School of Medicine, Anhembi Morumbi University, Avenida Deputado Benedito Matarazzo 6070, Sao Jose dos Campos 12231-280, SP, Brazil.
Postgraduate Program in Biomedical Engineering, Department of Science and Technology, Federal University of Sao Paulo (UNIFESP), Rua Talim, 330, Vila Nair, Sao Jose dos Campos 12231-280, SP, Brazil.
Molecules. 2022 Jan 25;27(3):782. doi: 10.3390/molecules27030782.
Endometriosis presents high prevalence and its physiopathology involves hyperactivation of endometrial and vaginal cells, especially by bacteria. The disease has no cure and therapies aiming to inhibit its development are highly desirable. Therefore, this study investigated whether Miodesin (10 µg/mL = IC; 200 µg/mL = IC), a natural compound constituted by , , and astaxanthin, could exert anti-inflammatory and anti-proliferative effects against Lipopolysaccharides (LPS) stimulation in endometrial and vaginal cell lines. VK2 E6/E7 (vaginal) and KLE (epithelial) cell lines were stimulated with (1 × 10 to 5 × 10/mL) and LPS (1 μg/mL), respectively. Miodesin inhibited mRNA expression for Nuclear factor kappa B (NF-κB), ciclo-oxigenase 1 (COX-1), and phospholipase A2 (PLA2), beyond the C-C motif chemokine ligand 2 (CCL2), CCL3, and CCL5 in VK2 E6/E7 cells ( < 0.05). In addition, the inhibitory effects of both doses of Miodesin (10 µg/mL and 200 µg/mL) resulted in reduced secretion of interleukin-1β (IL-1β), IL-6, IL-8, tumor necrosis factor α (TNF-α) (24 h, 48 h, and 72 h) and CCL2, CCL3, and CLL5 ( < 0.05) by VK2 E6/E7 cells. In the same way, COX-1 Miodesin inhibited LPS-induced hyperactivation of KLE cells, as demonstrated by reduced secretion of IL-1β, IL-6, IL-8, TNF-α (24 h, 48 h, and 72 h) and CCL2, CCL3, and CLL5 ( < 0.05). Furthermore, Miodesin also inhibited mRNA expression and secretion of matrix metalloproteinase-2 (MMP-2), MMP-9, and vascular endothelial growth factor (VEGF), which are key regulators of invasion of endometrial cells. Thus, the study concludes that Miodesin presents beneficial effects in the context of endometriosis, positively affecting the inflammatory and proliferative response.
子宫内膜异位症的患病率很高，其病理生理学涉及子宫内膜和阴道细胞的过度激活，尤其是受细菌的影响。这种疾病目前无法治愈，因此非常需要开发旨在抑制其发展的治疗方法。因此，本研究旨在探讨米奥地辛（10μg/mL=IC；200μg/mL=IC），一种由β-胡萝卜素、叶黄素和虾青素组成的天然化合物，是否能抑制脂多糖（LPS）刺激子宫内膜和阴道细胞系的炎症和增殖反应。VK2 E6/E7（阴道）和 KLE（上皮）细胞系分别用（1×10 至 5×10/mL）和 LPS（1μg/mL）刺激。米奥地辛抑制了 VK2 E6/E7 细胞中核因子 kappa B（NF-κB）、环氧化酶 1（COX-1）和磷脂酶 A2（PLA2）的 mRNA 表达，还抑制了 C-C 基序趋化因子配体 2（CCL2）、CCL3 和 CCL5 的表达（<0.05）。此外，两种剂量的米奥地辛（10μg/mL 和 200μg/mL）均能减少白细胞介素-1β（IL-1β）、IL-6、IL-8、肿瘤坏死因子-α（TNF-α）（24 小时、48 小时和 72 小时）和 CCL2、CCL3 和 CCL5 的分泌（<0.05）。同样，米奥地辛也抑制了 LPS 诱导的 KLE 细胞过度激活，表现为白细胞介素-1β、IL-6、IL-8、TNF-α（24 小时、48 小时和 72 小时）和 CCL2、CCL3 和 CLL5 的分泌减少（<0.05）。此外，米奥地辛还抑制了基质金属蛋白酶-2（MMP-2）、MMP-9 和血管内皮生长因子（VEGF）的 mRNA 表达和分泌，这些都是子宫内膜细胞侵袭的关键调节因子。因此，本研究得出结论，米奥地辛对子宫内膜异位症具有有益的作用，能积极影响炎症和增殖反应。
