Potency of Tokishakuyakusan in treating preeclampsia: Drug repositioning method by in vitro screening of the Kampo library

Abstract

Introduction Preeclampsia therapy has not been established, except for the termination of pregnancy. The aim of this study was to identify a potential therapeutic agent from traditional Japanese medicine (Kampo) using the drug repositioning method. Materials and methods We screened a library of 74 Kampo to identify potential drugs for the treatment of preeclampsia. We investigated the angiogenic effects of these drugs using human umbilical vein endothelial cells (HUVECs). Enzyme-linked immunosorbent assays were performed to measure the levels of placental growth factor (PlGF) in conditioned media treated with 100 μg/mL of each drug. We assessed whether the screened drugs affected cell viability. We performed tube formation assays to evaluate the angiogenic effects of PlGF-inducing drugs. PlGF was measured after administering 10, 50, 100, and 200 μg/mL of the candidate drug in the dose correlation experiment, and at 1, 2, 3, 6, 12, and 24 h in the time course experiment. We also performed tube formation assays with the candidate drug and 100 ng/mL of soluble fms-like tyrosine kinase 1 (sFlt1). PlGF production by the candidate drug was measured in trophoblastic cells (BeWo and HTR-8/SVneo). The Mann-Whitney U test or one-way analyses of variance followed by the Newman-Keuls post-hoc test were performed. P–values < 0.05 were considered significant. Results Of the 7 drugs that induced PlGF, Tokishakuyakusan (TS), Shoseiryuto, and Shofusan did not reduce cell viability. TS significantly facilitated tube formation (P = 0.017). TS administration increased PlGF expression in a dose- and time-dependent manner. TS significantly improved tube formation, which was inhibited by sFlt1 (P = 0.033). TS also increased PlGF production in BeWo (P = 0.001) but not HTR-8/SVneo cells (P = 0.33). Conclusions By using the drug repositioning method in the in vitro screening of the Kampo library, we identified that TS may have a therapeutic potential for preeclampsia. Its newly found mechanisms involve the increase in PlGF production, and improvement of the antiangiogenic state.

A Chinese Medicine, Tokishakuyakusan, Increases Bovine Oviductal Tonus <i>via</i> G Protein-Coupled Estrogen Receptor 1

“…The doses of TSS, G-1, and G-15 were based on the concentrations in previous reports. [28][29][30] The isometric tension of each strip was continuously recorded using a force-displacement transducer (Minebea Co., Ltd., Nagano, Japan) connected to a polygraph (Yokogawa Electric Corp., Tokyo, Japan). Since there was no difference in the results between Stage II and Stage III, they were merged into the same group in experiments 1-3.…”

Clinical Effects of Integrated Traditional Chinese and Western Medicine in Treating Severe Preeclampsia and Its Influence on Maternal and Infant Outcomes after Cesarean Section under Combined Lumbar and Epidural Anesthesia

“…However, there are individual differences in the effect of magnesium sulfate, which may lead to magnesium poisoning and poor safety [8]. According to the traditional Chinese medicine system, preeclampsia belongs to the category of "pregnancy vertigo" and "gestational vertigo" [9]. During pregnancy, the accumulation of Yin and blood, deficiency of essential qi, imbalance of Yin and Yang of liver and kidney, and disorder of qi and blood result in eclampsia [9].…”

“…According to the traditional Chinese medicine system, preeclampsia belongs to the category of "pregnancy vertigo" and "gestational vertigo" [9]. During pregnancy, the accumulation of Yin and blood, deficiency of essential qi, imbalance of Yin and Yang of liver and kidney, and disorder of qi and blood result in eclampsia [9]. erefore, one hundred and sixty-six cases of SPE in our hospital were treated with TCM decoction with magnesium sulfate and other conventional treatment, and the outcomes were satisfactory.…”