Preventive Effect of Ginkgo biloba Extract (GBB) on the Lipopolysaccharide-Induced Expressions of Inducible Nitric Oxide Synthase and Cyclooxygenase-2 via Suppression of Nuclear Factor-κB in RAW 264.7 Cells

During our ongoing efforts to identify bioactive natural products with anti-inflammatory activity, we produced an extract from Ginkgo biloba (GBB) which contains higher levels of the active principles terpene and biflavonoid than EGb, the standard commercially available extract. In the present study, we examined and compared the effects of these two extracts on lipopolysaccharide (LPS)-induced nitric oxide (NO) and prostaglandin E2 (PGE2) production by the RAW 264.7 macrophage cell line. Our data indicate that GBB is a more potent inhibitor of NO and PGE2 production than EGb 761, and it also significantly decreased tumor necrosis factor (TNF)-α release. Consistent with these observations, the protein and mRNA expression levels of inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2) were found to be inhibited by GBB in a dose-dependent manner. Furthermore, GBB inhibited the LPS-induced DNA binding activity of nuclear factor-κB (NF-κB), which was associated with the prevention of IκB degradation, and subsequently with decreased p65 protein level in the nucleus. These results suggest that GBB inhibits LPS-induced iNOS, COX-2 and TNF-α expressions through the down-regulation of NF-κB-DNA binding activity.