Phaleria Macrocarpa Extract Reduced Endometriosis Lesions by Regulating Inflammatory Protein and Inhibiting Ki67 and Vegf-A Protein

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Maharani Maharani, Sutrisno Sutrisno, Sri Winarsih, Agustina Tri Endharti, I Wayan Arsana Wiyasa, Husnul Khotimah, I Wayan Agung Indrawan, Hendy Hendarto

2025 Tropical Journal of Natural Product Research Vol. 9 Issue 9 Article Cited by 1 Quartile

Abstract

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. © 2025 Maharani et al.

Affiliations

Doctoral Program in Medical Sciences, Faculty of Medicine, Universitas Brawijaya, East Java, Malang, Indonesia; Department of Midwifery, Polytechnic of Health-Ministry of Health, Aceh, Indonesia; Department of Obstetrics and Gynaecology, Faculty of Medicine, Universitas Brawijaya/ Saiful Anwar General Hospital, East Java, Malang, Indonesia; Magister of Midwifery, Faculty of Medicine, Universitas Brawijaya, East Java, Malang, Indonesia; Pharmacy Study Program, Faculty of Medicine, Universitas Brawijaya, East Java, Malang, Indonesia; Department of Parasitology, Faculty of Medicine, Universitas Brawijaya, East Java, Malang, Indonesia; Biomedical Central Laboratory Faculty of Medicine, Universitas Brawijaya, East Java, Malang, Indonesia; Department of Pharmacology, Faculty of Medicine, Universitas Brawijaya, East Java, Malang, Indonesia; Department of Obstetric Gynecology, Faculty of Medicine, Universitas Airlangga, Surabaya, Indonesia