Therapeutic Potential of Phaleria Macrocarpa Flavonoid Extract Regulating Rantes in Endometriosis

Endometriosis is a long-term inflammatory disease that affects women of childbearing age. It is caused by endometrial tissue growing in places other than the uterus. RANTES (Regulated on Activation, Normal T Cell Expressed and Secreted) and other important inflammatory mediators are very important in making the inflammatory responses related to this disorder worse. The aim of this study was to evaluate the impact of the ethanolic extract of flavonoids derived from the fruit of Phaleria macrocarpa (Mahkota Dewa) on RANTES levels in a rat model of endometriosis. Thirty female rats were divided into six groups: one healthy control group, one endometriosis control group, and four treatment groups that received doses of 3.75, 7.5, 15, and 30 mg/rat/day of the extract, respectively. The endometriosis model was established by transplanting myometrial and endometrial tissues from a patient with adenomyosis into the peritoneal cavity of immunosuppressed rats. Once the model was set up, the rats got the extract every day for 15 days in a row. We used the ELISA method to measure RANTES levels and histological and immunohistochemical analyses to look at ERβ expression. The results showed that the endometriosis control group (K+) had the highest levels of RANTES (64.05 ? 1.86 pg/mL). Surprisingly, the group that got 30 mg/rat/day (P4) had the biggest drop in RANTES levels (45.95 ? 1.07 pg/mL). Moreover, an upregulation of ERβ expression was observed in rats with induced endometriosis, evidenced by intensified brown staining, succeeded by a dose-dependent reduction, signifying modulation of estrogenic activity. In summary, the administration of the ethanolic flavonoid extract from Phaleria macrocarpa significantly reduced RANTES levels in rats with endometriosis, underscoring its potential as an alternative treatment for managing inflammation related to endometriosis. ?

Keywords: Phaleria macrocarpa, flavonoid, endometriosis, RANTESFull Text: PDFReferences Abd Gani, S. S., Noor Ezzuddin, N. N., Zaidan, U. H., Halmi, M. I. E., & Abd Halim, A. N. (2023). Flavonoid Content of Phaleria macrocarpa Fruit and Its Proximate Compositions. Malaysian Applied Biology, 52(4), 119?125. https://doi.org/10.55230/mabjournal.v52i4.m024 Ahmad, R., Mazlan, M., Aziz, A., Gazzali, A., & ... (2023). Phaleria macrocarpa (Scheff.) Boerl.: An updated review of pharmacological effects, toxicity studies, and separation techniques. Saudi Pharmaceutical ?, Query date: 2024-10-31 09:06:40. https://www.sciencedirect.com/science/article/pii/S1319016423000889 Annissa Febriani, Sutrisno, S., Yahya Irwanto, Irfani Baihaqi, I Wayan Arsana Wiyasa, & Bambang Rahardjo. (2022). Effect of Phaleria macrocarpa Extract on NF-KB, MMP-2, and MMP-9 Expression in Endometriosis Mice Model. Asian Journal of Health Research, 1(3). https://doi.org/10.55561/ajhr.v1i3.35 Arba, M., Aslikah, N., & Yanuar, A. (n.d.). Insight on Estrogen Receptor Alpha Modulator from Indonesian Herbal Database: An in-silico analysis. Pharmaceutical Journal of Indonesia, 02. Brun, C., Moulin, F., Leboube, S., Hayek, A., Kaczmarczyk, A., Saleh, I. A., Prieur, C., Varillon, Y., Bonnefoy‐Cudraz, E., Mewton, N. O., Bidaux, G., Crola Da Silva, C., Paillard, M., Ducreux, S., & Bochaton, T. (2024). Kinetics and Prognosis Value of CCL5/RANTES at the Acute Phase of ST‐Segment?Elevation Myocardial Infarction. Journal of the American Heart Association, 13(19), e033110. https://doi.org/10.1161/JAHA.123.033110 Chiu, K.-L., & Wang, I.-T. (2024). Endometriosis, pregnancy and delivery complications: Evidence from the US nationwide inpatient sample 2005?2018. Taiwanese Journal of Obstetrics and Gynecology, 63(3), 350?356. https://doi.org/10.1016/j.tjog.2023.06.005 Dinata, D. I., Muttaqin, F. Z., Sodik, J. J., Irfani, A. M., & Binawan, Y. N. (2025). In Silico Study of Flavonoid Derivative Compounds against ER-α as. 12. Febriani, A., Sutrisno, S., Irwanto, Y., Baihaqi, I., & ... (2022). Effect of Phaleria macrocarpa Extract on NF-KB, MMP-2, and MMP-9 Expression in Endometriosis Mice Model. Asian Journal of Health ?, Query date: 2024-10-31 09:06:40. https://www.a-jhr.com/a-jhr/article/view/35 Gordts, S., Koninckx, P., & Brosens, I. (2017). Pathogenesis of deep endometriosis. Fertility and Sterility, 108(6), 872-885.e1. https://doi.org/10.1016/j.fertnstert.2017.08.036 Guo, S.-W. (2020). The Pathogenesis of Adenomyosis vis-?-vis Endometriosis. Journal of Clinical Medicine, 9(2), 485. https://doi.org/10.3390/jcm9020485 Habiba, M., Benagiano, G., & Guo, S.-W. (2023). An Appraisal of the Tissue Injury and Repair (TIAR) Theory on the Pathogenesis of Endometriosis and Adenomyosis. Biomolecules, 13(6), 975. https://doi.org/10.3390/biom13060975 Ikhtiarudin, I., Dona, R., Frimayanti, N., Utami, R., Susianti, N., & Septama, A. W. (2022). Sintesis, Karakterisasi Struktur, dan Kajian Molecular Docking Senyawa Turunan 4?-Metoksi Flavonol sebagai Antagonis Reseptor Estrogen Alpha (ER-a) pada Kanker Payudara. Jurnal Riset Kimia, 13(2), 236?249. https://doi.org/10.25077/jrk.v13i2.553 Kusmardi, K., Situmorang, N. Y., Zuraidah, E., Estuningtyas, A., & Tedjo, A. (2021). The Effect of Mahkota Dewa (Phaleria macrocarpa) Leaf Extract on the Mucin 1 Expression in Mice Colonic Epithelial Cells Induced by Dextran Sodium Sulfate (DSS). Pharmacognosy Journal, 13(6), 1509?1515. https://doi.org/10.5530/pj.2021.13.192 Li, N., Mirzakhani, H., Kiefer, A., Koelle, J., Vuorinen, T., Rauh, M., Yang, Z., Krammer, S., Xepapadaki, P., Lewandowska-Polak, A., Lukkarinen, H., Zhang, N., Stanic, B., Zimmermann, T., Kowalski, M. L., Jartti, T., Bachert, C., Akdis, M., Papadopoulos, N. G., ? Finotto, S. (2021). Regulated on Activation, Normal T cell Expressed and Secreted (RANTES) drives the resolution of allergic asthma. iScience, 24(10), 103163. https://doi.org/10.1016/j.isci.2021.103163 Liu, X., Shen, M., Qi, Q., Zhang, H., & Guo, S.-W. (2016). Corroborating evidence for platelet-induced epithelial-mesenchymal transition and fibroblast-to-myofibroblast transdifferentiation in the development of adenomyosis. Human Reproduction, 31(4), 734?749. https://doi.org/10.1093/humrep/dew018 Maharani, M., Lajuna, L., Yuniwati, C., Sabrida, O., & ... (2021). Phytochemical characteristics from Phaleria macrocarpa and its inhibitory activity on the peritoneal damage of endometriosis. Journal of Ayurveda and ?, Query date: 2024-10-31 09:06:40. https://www.sciencedirect.com/science/article/pii/S0975947619303092 Maharani, M., & Sutrisno, S. (2022). Phaleria macrocarpa Flavonoid as a Potent MMP-1 Inhibitor for Endometriosis Therapy: In silico Study. Asian Journal of Health Research, Query date: 2024-10-31 09:06:40. https://www.a-jhr.com/a-jhr/article/view/24 Petraglia, F., Vannuccini, S., Santulli, P., Marcellin, L., & Chapron, C. (2024). An update for endometriosis management: A position statement. Journal of Endometriosis and Uterine Disorders, 6, 100062. https://doi.org/10.1016/j.jeud.2024.100062 Polari, L., Wiklund, A., Sousa, S., Kangas, L., Linnanen, T., H?rk?nen, P., & M??tt?, J. (2018). SERMs Promote Anti-Inflammatory Signaling and Phenotype of CD14+ Cells. Inflammation, 41(4), 1157?1171. https://doi.org/10.1007/s10753-018-0763-1 Salinah, S., Kodariah, R., & Wuyung, P. E. (2020). Peranan Gen HOXA10 terhadap Infertilitas Terkait Endometriosis. Jurnal Kedokteran dan Kesehatan Publikasi Ilmiah Fakultas Kedokteran Universitas Sriwijaya, 7(1), 23?31. https://doi.org/10.32539/JKK.V7I1.8294 Saunders, P. T. K., & Horne, A. W. (2021). Endometriosis: Etiology, pathobiology, and therapeutic prospects. Cell, 184(11), 2807?2824. https://doi.org/10.1016/j.cell.2021.04.041 Smolarz, B., Szyłło, K., & Romanowicz, H. (2021). Endometriosis: Epidemiology, Classification, Pathogenesis, Treatment and Genetics (Review of Literature). International Journal of Molecular Sciences, 22(19), 10554. https://doi.org/10.3390/ijms221910554 Sutrisno, S., Andarini, S., Wiyasa, I. W. A., Kulsum, U., Noerhamdani, N., Suyuti, H., & Hendarto, H. (2018). The Effect of Implant Origin Differences on Peritoneal Endometriosis in an Endometriosis Mouse Model. International Journal of Women?s Health and Reproduction Sciences, 7(1), 34?40. https://doi.org/10.15296/ijwhr.2019.06 Vacaroiu, I. A., Balcangiu-Stroescu, A.-E., Stanescu-Spinu, I.-I., Balan, D. G., Georgescu, M.-T., Greabu, M., Miricescu, D., Cuiban, E., Șerban-Feier, L. F., Lupușoru, M. O. D., Gaube, A., & Georgescu, D.-E. (2023). Chronic Pelvic Puzzle: Navigating Deep Endometriosis with Renal Complications. Journal of Clinical Medicine, 13(1), 220. https://doi.org/10.3390/jcm13010220 Zhang, T., Ma, C., Zhang, Z., Zhang, H., & Hu, H. (2021). NF‐κB signaling in inflammation and cancer. MedComm, 2(4), 618?653. https://doi.org/10.1002/mco2.104 DOI: http://dx.doi.org/10.30829/contagion.v7i3.25587 Refbacks - There are currently no refbacks. Copyright (c) 2026 Fany Hardiati Amalia, Amina Diarsy, Sutrisno Sutrisno, Safrina Dewi Ratnaningrum This work is licensed under a Creative Commons Attribution-ShareAlike 4.0 International License.