Phaleria macrocarpa Extract Reduced Endometriosis Lesions through Regulating Inflammatory Pathway, Inhibiting Ki67 and VEGF-A on Mice Model

Endometriosis is a complex and multifactorial disease causing severe pelvic pain, infertility, and reduced quality of life in women. Therefore, this study aimed to evaluate the preventive potential of Phaleria macrocarpa (PM) mesocarp ethanol extract on endometriosis. The animals used for the experiment were divided into eight groups, each comprising four mice. The first group served as control comprising healthy mice without PM treatment and adenomyosis (ADM) implantation. The second group was the control negative consisting of mice with ADM implantation and without PM treatment. The remaining six groups consisted of ADM mice treated with several doses of PM including 3.75, 7.5, 11.25, 15, 18.75, and 22.5 mg/kg/day orally for 14 days. On day 1 PM treatment, endometriosis was induced by implanting ADM tissue intraperitoneally in mice given an immunosuppressant, cyclosporin. Furthermore, mice were injected with estradiol intramuscularly (54 IU/mice) on the first and fifth day after ADM implantation. At day 15, the samples were sacrificed, endometriosis tissue was isolated to measure the implant area, and the ascites of peritoneal were collected to evaluate the level of Cyclooxygenase-2 (COX-2). The evaluation was performed using Enzyme-Linked Immunosorbent Assay (ELISA), and Nuclear Factor kappa-light-chain-enhancer of activated B cells p65 subunit (NF-κB p65), Vascular Endothelial Growth Factor A (VEGF-A), and Kiel-67 (Ki67) of peritoneal tissue expression level by immunohistochemistry. The results showed that PM could prevent inflammation and the development of endometriosis by reducing the level of COX-2 in a dose-dependent method. Additionally, PM extract inhibited the expression level of NF-κB p65, VEGF-A, and Ki67, reducing the ADM implant area.