The aerial parts of Artemisia capillaris Thunberg (Compositae) have been used in Chinese medicine as a liver protective agent, diuretic, and for amelioration of skin inflammatory conditions. This study was conducted to establish the scientific rationale for treating skin inflammation and to find active principles from A. capillaris. To accomplish these goals, the 70% ethanol extract of the aerial parts of A. capillaris (AR) was prepared and its 5-lipoxygenase (5-LOX) inhibitory action was studied since 5-LOX products are known to be involved in several allergic and skin inflammatory disorders. AR showed potent inhibitory activity against 5-LOX-catalyzed leukotriene production by ionophore-induced rat basophilic leukemia-1 cells, with an IC(50) of < 1.0 μg/mL. Nine major compounds, scopoletin, scopolin, scoparone, esculetin, quercetin, capillarisin, isorhamnetin, 3-O-robinobioside, isorhamnetin 3-O-galactoside and chlorogenic acid, were isolated from A. capillaris, and their effects were examined to identify the active principle(s). Several coumarin and flavonoid derivatives were found to be 5-LOX inhibitors. In particular, esculetin and quercetin were potent inhibitors, with IC(50) values of 6.6 and 0.7 μM, respectively. Against arachidonic acid-induced ear edema in mice, AR, and esculetin strongly inhibited edematic response. AR and esculetin also inhibited delayed-type hypersensitivity response in mice. In conclusion, AR and some of their major constituents are 5-LOX inhibitors, and these in vitro and in vivo activities may contribute to the therapeutic potential of AR in skin inflammatory disorders in traditional medicine.

The 70% ethanol extract of the rhizome of Alisma orientale (Alismatis rhizome) (AOE) was prepared and found to significantly inhibit 5-lipoxygenase (5-LOX)-catalyzed leukotriene (LT) production from rat basophilic leukemia (RBL)-1 cells and β-hexosaminidase release by antigen-stimulated RBL-2H3 cells. It also attenuated delayed-type hypersensitivity (DTH) reaction in mice. Among the three major triterpene constituents isolated (i.e., alisol B, alisol B 23-acetate, alisol C 23-acetate) as active principles, alisol B and its 23-acetate strongly and significantly inhibited LT production and β-hexosaminidase release between 1-10 µM. On the other hand, all these alisol derivatives significantly and strongly inhibited DTH response after oral administration. In addition, AOE (200 mg/kg/d) was for the first time found to considerably alleviate hapteninduced dermatitis symptoms in NC/Nga mice, an animal model of atopic dermatitis. These results indicate that alisol derivatives possess inhibitory activities on immediate-type as well as delayed-type hypersensitivity reactions and may contribute to the anti-allergic action of AOE.Key words Alisma orientale; alisol B; 5-lipoxygenase; β-hexosaminidase; anti-allergy; atopic dermatitisThe rhizome of Alisma orientale (Alismatis rhizome, Alismataceae) is a well-known Chinese traditional medicine. This plant material has been widely used as an anti-inflammatory drug in Asia 1) and the major constituents are alisol derivatives.2) Previously, the extract of A. orientale was reported to show anti-inflammatory and anti-allergic activities. Specifically, the methanol extract of A. orientale inhibited nitric oxide (NO) production.3) The methanol extract also showed anti-complement and anti-inflammatory activities while several alisol derivatives (alisol A, alisol A acetate, alisol B and alisol B acetate) exhibited anti-complement activity. 4,5) The same plant material inhibited contact dermatitis and cotton pellet granuloma at a high dose of 20 g/kg.6) In addition, the methanol extract showed anti-allergic actions against types I-IV hypersensitivity. 7) Several triterpenes and sesquiterpenes including alisol A, alisol B and alismol were found to be active against type III hypersensitivity reaction in rats with alisol B acetate being the most potent. Among the isolated compounds, alismol and several alisol derivatives such as alisol A and alisol B also inhibited NO production. 3,8) Recently, 13β,17β-epoxy alisol A and alisol B acetate were found to have immunosuppressive properties on lymphocytes.9) All these previous investigations have shown that A. orientale possesses anti-allergic activity and several constituents had inhibitory activity against type III hypersensitivity. However, these studies are far from complete. Anti-allergic activity of major constituents including alisol B, alisol B 23-acetate and alisol C 23-acetate against other types of hypersensitivity reaction have not been demonstrated and the effect of A. orientale on atopic dermatitis (AD) has not been investigated.Thu...