Koseki Junichi, Matsumoto Takashi, Matsubara Yosuke, Tsuchiya Kazuaki, Mizuhara Yasuharu, Sekiguchi Kyoji, Nishimura Hiroaki, Watanabe Junko, Kaneko Atsushi, Hattori Tomohisa, Maemura Kazuya, Kase Yoshio
Tsumura Research Laboratories, Tsumura & Co., 3586 Yoshiwara, Ami-machi, Inashiki-gun, Ibaraki 300-1192, Japan.
Kampo Formulations Development Center, Tsumura & Co., 3586 Yoshiwara, Ami-machi, Inashiki-gun, Ibaraki 300-1192, Japan.
Evid Based Complement Alternat Med. 2015;2015:853846. doi: 10.1155/2015/853846. Epub 2015 Jan 29.
Objective. Bokusoku (BK) is an extract from the Quercus cortex used in folk medicine for treatment of skin disorders and convergence, and is present in jumihaidokuto, a traditional Japanese medicine that is prescribed for purulent skin diseases like acne vulgaris. The excess of sebum production induced by androgen is involved in the development of acne. Our aim is to examine whether BK and its constituents inhibit testosterone metabolism and testosterone-induced sebum synthesis. Methods. Measurements of 5α-reductase activity and lipogenesis were performed using rat liver microsomes and hamster sebocytes, respectively. Results. BK dose-dependently reduced the conversion of testosterone to a more active androgen, dihydrotestosterone in a 5α-reductase enzymatic reaction. Twenty polyphenols in BK categorized as gallotannin, ellagitannin, and flavonoid were identified by LC-MS/MS. Nine polyphenols with gallate group, tetragalloyl glucose, pentagalloyl glucose, eugeniin, 1-desgalloyl eugeniin, casuarinin, castalagin, stenophyllanin C, (-)-epicatechin gallate, and (-)-epigallocatechin gallate, inhibited testosterone metabolism. In particular, pentagalloyl glucose showed the strongest activity. BK and pentagalloyl glucose suppressed testosterone-induced lipogenesis, whereas they weakly inhibited the lipogenic action of insulin. Conclusions. BK inhibited androgen-related pathogenesis of acne, testosterone conversion, and sebum synthesis, partially through 5α-reductase inhibition, and has potential to be a useful agent in the therapeutic strategy of acne.
目的。朴树皮(BK)是从槲树皮中提取的成分,在民间医学中用于治疗皮肤疾病和收敛,并且存在于十味败毒汤中,这是一种用于治疗寻常痤疮等化脓性皮肤病的传统日本药物。雄激素诱导的皮脂分泌过多与痤疮的发生有关。我们的目的是研究BK及其成分是否抑制睾酮代谢和睾酮诱导的皮脂合成。方法。分别使用大鼠肝微粒体和仓鼠皮脂腺细胞进行5α-还原酶活性和脂肪生成的测定。结果。在5α-还原酶酶促反应中,BK剂量依赖性地减少了睾酮向活性更高的雄激素双氢睾酮的转化。通过液相色谱-串联质谱法(LC-MS/MS)鉴定出BK中的20种多酚,分为没食子单宁、鞣花单宁和类黄酮。9种带有没食子酸基团的多酚,四没食子酰葡萄糖、五没食子酰葡萄糖、诃子鞣质、1-去没食子酰诃子鞣质、木麻黄鞣质、栗木鞣质、窄叶紫金牛素C、(-)-表儿茶素没食子酸酯和(-)-表没食子儿茶素没食子酸酯,抑制睾酮代谢。特别是,五没食子酰葡萄糖表现出最强的活性。BK和五没食子酰葡萄糖抑制睾酮诱导的脂肪生成,而它们对胰岛素的脂肪生成作用抑制较弱。结论。BK抑制痤疮的雄激素相关发病机制、睾酮转化和皮脂合成,部分是通过抑制5α-还原酶,并且有潜力成为痤疮治疗策略中的一种有用药物。