The effects of Ginkgo biloba extract on lipopolysaccharide-induced inflammation in vitro and in vivo

Purpose. Ginkgo biloba extract (GBE) contains many different flavone glycosides and terpenoides. Several previous studies have demonstrated that GBE exhibits a wide variety of biological activities, including an antioxidant action, on which we focused our attention. The aim of the present study was to investigate the efficacy of GBE on endotoxin induced uveitis in rats. The anti-inflammatory potency of GBE in vivo was compared with that of prednisolone. In addition, we also investigated nitric oxide (NO), prostaglandin E2 (PGE2), tumor necrosis factor-alpha (TNF-alpha) and the expression of iNOS in a mouse macrophage cell line (RAW 264-7) treated with GBE in vitro to clarify the anti-inflammatory effect. Methods. EIU was induced in male Lewis rats by a footpad injection of lipopolysaccharide (LPS). Immediately after the LPS inoculation, either 1, 10 or 100 mug of GBE were injected intravenously. 24 hr later, the aqueous humor was collected from both eyes, and the number of infiltrating cells, protein concentration and NO level in the aqueous humor was determined. The RAW 264.7 cells were pretreated with various concentrations of GBE for 24 hr and subsequently incubated with LPS for 24 hr. Levels of NO, PGE2 and TNF-alpha were determined by enzyme-linked immunosorbent assay. The expression of iNOS protein was analyzed by Western blotting method. Results. GBE treatment in vivo decreased the concentrations of protein and NO in the aqueous humor of EIU rats. The anti-inflammatory effect of I mg GBE was as strong as that of same dose prednisolone. It also significantly reduced the concentration of PGE2, TNF-alpha and NO production in the medium of RAW 264.7 cells compared to that of the LPS group in vitro. The expression of iNOS protein in the 1000 mug ml(-1) of GBE treated cells decreased significantly. Conclusion. The present results indicate GBE suppresses the inflammation of EIU by blocking the iNOS protein expression and its antiinflammatory effect on eye is comparable with the effect of prednisolone used in similar doses. (C) 2004 Elsevier Ltd. All rights reserved.