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. 2022 Jan 25;27(3):782.
doi: 10.3390/molecules27030782.

MiodesinTM Positively Modulates the Immune Response in Endometrial and Vaginal Cells

Affiliations

MiodesinTM Positively Modulates the Immune Response in Endometrial and Vaginal Cells

Carlos Rocha Oliveira et al. Molecules. .

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.

Keywords: MiodesinTM; anti-inflammatory; chemokines; endometriosis; leiomyoma.

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Conflict of interest statement

All authors disclose any influence of companies or manufacturers in the present study. In addition, all authors declare that the results of the study are presented clearly, honestly, and without fabrication, falsification, or inappropriate data manipulation.

Figures

Figure 1
Figure 1
Effects of MiodesinMT on endometrial (KLE) (A) and vaginal cell (VK2 E6/E7) (B) lines. Cells were treated with different concentrations of MiodesinMT for 24 h. The red dotted line represents the IC80 and IC50 point. The IC80 was defined as the study test concentration (10 µg/mL) while IC50 was defined as the study test concentration (200 µg/mL). Date shown are representative of three replicates in at least three independent experiments. * p < 0.05 indicates significant differences (ANOVA). Values are expressed as means ± SEM.
Figure 2
Figure 2
Effects of MiodesinTM (200 µg/mL and 10 µg/mL) on the expression of mRNA of NF-κβ, inflammatory enzymes and chemokines from endometrial (VK2 E6/E7) cells in presence or absence of LPS. (A) mRNA levels were significantly reduced (* p < 0.05) for NF-kβ, COX-1 and PLA2, except for COX-2 mRNA levels. (B) The mRNA levels of the chemokines CCL2/MCP-1, CCL3/MIP-1α, and CCL5/RANTES were significantly reduced. (C) mRNA levels were significantly reduced (* p < 0.05) for NF-kβ, COX-1, COX-2, and PLA2. (D) mRNA levels were significantly reduced (* p < 0.05) for CCL2, CCL3, and CCL5. mRNA levels were determined using real-time RT-PCR. Values are expressed as means ± SEM. (#) p < 0.05 LPS vs. control cells. (*) p < 0.05 MiodesinTM vs. LPS.
Figure 3
Figure 3
MiodesinMT regulates LPS-induced release of inflammatory cytokines. Endometrial cells (KLE cells) were pretreated with MiodesinTM (200 µg/mL and 10 µg/mL) for 2 h and treated with LPS (1 µg/mL) for 24 h. In subfigures (AD), the dose of MiodesinTM was 200ug/mL, and in subfigures (EH) the dose of MiodesinTM was 10ug/mL. The effect of MiodesinTM on decreasing release of interleukines evaluated was determined by ELISA. Values are expressed as means ± SEM. Values are expressed as means ± SEM. (#) p < 0.05 LPS vs. control (non-treated cells). (*) p < 0.05 MiodesinTM vs. LPS.
Figure 4
Figure 4
Effects of MiodesinTM (A), 200 µg/mL; (B), 10 µg/mL on the expression of mRNA of MMP-2, MMP-9, and VEGF in KLE cells. mRNA levels were significantly reduced for MMP-2, MMP-9, and VEGF. KLE cells were treated with MiodesinTM (200 µg/mL and 10 µg/mL) for 24 h. Real-time RT-PCR was performed to measure the mRNA levels of MMP-2, MMP-9, and VEGF in KLE cells. Glyceraldehyde-3-phosphate dehydrogenase (GADPH) was used as an internal control. Data are presented as the means ± SEM of three independent experiments. (*) p < 0.05.
Figure 5
Figure 5
Effects of MiodesinTM (200 µg/mL and 10 µg/mL) on the production of MMP2, MMP9, and VEGF. Following treatment with MiodesinTM (200 µg/mL) for 24 h. ELISA analysis was performed to determine the levels of MMP2 (A), MMP9 (B), and VEGF (C) in the cell culture supernatant. Data are presented as the means ± SEM of three independent experiments. (*) p < 0.05.

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