Tsumura Kampo Research Laboratories, Kampo Research and Development Division, Tsumura & Co., 3586 Yoshiwara, Ami-machi, Inashiki-gun, Ibaraki, 300-1192, Japan.
J Nat Med. 2021 Mar;75(2):361-371. doi: 10.1007/s11418-020-01474-x. Epub 2021 Jan 4.
Shimotsuto is a traditional Japanese Kampo medicine used to treat gynecological diseases, such as irregular menstruation, in addition to oversensitivity to cold and chilblains. Part of the pharmacological actions of shimotsuto is traditionally considered to be exerted by an improvement effect of the blood and the circulatory system. Multiple ingredients (e.g., catalpol and paeoniflorin) contained in shimotsuto have been reported to have pharmacological activities on the blood and circulatory system, and thus been considered to contribute to the pharmacological actions of shimotsuto. However, it remains unclear whether the ingredients can be absorbed into the body following oral administration of shimotsuto. The aim in the present study was to specify shimotsuto ingredient absorbed into the systemic circulation in rats. Seven candidate active ingredients (catalpol, paeoniflorin, albiflorin, ligustilide, senkyunolide A, butylphthalide, and ferulic acid) in plasma after oral administration of shimotsuto were quantified by targeted liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis. This study also performed nontargeted LC-MS/MS analysis of plasma following administration of constituent crude drugs of shimotsuto to find extensively blood-absorbed ingredients of shimotsuto. Among detected peaks in the nontargeted analysis, two peaks could be identified as bergapten and 8-debenzoylpaeoniflorin, subsequently their concentrations in shimotsuto-treated rat plasma were quantified. These pharmacokinetic studies indicated that catalpol showed the highest plasma concentration following administration of shimotsuto, followed by 8-debenzoylpaeoniflorin. This study suggests that all nine ingredients are absorbed into the blood following oral administration of shimotsuto and possibly contribute to its pharmacological action.
下口津是一种传统的日本汉方药，用于治疗妇科疾病，如月经不调，以及对寒冷和冻疮的过度敏感。下口津的部分药理作用传统上被认为是通过改善血液和循环系统的作用发挥的。下口津中含有的多种成分（如梓醇和芍药苷）已被报道具有对血液和循环系统的药理活性，因此被认为对上口津的药理作用有贡献。然而，口服下口津后，这些成分是否能被吸收到体内仍不清楚。本研究的目的是确定下口津中被吸收到全身循环系统的成分。通过靶向液相色谱-串联质谱（LC-MS/MS）分析，在下口津口服后血浆中定量了 7 种候选活性成分（梓醇、芍药苷、白芍苷、藁本内酯、川芎嗪 A、丁基苯酞和阿魏酸）。本研究还在下口津组成药材给药后对血浆进行了非靶向 LC-MS/MS 分析，以寻找广泛吸收的下口津成分。在非靶向分析中检测到的峰中，有两个峰可以鉴定为佛手柑内酯和 8-去苯甲酰基芍药苷，随后定量了它们在下口津处理的大鼠血浆中的浓度。这些药代动力学研究表明，梓醇在下口津给药后表现出最高的血浆浓度，其次是 8-去苯甲酰基芍药苷。本研究表明，口服下口津后，所有 9 种成分都被吸收到血液中，可能对其药理作用有贡献。
