Enomoto Riyo, Suzuki Chie, Koshiba Chika, Nishino Takayuki, Nakayama Mikiko, Hirano Hiroyuki, Yokoi Toshio, Lee Eibai
Department of Pharmacology, Faculty of Pharmaceutical Sciences, Kobe Gakuin University, Ikawadani-cho, Nishi-ku, Kobe 651-2180, Japan.
Ann N Y Acad Sci. 2007 Jan;1095:412-7. doi: 10.1196/annals.1397.044.
Glucocorticoid, such as dexamethasone, has anti-inflammatory and immunosuppressive action as major pharmacological effects. The latter action caused by lymphocyte apoptosis is not only a therapeutic effect but also an adverse reaction. Wogonin, a plant flavone found in Scutellaria baicalensis Georgi, inhibited dexamethasone-induced apoptotic changes, such as DNA fragmentation, nuclear condensation, phosphatidylserine translocation, and caspase activation in rat thymocytes. Since wogonin inhibited dexamethasone-induced DNA fragmentation in a noncompetitive manner, a target of this flavone is unlikely to be an antagonist of glucocorticoid receptor. Wogonin did not only act as an inhibitor of caspases, but also protected apoptosis induced by other glucocorticoids. Since wogonin reduced one of the major pharmacological effects of dexamethasone, we examined whether this flavone diminishes the anti-inflammatory action, another pharmacological effect. The anti-inflammatory action of dexamethasone was evaluated by carrageenan-induced paw edema model. Although dexamethasone significantly suppressed paw edema induced by carrageenan, wogonin had no effect on the anti-inflammatory action of dexamethasone. These results suggest that wogonin may be a useful compound to reduce the immunosuppressive side effect of glucocorticoid.
糖皮质激素，如地塞米松，具有抗炎和免疫抑制作用，这是其主要药理作用。由淋巴细胞凋亡引起的后者作用不仅是一种治疗效果，也是一种不良反应。汉黄芩素是从黄芩中发现的一种植物黄酮，它抑制了地塞米松诱导的大鼠胸腺细胞凋亡变化，如DNA片段化、核浓缩、磷脂酰丝氨酸易位和半胱天冬酶激活。由于汉黄芩素以非竞争性方式抑制地塞米松诱导的DNA片段化，这种黄酮的靶点不太可能是糖皮质激素受体的拮抗剂。汉黄芩素不仅作为半胱天冬酶的抑制剂起作用，还能保护由其他糖皮质激素诱导的凋亡。由于汉黄芩素降低了地塞米松的一种主要药理作用，我们研究了这种黄酮是否会减弱另一种药理作用——抗炎作用。地塞米松的抗炎作用通过角叉菜胶诱导的爪肿胀模型进行评估。虽然地塞米松显著抑制了角叉菜胶诱导的爪肿胀，但汉黄芩素对地塞米松的抗炎作用没有影响。这些结果表明，汉黄芩素可能是一种有用的化合物，可减少糖皮质激素的免疫抑制副作用。
