Potency of Tokishakuyakusan in treating preeclampsia: Drug repositioning method by in vitro screening of the Kampo library.
Potency of Tokishakuyakusan in treating preeclampsia: Drug repositioning method by in vitro screening of the Kampo library.
复制标题
DOI：
10.1371/journal.pone.0244684
复制
发表时间：
2020
期刊：
影响因子：
3.7
通讯作者：
Kimura T
中科院分区：
文献类型：
--
作者：
Yagi K;Mimura K;Tomimatsu T;Matsuyama T;Kawanishi Y;Kakigano A;Nakamura H;Endo M;Kimura T
除终止妊娠外，子痫前期治疗尚未建立。本研究的目的是利用药物定位法从日本传统中药（汉方药）中寻找一种潜在的治疗药物。我们筛选了74个柬埔寨人的文库，以确定治疗先兆子痫的潜在药物。我们利用人脐静脉内皮细胞（HUVECs）研究了这些药物的血管生成作用。采用酶联免疫吸附法测定各药物100 μg/mL的条件培养基中胎盘生长因子（PlGF）的水平。我们评估筛选的药物是否影响细胞活力。我们进行了血管形成实验来评估诱导plgf的药物的血管生成作用。在剂量相关性实验中给药10、50、100、200 μg/mL后，在时间过程实验中分别于1、2、3、6、12、24 h测定PlGF。我们还用候选药物和100 ng/mL可溶性纤维样酪氨酸激酶1 （sFlt1）进行了试管形成实验。候选药物在滋养细胞（BeWo和HTR-8/SVneo）中产生PlGF。进行Mann-Whitney U检验或单向方差分析，然后进行Newman-Keuls事后检验。p值< 0.05为显著性。在7种诱导PlGF的药物中，Tokishakuyakusan （TS）、Shoseiryuto和Shofusan没有降低细胞活力。TS显著促进导管形成（P = 0.017）。TS给药增加PlGF表达呈剂量和时间依赖性。TS显著改善了小管的形成，sFlt1抑制了小管的形成（P = 0.033）。TS也增加了BeWo细胞的PlGF产量（P = 0.001），但没有增加HTR-8/SVneo细胞的PlGF产量（P = 0.33）。通过药物重定位法对Kampo文库进行体外筛选，我们发现TS可能具有治疗先兆子痫的潜力。其新发现的机制包括增加PlGF的产生和改善抗血管生成状态。
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. 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. 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). 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.
登录
查看更多内容
影响因子：
3.8
作者：
Romani, F.;Lanzone, A.;Apa, R.
通讯作者：
Apa, R.
影响因子：
5.8
作者：
Miller, Susanne C.;Huang, Ruili;Sakamuru, Srilatha;Shukla, Sunita J.;Attene-Ramos, Matias S.;Shinn, Paul;Van Leer, Danielle;Leister, William;Austin, Christopher P.;Xia, Menghang
通讯作者：
Xia, Menghang
影响因子：
15.8
作者：
Fisk NM;Atun R
通讯作者：
Atun R
影响因子：
15.9
作者：
Ernst, E
通讯作者：
Ernst, E
DOI：
10.1073/pnas.1011293108
发表时间：
2011-01-25
影响因子：
11.1
作者：
Kumasawa, Keiichi;Ikawa, Masahito;Okabe, Masaru
通讯作者：
Okabe, Masaru