Faculty of Pharmacy, Keio University, 1-5-30 Shibakoen, Minato-ku, Tokyo, 105-8512, Japan.
Faculty of Pharmaceutical Sciences, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba, 278-8510, Japan.
J Nat Med. 2018 Jun;72(3):706-714. doi: 10.1007/s11418-018-1209-7. Epub 2018 Apr 18.
Orengedokuto is a Kampo formula that has been used for removing "heat" and "poison" to treat inflammation, hypertension, gastrointestinal disorders, and liver and cerebrovascular diseases. We report here our analysis of the anti-inflammatory effect of the component crude drugs of orengedokuto and their constituents using the inhibition of nitric oxide (NO) production in the murine macrophage-like cell line J774.1. An initial comparison of NO production inhibitory activities of the extracts of the component crude drugs and their combinations revealed that the activity could be attributed to Phellodendron Bark and Coptis Rhizome. Berberine (1), the major constituent of these crude drugs, showed potent activity (IC 4.73 ± 1.46 μM). Quantitative analysis of 1 in the extracts of all combinations of component crude drugs revealed that the amount of 1 in each extract of the combination of Scutellaria Root with either Phellodendron Bark and/or Coptis Rhizome was lower than that in the corresponding mixtures of the extracts of the individual crude drugs and that 1 was present in the precipitates formed during the decoction process. To the contrary, the differences in the amounts of 1 were smaller in the extracts containing Gardenia Fruit. These results indicated that the constituents of Scutellaria Root precipitated with 1 and that the constituents of Gardenia Fruit dissolved the precipitates. To identify the constituents affecting the solubility of 1, we fractionated the hot-water extracts of Scutellaria Root based on solubility tests of 1 to give baicalin (2), wogonin (3) and oroxyloside (4), which formed precipitates with 1.
葛根汤是一种汉方药，用于“祛热”“解毒”，治疗炎症、高血压、胃肠疾病、肝和脑血管疾病。我们在这里报告了我们使用鼠源巨噬细胞样细胞系 J774.1 分析葛根汤的组成药物及其成分的抗炎作用的结果，即抑制一氧化氮（NO）的产生。最初比较了组成药物及其组合提取物的 NO 产生抑制活性，结果表明该活性可归因于黄柏和黄连。这些原料药的主要成分小檗碱（1）表现出很强的活性（IC 4.73±1.46μM）。对所有组成药物组合提取物中 1 的定量分析表明，在黄柏和/或黄连与黄芩根组合的每个提取物中 1 的量低于相应的单个原料药提取物混合物中的量，并且 1 存在于煎煮过程中形成的沉淀物中。相反，栀子果提取物中 1 的含量差异较小。这些结果表明，黄芩根的成分与 1 一起沉淀，而栀子果的成分溶解了沉淀物。为了确定影响 1 溶解度的成分，我们根据 1 的溶解度试验对黄芩根的热水提取物进行了分级，得到了黄芩苷（2）、汉黄芩素（3）和连翘酯苷（4），它们与 1 形成沉淀物。
