonstrated for the first time that C. sinensis leaves appear to be a useful source of a cytoprotective and chemopreventive agent that can stimulate the activity and expression of crucial antioxidant enzymes in cells.