Department of Biotechnology, Institute of Animal Molecular Biotechnology, Korea University, Seoul, Republic of Korea.
Department of Animal Science, Center for Animal Biotechnology and Genomics, Texas A&M University, College Station, Texas.
J Cell Physiol. 2019 Apr;234(4):4327-4341. doi: 10.1002/jcp.27212. Epub 2018 Aug 25.
Silibinin is a flavonolignan extracted from milk thistle, which has been used for treating liver disorders, various cancers, and gynecological diseases. However, attempts for treating endometriosis with silibinin are lacking. In this study, we observed that silibinin exerts antiproliferative and apoptotic effects on human endometriotic cell lines VK2/E6E7 and End1/E6E7. We also identified that silibinin-induced oxidative stress and lipid peroxidation in human endometriotic cells. Moreover, we observed upregulation of calcium concentration in the cytosol and mitochondrial matrix, which resulted in mitochondrial dysfunction. Furthermore, induction of endoplasmic reticulum stress signals with rapid mitogen-activated protein kinase (MAPK) pathway signaling resulted in apoptosis of both cells. Using an animal model mimicking the retrograde menstruation hypothesis, we verified the effects of silibinin on reducing endometriotic lesions by inhibiting the expression of inflammatory cytokines in mice. Silibinin might be used as a novel therapeutic agent or supplement for inhibiting progression of endometriosis in vitro and in vivo.
水飞蓟宾是从奶蓟草中提取的一种黄酮木脂素，已被用于治疗肝脏疾病、各种癌症和妇科疾病。然而，用水飞蓟宾治疗子宫内膜异位症的尝试还很少。在这项研究中，我们观察到水飞蓟宾对人子宫内膜异位细胞系 VK2/E6E7 和 End1/E6E7 具有抗增殖和促凋亡作用。我们还发现水飞蓟宾诱导人子宫内膜异位细胞的氧化应激和脂质过氧化。此外，我们观察到细胞溶质和线粒体基质中钙浓度的上调，导致线粒体功能障碍。此外，内质网应激信号的诱导伴随着快速有丝分裂原激活蛋白激酶（MAPK）信号通路的信号转导，导致两种细胞的凋亡。通过模拟逆行性月经假说的动物模型，我们验证了水飞蓟宾通过抑制小鼠炎症细胞因子的表达来减少子宫内膜异位病变的作用。水飞蓟宾可能被用作一种新型治疗剂或补充剂，用于抑制体外和体内子宫内膜异位症的进展。
