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Front. Pharmacol. | doi: 10.3389/fphar.2019.01105

Gyejibongnyeong-hwan (Gui Zhi Fu Ling Wan) ameliorates human uterine myomas via apoptosis

 So Min Lee1, So Jin Shin2, Eunyoung Ha2, Chi Heum Cho2* and  Jeeyoun Jung1*
  • 1Korea Institute of Oriental Medicine (KIOM), South Korea
  • 2Keimyung University, South Korea

Uterine leiomyomas are the most common benign neoplasms in women of reproductive age. However, non-surgical treatments for uterine myomas have not been fully evaluated. In Korea and China, Gyejibongnyeong-hwan (GBH) is widely used to treat gynecological diseases. Thus, we investigated the effects of GBH in human uterine myoma cells (hUtMCs). The hUtMCs were collected from patients undergoing curative surgery. Cell viability was analyzed via 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays. The expression levels of p53, Bax, Bcl-2, cleaved-caspase-3, and caspase-9 were determined by western blotting. Apoptosis and ROS levels were evaluated by fluorescence microscopy. First, we determined the adequate concentration that did not affect normal cells, and then investigated the time-dependent anti-neoplastic effect of GBH in order to decide the appropriate treatment time under a non-toxic concentration. Cell viability and number were significantly reduced by GBH at 48 h (P < 0.001) in a dose-dependent manner (0–200 µg/mL). The ratio of Bax to Bcl2, and expression of p53, cleaved-caspase-3 and caspase-9 increased, representing GBH induced apoptosis in uterine leiomyomas. In addition, treatment of pan-caspase inhibitor/p53 inhibitor with GBH rescued the GBH-mediated apoptotic effect. Furthermore, GBH significantly increased the mitochondrial ROS concentration, and mitochondria ROS scavenger reduced the percentages of early apoptosis cell. These results suggest that GBH may induced apoptosis of leiomyomas and demonstrated that GBH can be a potential therapeutic and/or preventive agent for uterine leiomyomas.

Keywords: Uterine leiomyoma cell, Gyejibongnyeong-hwan, Apoptosis, Bax, Bcl-2

Received: 01 Feb 2019; Accepted: 28 Aug 2019.

Copyright: © 2019 Lee, Shin, Ha, Cho and Jung. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence:
MD. Chi Heum Cho, Keimyung University, Daegu, 704-701, North Gyeongsang, South Korea, c0035@dsmc.or.kr
MD. Jeeyoun Jung, Korea Institute of Oriental Medicine (KIOM), Daejeon, South Korea, jjy0918@kiom.re.kr