Korean J Physiol Pharmacol.  2018 Nov;22(6):627-636. 10.4196/kjpp.2018.22.6.627.

6-Shogaol reduces progression of experimental endometriosis in vivo and in vitro via regulation of VGEF and inhibition of COX-2 and PGE2-mediated inflammatory responses

• Wang D
• Jiang Y
• Yang X
• Wei Q
• Wang H

• KMID: 2430085
• DOI: http://doi.org/10.4196/kjpp.2018.22.6.627

Abstract

Endometriosis (EM) is one of the most common gynaecological disorder affecting women in their reproductive age. Mechanisms involved in the pathogenesis of EM remains poorly understood, however inflammatory responses have been reported to be significantly involved. The efficacy of 6-shogaol on proliferation of endometriotic lesions and inflammatory pathways in experimentally-induced EM model was explored in this study. EM was stimulated in Sprague-Dawley rats by implantation of autologous endometrium onto the peritoneum abdominal wall. Separate groups were treated with 6-shogaol (50, 100 or 150 mg/kg b.wt/day) via oral gavage for one month period. Gestrinone (GTN) group received GTN (0.5 mg/kg/day) as positive control. Five weeks after implantation, the spherical volume of ecto-uterine tissues was determined. Treatment with 6-shogaol significantly reduced the implant size. Histological analysis reported atrophy and regression of the lesions. 6-shogaol administration effectively down-regulated NF-κB signaling, VEGF and VEGFR-2 (Flk-1) expression in the endometriotic lesions. Excess production of IL-1β and IL-6 (pro-inflammatory cytokines), PGE2 and nitric oxide (NO) were reduced. Overall, the results of the study reveal the efficacy of 6-shogaol against endometriosis via effectively suppressing proliferation of the lesions and modulating angiogenesis and COX-2/NF-κB-mediated inflammatory cascades.

Keyword

6-Shogaol; Angiogenesis; Endometriosis; Inflammatory mediators; NF-κB

MeSH Terms

Abdominal Wall
Atrophy
Dinoprostone
Endometriosis*
Endometrium
Female
Gestrinone
Humans
In Vitro Techniques*
Interleukin-6
Nitric Oxide
Peritoneum
Rats, Sprague-Dawley
Vascular Endothelial Growth Factor A
Vascular Endothelial Growth Factor Receptor-2
Dinoprostone
Gestrinone
Interleukin-6
Nitric Oxide
Vascular Endothelial Growth Factor A
Vascular Endothelial Growth Factor Receptor-2

Figure

• 

  Fig. 1 Histopathological findings of endometriotic lesions following 6-shogaol treatment. 6-shogaol effectively caused regression of the lesions. (a) Representative photomicrograph presenting endometrotic lesions of EMS control group and (b) representative photomicrograph presenting regression and atrophy of lesions following 6-shogaol treatment at 150 mg/kg.

• 

  Fig. 2 6-Shogaol regulates the expression of VEGF and Flk-1. (a) 6-Shogaol markedly down-regulates the expressions of VEGF and Flk-1 mRNA levels. (b) Relative mRNA expression levels. Values are represented as mean±SD, n=6. p<0.05 as determined by one-way ANOVA followed by DMRT analysis. *Represents p<0.05 vs. control; #Represents p<0.05 vs. EMS control. a–dRepresents mean values from different experimental groups that differ from each other at p<0.05.

• 

  Fig. 3 Effect of 6-shogaol on VEGF and Flk-1 and COX-2 protein expressions. 6-Shogaol markedly regulates the expressions of VEGF and Flk-1 and COX-2 proteins (a). Representative immunoblot (b). Relative expressions of proteins. Values are represented as mean±SD, n=6. p<0.05 as determined by one-way ANOVA followed by DMRT analysis. Relative expressions of proteins from different experimental groups with control expressions set at 100%. *Represents p<0.05 vs. control; #Represents p<0.05 vs. EMS control. a–dRepresents mean values from different experimental groups that differ from each other at p<0.05.

• 

  Fig. 4 6-Shogaol down-regulated NF-κB signaling. 6-Shogaol significantly inhibited activation and regulated the inhibitor kinases of NF-κB signaling (a). Representative Immunoblot exhibiting the influence of 6-shogaol on the expressions of proteins (b and c). Relative expression of proteins. Values are represented as mean±SD, n=6. p<0.05 as determined by one-way ANOVA followed by DMRT analysis. Relative expressions of proteins from different experimental groups with control expressions set at 100%. *Represents p<0.05 vs. control; #Represents p<0.05 vs. EMS control. a–eRe presents mean values from different experimental groups that differ from each other at p<0.05.

• 

  Fig. 5 Effect of 6-Shogaol on inflammatory cytokines. 6-Shogaol reduced the levels of inflammatory cytokines (a) PGE2 (b) and NO (c). Values are represented as mean±SD, n=6. p<0.05 as determined by one-way ANOVA followed by DMRT analysis. Relative expressions of proteins from different experimental groups with control expressions set at 100%. *Represents p<0.05 vs. control; #Represents p<0.05 vs. EMS control. a–fRepresents mean values from different experimental groups that differ from each other at p<0.05.

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