Anti-Inflammatory and PPAR Transactivational Properties of Flavonoids from the Roots of Sophora flavescens

Anti-inflammatory and peroxisome proliferator-activated receptors (PPARs) transactivational effects of nine compounds (1-9) from the roots of Sophora flavescens were evaluated using NF-B-luciferase, reverse transcriptase polymerase chain reaction, peroxisome proliferator response element (PPRE)-luciferase, and GAL-4-PPAR chimera assays. Compounds 4 and 8 significantly inhibited TNF-induced NF-B transcriptional activity in HepG2 cells in a dose-dependent manner, with IC50 values of 4.0 and 4.4M, respectively. Furthermore, the transcriptional inhibitory function of these compounds was confirmed by a decrease in cyclooxgenase 2 and inducible nitric oxide synthase gene expression levels in HepG2 cells. Compounds 1, 3, 5, 6, 8, and 9 significantly activated the transcription of PPARs in a dose-dependent manner, with EC50 values ranging from 1.1 to 13.0M. Compounds 1, 3, 5, 6, 8, and 9 exhibited dose-dependent PPAR transactivational activity, with EC50 values in a range of 0.9-16.0M. Compounds 1, 3, 8, and 9 also significantly upregulated PPAR activity in a dose-dependent manner, with EC50 values of 10.5, 6.6, 15.7, and 1.6M, whereas compounds 1, 8, and 9 demonstrated transactivational PPAR() effects with EC50 values of 11.4, 10.3, and 1.5M, respectively. These results provide a scientific rationale for the use of the roots of S. flavescens and warrant further studies to develop new agents for the prevention and treatment of inflammatory and metabolic diseases. Copyright (c) 2012 John Wiley & Sons, Ltd.