Anti-inflammatory and PPAR Transactivational Effects of Components from the Stem Bark of Ginkgo biloba

Abstract

Ginkgo biloba, which is considered a "living fossil", has been used for medicinal purposes for thousands of years. Currently, extracts of G. biloba are some of the most widely used herbal products and/or dietary supplements in the world. In this study, three new compounds, (2E,4E,1'R,3'S,5'R,8'S)-dihydrophaseic acid 3'-O-beta-D-glucopyranoside (1), 7,8-dihydro-(R)-7-methoxyconiferyl alcohol (2), and (8S)-3-methoxy-8,4'-oxyneolignan-4,9,9'-triol 3'-O-beta-D-glucopyranoside (3), and 13 known compounds (4-16) were isolated from the stem bark of G. biloba. Their structures were determined by extensive spectroscopic methods, including ID and 2D NMR, MS, and circular dichroism spectra. Four of the compounds (1, 2, 7, and 10) inhibited TNF alpha-induced NF-kappa B transcriptional activity significantly in HepG2 cells in a dose-dependent manner, with IC50 values ranging from 6.9 to 9.1 mu M. Furthermore, the transcriptional inhibitory function of these compounds was confirmed based on decreases in COX-2 and iNOS gene expression in HepG2 cells. Compounds 1-5, 7, 9, 10, and 12-14 significantly activated the transcriptional activity of PPARs in a dose-dependent manner, with EC50 values ranging from 0.7 to 12.8 mu M. Compounds 2, 3, and 12 exhibited dose-dependent PPAR alpha transactivational activity, with EC50 values of 7.0, 3.3, and 10.1 mu M, respectively. Compounds 1-3 activated PPAR gamma transcriptional activity, with EC50 values of 11.9, 11.0, and 15.3 mu M, whereas compounds 1 and 3 promoted the transactivational activity of PPAR beta(delta) with EC50 values of 10.7 and 11.2 mu M, respectively. These results provide a scientific support for the use of G. biloba stem bark for the prevention and treatment of inflammatory and metabolic diseases. Moreover, these data provide the rationale for further studies of the potential of G. biloba stem bark in functional foods.