Ginkgo terpene component has an anti-inflammatory effect on Candida albicans-caused arthritic inflammation

The Ginkgo biloba extract, EGb 761, contains flavonoid glycosides and unique terpene lactones as major active components. In this study, we determined the anti-inflammatory effect of the water-soluble portion (GH415) of the EGb 761 on the inflammation caused by Candida albicans, a major ethiological agent that causes fungal arthritis. For inflammatory induction, an emulsified mixture of C. albicans cell wall and Complete Freund's Adjuvant (CACW/CFA) was injected into BALB/c mice by the hind footpad route once a day for 3 days. Twenty-four hours after the final injection, mice having the swollen footpad were given the GH415 (2 mg/dose) intraperitoneally to the mice once every 3 days for 15 days. The footpad-swelling of these mice was measured during the entire observation period. Results showed that the GH415 treatment reduced the swelling. In the same animal model, this effect was enhanced by treatment with the GH415 entrapped within liposome (Lipo-GH: 200 μ/dose). Further analysis revealed that terpene, not flavone portion, was responsible for such therapeutic anti-inflammatory effect. Treatment with the terpene (7.4 μg/dose) by liposomal delivery method had similar effects as the treatment with indomethacin at 30 μg/dose. Addition of the terpene to lipopolysaccharide-treated macrophages showed suppression of nitric oxide (NO) production. These results suggest that blockage of the NO production from the macrophages that infiltrated to the inflamed site may be a possible mechanism for the therapeutic anti-inflammatory effect.