Pharmacokinetic study of traditional Japanese Kampo medicine shimotsuto used to treat gynecological diseases in rats

Mikina Takiyama,Junko Watanabe,Takashi Matsumoto,Sho Sanechika

doi:10.1007/s11418-020-01474-x

Mikina Takiyama, Junko Watanabe + Show 2 more

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https://doi.org/10.1007/s11418-020-01474-x

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Abstract

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.Graphic abstract

Highlights

Some herbal medicines have been used to treat gynecological diseases, especially in Asia [1,2,3]
The ingredients may be the active ingredients in shimotsuto, it is unclear whether they are absorbed into the body after oral administration of shimotsuto
The rats were fasted for 16 h and orally administered shimotsuto extract powder suspended in distilled water at a dosage of 1 g/10 mL/kg

Summary

Introduction

Some herbal medicines have been used to treat gynecological diseases, especially in Asia [1,2,3]. The pharmacological actions of these medicines are believed to be due to their multiple ingredients, which act on multiple targets [4]. Journal of Natural Medicines (2021) 75:361–371 medicine) is a traditional Japanese Kampo medicine used to treat gynecological diseases. It comprises four crude drugs: Angelicae Acutilobae Radix, Paeoniae Radix, Rehmanniae Radix, and Cnidii Rhizoma (see Supplementary Table 1 for the original plant source and medicinal part of each crude drug). The ingredients may be the active ingredients in shimotsuto, it is unclear whether they are absorbed into the body after oral administration of shimotsuto. The pharmacokinetic information is essential for identifying which ingredients of shimotsuto are active

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