Cho Min Kyoung, Jin Ling, Han Jung Ho, Jin Jung-Suk, Cheon Se-Yun, Shin Su, Bae Sung-Jin, Park Jang-Kyung, Ha Ki-Tae
Korean Medical Research Center for Healthy Aging, Pusan National University, Yangsan, South Korea.
Department of Korean Medical Science, School of Korean Medicine, Pusan National University, Yangsan, South Korea.
Front Pharmacol. 2022 Apr 4;13:872810. doi: 10.3389/fphar.2022.872810. eCollection 2022.
Endometriosis is a chronic inflammatory disorder caused by abnormal adhesion of endometrial tissue to the outside of the uterus. The combination of surgery, non-steroidal anti-inflammatory drugs, and hormone treatment is well established therapy for endometriosis, however, case reports have showed that high rates of relapse and unpleasant side effect. For these reasons, recently, the studies have been focused on the Warburg-like metabolic shift of endometriosis. is one of traditionally used herbal medicine for inflammatory disease and the anti-estrogenic effects of is well-established. Therefore, in this work, we evaluated water-extracted (PV) as a potential treatment for endometriosis. To this, we artificially induced endometriosis in ovarectomized mice by intra-peritoneal inoculation of uterus extracts. PV was orally administered, and PV significantly alleviated endometriosis, particularly the growth of ectopic endometrial lesions in artificially endometriosis-induced mice. For the mechanism study of anti-endometriosis by PV, we designed an study using human normal endometrial stromal cells (T-HESCs) and human endometrial cell (12Z) obtained from patients with endometriosis. PV strongly induced the apoptosis of 12Z cells rather than T-HESCs by control the activity or expression of aerobic glycolysis enzymes, such as lactate dehydrogenase A (LDHA), pyruvate dehydrogenase A, and pyruvate dehydrogenase kinase 1/3. In addition, lactate production was enhanced, and oxygen consumption rate was suppressed in 12Z cells upon PV treatment. These changes in aerobic glycolysis eventually caused mitochondrial damage following decreased mitochondrial membrane potential and excessive mitochondrial ROS production. Especially, ulsolic acid (UA), one of the compounds in PV considerably led 12Z cell apoptosis with inhibition of LDHA activity. Therefore, UA could be a major active substance of PV in terms of endometriosis inhibitors. In conclusion, this study provides the evidence that the beneficial efficacy of PV for the prevention/treatment of endometriosis.
子宫内膜异位症是一种慢性炎症性疾病，由子宫内膜组织异常附着于子宫外部引起。手术、非甾体抗炎药和激素治疗的联合应用是子宫内膜异位症的既定疗法，然而，病例报告显示复发率高且副作用令人不适。由于这些原因，最近的研究集中在子宫内膜异位症的沃伯格样代谢转变上。[某种草药名称]是传统上用于治疗炎症性疾病的草药之一，其抗雌激素作用已得到充分证实。因此，在这项研究中，我们评估了水提取的[该草药名称]（PV）作为子宫内膜异位症的潜在治疗方法。为此，我们通过腹腔接种子宫提取物在去卵巢小鼠中人工诱导子宫内膜异位症。口服给予PV，PV显著减轻了子宫内膜异位症，特别是在人工诱导子宫内膜异位症的小鼠中异位子宫内膜病变的生长。为了研究PV抗子宫内膜异位症的机制，我们设计了一项使用从子宫内膜异位症患者获得的人正常子宫内膜基质细胞（T-HESCs）和人子宫内膜细胞（12Z）的研究。PV通过控制有氧糖酵解酶（如乳酸脱氢酶A（LDHA）、丙酮酸脱氢酶A和丙酮酸脱氢酶激酶1/3）的活性或表达，强烈诱导12Z细胞凋亡，而不是T-HESCs。此外，PV处理后12Z细胞中的乳酸产生增加，氧消耗率受到抑制。有氧糖酵解的这些变化最终导致线粒体膜电位降低和线粒体ROS产生过多后线粒体损伤。特别是，熊果酸（UA）是PV中的一种化合物，通过抑制LDHA活性显著导致12Z细胞凋亡。因此，就子宫内膜异位症抑制剂而言，UA可能是PV的主要活性物质。总之，本研究提供了证据表明PV对预防/治疗子宫内膜异位症具有有益疗效。
