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

Maharani Maharani, Sutrisno Sutrisno, Sri Winarsih, Agustina Tri Endharti, I Wayan Arsana Wıyasa, Husnul Khotimah, I Gde Budi Indrawan, Hendy Hendarto
In: Tropical Journal of Natural Product Research · 2025 · vol. 9(9) · doi:10.26538/tjnpr/v9i9.20 · W4414640301
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Phaleria macrocarpa extract reduced endometriosis lesions in mice by decreasing COX-2, NF-κB p65, VEGF-A, and Ki67 protein levels.

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The study evaluated the preventive potential of Phaleria macrocarpa mesocarp ethanol extract against endometriosis in a mouse model in which adenomyosis (ADM) tissue was implanted intraperitoneally under immunosuppression and supported with estradiol, with animals treated orally with multiple PM doses for 14 days. Using ELISA and immunohistochemistry, the investigators measured inflammation-related COX-2 and NF-κB p65 and assessed proliferation/angiogenesis markers VEGF-A and Ki67, along with ADM implant area. PM reduced COX-2 in a dose-dependent manner and inhibited NF-κB p65, VEGF-A, and Ki67 expression, resulting in a decreased ADM implant area. The paper’s limitation is that it uses a small-group animal design with short-term dosing and a specific induced model. This paper is centrally about endometriosis—testing Phaleria macrocarpa extract’s ability to prevent lesion development by regulating inflammatory proteins and inhibiting Ki67 and VEGF-A in an ADM/endo implant model that also includes adenomyosis tissue.

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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.   
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Phaleria Macrocarpa Extract Reduced Endometriosis Lesions by Regulating Inflammatory Protein and Inhibiting Ki67 and Vegf-A Protein DOI: https://doi.org/10.26538/tjnpr/v9i9.20Keywords: Phaleria macrocarpa, inflammation, Endometriosis, AdenomyosisAbstract 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. Downloads References Published Issue Section License Copyright (c) 2025 Tropical Journal of Natural Product Research This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

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endometriosisadenomyosisinfertility

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