Although the etiology of chronic skin inflammatory disorders including psoriasis and atopic dermatitis (AD) is not clearly understood, many studies have shown that various proinflammatory enzymes/cytokines play an important role in these inflammatory diseases. For example, phospholipase A 2 (PLA 2 ) was highly expressed in some psoriatic tissues. 1) In addition to lipoxygenase products, 2) cyclooxygenase (COX) and prostaglandins (PG) were involved in dermal inflammation and skin wound healing.

more »

... ,4) Moreover, it was found that high concentrations of cytokines, such as tumor necrosis factor (TNF)-a, and adhesion molecules, including intercellular adhesion molecule (ICAM)-1, were deeply involved in the regional site of chronic skin inflammation. 5,6) Recent studies have also indicated that inducible nitric oxide synthase (iNOS) may be associated with psoriasis, and its reaction product, NO, is involved in various skin disorders. 7,8) Therefore, it is reasonably thought that an interference of activity and/or expression of these proinflammatory molecules may result in attenuation of chronic skin inflammatory syndromes, and the agents acting on these points may give beneficial effects. Biflavonoids are flavonoid-flavonoid dimers and some of them possess anti-inflammatory activity. For instance, several biflavonoids including amentoflavone, ginkgetin and isoginkgetin inhibited histamine release. 9) Amentoflavone and tetrahydroamentoflavone were found to inhibit COX-1 and/or COX-2. 10,11) Some biflavonoids were revealed to suppress the expression of proinflammatory molecules such as COX-2 and iNOS. 12,13) These previous investigations have shown the potential of certain biflavonoids for anti-inflammatory agents. In particular, ginkgetin (Fig. 1 ) mainly found in Ginkgo biloba leaves (Ginkgoaceae) was previously demonstrated as an inhibitor of group IIA sPLA 2 inhibitor 14) and cPLA 2 . 15) In addition, ginkgetin was reported to suppress COX-2 expression from lipopolysaccharide (LPS)-treated macrophages without affecting COX-2 activity, and in vivo study has also revealed that ginkgetin inhibited COX-2 expression and PGE 2 production from mouse skin induced by 3-d treatment of 12-O-tetradecanoylphorbol-13-acetate Ginkgetin, a biflavonoid from Ginkgo biloba leaves (Ginkgoaceae), was previously demonstrated to inhibit phospholipase A 2 and to suppress proinflammatory gene expression such as cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase. In this study, the effects of ginkgetin were examined on an animal model of chronic skin inflammation and proinflammatory gene expression. When topically applied to ICR mouse ear, ginkgetin (20-80 m mg/ear/treatment) inhibited ear edema (22.8-30.5%) and prostaglandin E 2 production (30.2-31.1%) induced by multiple treatment of 12-O-tetradecanoylphorbol-13-acetate (TPA) for 7 consecutive days. By histological comparison, ginkgetin was also found to reduce epidermal hyperplasia. The expression of proinflammatory gene, interleukin-1b b, was suppressed by ginkgetin. From the results, it is suggested that ginkgetin may be beneficial against chronic skin inflammatory disorders like atopic dermatitis.