Euterpe oleracea Extract (Açaí) Is a Promising Novel Pharmacological Therapeutic Treatment for Experimental Endometriosis.

Daniel Escorsim Machado,Karina Cristina Rodrigues-Baptista,Pergentino José Cunha Souza,Yasmin Marinho Da Silva,Kariny Gomes Pereira,Jessica Alessandra-Perini,Thiago Alves Dos Santos,Jamila Alessandra Perini,Roberto Soares De Moura,Luiz Eurico Nasciutti

doi:10.1371/journal.pone.0166059

Abstract

This study investigated the therapeutic potential of Euterpe oleracea extract (açaí) on the growth and survival of endometriotic lesions using an experimental model. Twenty female Sprague-Dawley rats were randomized into two groups after the implantation and establishment of autologous endometrium onto the peritoneum abdominal wall and treated with 200 mg/kg hydroalcoholic solution extract from açaí stone or vehicle via gastric tube for 30 consecutive days. Body weight, lesion surface areas, histological and immunohistochemistry analyses of vascular endothelial growth factor (VEGF), VEGF receptor-2 (VEGFR-2), metalloproteinase-9 (MMP-9), cyclooxygenase-2 (COX-2) and F4-80 were performed. Levels of VEGF, VEGFR-2, MMP-9 and COX-2 mRNA were measured. Flow cytometry of F4-80 was performed, and ELISA immunoassays measured prostaglandin E2 (PGE2), VEGF and nitric oxide (NO) and concentrations. Macrophage cell line J774.G8 was treated with 10, 20, and 40 μg/mL of açaí for 24, 48 and 72 h, and cell viability was measured using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays. Açaí treatment significantly decreased the implant size, and histological examination indicated atrophy and regression. A reduction in immunostaining and mRNA expression of VEGF, MMP-9 and COX-2 was observed, and F4-80 was lower in the treated group than the control group. The treated group also exhibited lower concentrations of PGE2, VEGF and NO compared to the control group. Macrophages cells treated with 20 and 40 μg/ml of açaí reduced cell viability in about 50% after 24, 48 and 72 h. Our results suggest that açaí effectively suppressed the establishment and growth of endometriotic lesions, and this agent is a promising novel pharmacological therapeutic treatment for endometriosis.

Highlights

Endometriosis is defined as the presence of functional endometrium outside the uterine cavity that consists of proliferating functional endometrial glands and stroma [1]
The angiogenesis process was investigated using mRNA expression, immunostaining and ELISA immunoassays based on MMP-9, vascular endothelial growth factor (VEGF) and its receptor VEGF receptor-2 (VEGFR-2) (S1 Table)
Our findings demonstrated that the presence of F4/80-positive macrophages and nitric oxide (NO) concentrations were higher in endometriotic lesions and statistically reduced in animals treated with acaı

Summary

Introduction

Endometriosis is defined as the presence of functional endometrium outside the uterine cavity that consists of proliferating functional endometrial glands and stroma [1]. It is an inflammatory disease associated with chronic pelvic pain and infertility, and it results in a markedly reduced quality of life [2]. The exact pathogenic mechanisms of endometriosis are not known, but several studies demonstrated that the development of a new vascular supply was essential for the establishment and growth of endometriotic lesions [4,5,6]. COX-2 and VEGF studies are associated with endometriosis and reinforce the hypothesis that the angiogenesis process and inflammation are crucial to the pathophysiology of this disease [8,11,12]

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Discussion

Conclusion