Monden Tsuyoshi, Hosoya Takeshi, Nakajima Yasuyo, Kishi Mikiko, Satoh Teturou, Hashimoto Koshi, Kasai Kikuo, Yamada Masanobu, Mori Masatomo
Department of Endocrinology and Metabolism, Dokkyo University School of Medicine, Mibu, Tochigi, Japan.
Endocr J. 2008 Jul;55(3):529-33. doi: 10.1507/endocrj.k07e-101. Epub 2008 May 9.
Hachimi-jio-gan is widely used to improve several disorders associated with diabetes, but its mechanism remains poorly understood. In an attempt to clarify the mechanism of Hachimi-jio-gan, we investigated the effects of this herbal medicine and its components in transfection studies of CV1 cells, especially nuclear receptor-mediated actions. One half (0.5) mg/ml of Hachimi-jio-gan activated peroxisome proliferator-activated receptor (PPARalpha), mediating the activation by 3.1-fold on DR1 response elements; however, it did not affect PPARgamma, thyroid hormone receptor, androgen receptor, estrogen receptor or RXR. In addition, this activation was observed in a dose-dependent manner. Next, to determine which components of Hachimi-jio-gan activate PPARalpha-mediated transcription, 8 of its components (rehmanniae radix, orni fructus, dioscoreae rhizoma, alismatis rhizoma, hoelen, moutan cortex, cinnamomi cortex, aconiti) were tested. Only cinnamomi cortex (1.0 mg/ml) increased PPARalpha-mediated transcription by 4.1-fold, and this activation was specific for PPAR alpha, and not for other nuclear receptors. Moreover, this PPARalpha-related activation by cinnamomi cortex is specifically observed in renal cells. Taken together, these findings indicate that Hachimi-jio-gan and cinnamomi cortex may have a pharmacological effect through the target site for PPARalpha.
八味地黄丸被广泛用于改善多种与糖尿病相关的病症，但其作用机制仍知之甚少。为了阐明八味地黄丸的作用机制，我们在CV1细胞转染研究中调查了这种草药及其成分的作用，特别是核受体介导的作用。0.5毫克/毫升的八味地黄丸激活了过氧化物酶体增殖物激活受体（PPARα），使DR1反应元件上的激活增加了3.1倍；然而，它对PPARγ、甲状腺激素受体、雄激素受体、雌激素受体或RXR没有影响。此外，这种激活呈剂量依赖性。接下来，为了确定八味地黄丸的哪些成分激活PPARα介导的转录，测试了其8种成分（熟地黄、山茱萸、山药、泽泻、茯苓、牡丹皮、肉桂、附子）。只有肉桂（1.0毫克/毫升）使PPARα介导的转录增加了4.1倍，并且这种激活对PPARα具有特异性，对其他核受体则没有。此外，肉桂引起的这种与PPARα相关的激活在肾细胞中特异性地观察到。综上所述，这些发现表明八味地黄丸和肉桂可能通过PPARα的靶点产生药理作用。
