論文 - 詳細
| RRC ID | 63244 |
|---|---|
| 著者 | Yagi K, Mimura K, Tomimatsu T, Matsuyama T, Kawanishi Y, Kakigano A, Nakamura H, Endo M, Kimura T. |
| タイトル | Potency of Tokishakuyakusan in treating preeclampsia: Drug repositioning method by in vitro screening of the Kampo library. |
| ジャーナル | PLoS One |
| 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. |
| 巻・号 | 15(12) |
| ページ | e0244684 |
| 公開日 | 2020-1-1 |
| DOI | 10.1371/journal.pone.0244684 |
| PII | PONE-D-20-21074 |
| PMID | 33378412 |
| PMC | PMC7773249 |
| MeSH | Adult Cell Survival / drug effects Drug Repositioning* Drugs, Chinese Herbal / pharmacology* Drugs, Chinese Herbal / therapeutic use Female Human Umbilical Vein Endothelial Cells / drug effects* Human Umbilical Vein Endothelial Cells / metabolism Humans Medicine, Kampo* Placenta Growth Factor / metabolism* Pre-Eclampsia / drug therapy* Pregnancy Trophoblasts / drug effects Trophoblasts / metabolism |
| IF | 2.74 |
| リソース情報 | |
| ヒト・動物細胞 | BeWo |