MiodesinTM Positively Modulates the Immune Response in Endometrial and Vaginal Cells.

Carlos Rocha Oliveira,Hudson Polonini,Maria Cristina Marcucci,Rodolfo P Vieira

doi:10.3390/molecules27030782

Abstract

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 MiodesinTM (10 µg/mL = IC80; 200 µg/mL = IC50), a natural compound constituted by Uncaria tomentosa, Endopleura uchi, and astaxanthin, could exert anti-inflammatory and anti-proliferative effects against Lipopolysaccharides (LPS) stimulation in endometrial and Candida albicans vaginal cell lines. VK2 E6/E7 (vaginal) and KLE (epithelial) cell lines were stimulated with Candida albicans (1 × 107 to 5 × 107/mL) and LPS (1 μg/mL), respectively. MiodesinTM 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 (p < 0.05). In addition, the inhibitory effects of both doses of MiodesinTM (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 (p < 0.05) by VK2 E6/E7 cells. In the same way, COX-1 MiodesinTM 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 (p < 0.05). Furthermore, MiodesinTM 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 MiodesinTM presents beneficial effects in the context of endometriosis, positively affecting the inflammatory and proliferative response.

Highlights

Endometriosis is estimated to affect around 10% of the female population in reproductive age, reaching 20–90% in those with pelvic pain and/or infertility
These events are essential for induction of endometrial lesions in the peritoneal cavity, which have a key role of matrix metalloproteinase (MMP), such as matrix metalloproteinase2 (MMP-2) [4], MMP-9 [5], and vascular endothelial growth factor (VEGF) [6]
We investigated the effects of MiodesinTM (10 μg/mL and 200 μg/mL) on the mRNA expression of transcription factor, inflammatory mediators, and chemokines in VK2 E6/E7 cells

Summary

Introduction

Endometriosis is estimated to affect around 10% of the female population in reproductive age, reaching 20–90% in those with pelvic pain and/or infertility. Many patients report changes in quality of life, mainly due to pain and emotional problems related to infertility, among other factors [1] This condition can be understood as a chronic and estrogen-dependent disease, characterized by the growth of endometrial tissue outside of the uterine cavity. The pro-inflammatory cascade in endometriosis triggers changes in cell proliferation, adhesion, and migration of endometrial tissue, which are fundamental for the success of ectopic implantation [3] These events are essential for induction of endometrial lesions in the peritoneal cavity, which have a key role of matrix metalloproteinase (MMP), such as MMP-2 [4], MMP-9 [5], and VEGF [6]. A group of researchers demonstrated increased expression of PLA2 in endometriotic ovarian cysts and positive correlations with the progesterone receptor (PR-B) and estrogen receptor (Erβ) [10]

Methods

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Discussion

Conclusion