The Effect Flavonoids Phaleria macrocarpa Fruit Extract on Thickness of Trabeculae, Cortex Ratio Femoral Bone and Aortic Intima-Media in Mice Menopause Model


  • R. A. Rahmawati Nurul Fadilah Master Program of Midwifery, Department of Midwifery, Faculty of Medicine, Brawijaya University, Malang, East Java, Indonesia
  • Ani Khoirinda Master Program of Midwifery, Department of Midwifery, Faculty of Medicine, Brawijaya University, Malang, East Java, Indonesia
  • Sutrisno Sutrisno Department of Obstetric and Gynecology, Brawijaya University, Malang, East Java, Indonesia
  • Yahya Irwanto Department of Obstetric and Gynecology, Brawijaya University, Malang, East Java, Indonesia
  • Kenty Wantri Anita Department of Anatomical Pathology, Brawijaya University, Malang, East Java, Indonesia
  • R. A. Rose Khasana Dewi Department of Anatomical Pathology, Brawijaya University, Malang, East Java, Indonesia



Flavonoid, Phaleria macrocarpa, Menopause, Osteoporosis, Atherosclerosis


A deficiency of the hormone estrogen at menopause can lead to an increased rate of the destruction of the bone tissue that leads to bone loss, which can lead to osteoporosis and impaired fat metabolism, which increases the risk of atherosclerosis. Phytoestrogens from flavonoid extract P. Macrocarpa, having effects similar to endogenous estrogens themselves, prevent osteoporosis and atherosclerosis in menopausal women. The purpose of this research is to assess the influence of flavonoids from P. Macrocarpa fruit extract on trabeculae cortex thickness, ratio of femoral bone, and aortic IMT (A-IMT) in a menopausal mouse model. The study was conducted in a true experimental-posttest-only control group design. Using 32 mice; namely KN (normal mice with no treatment), KP (OVX with no treatment), P1(OVX and given flavonoid 3.75 mg/mice/day), P2 (OVX and given flavonoid 7.5 mg/mice/day), P3(OVX and given flavonoid 11.25 mg/mice/day), P4 (OVX and given flavonoid 15 mg/mice/day), the treatment given within 14 days. Then the thickness of the trabeculae, cortex, and intima-media aorta with Hematoxylin-Eosin (HE) staining. In the trabeculae, cortex thickness ratio obtained KN results meaningfully dissimilar to the KP group and the P3 and P4 groups were meaningfully dissimilar from the KP. The A-BMI in KP is meaningfully dissimilar to P1, P2, P3 and P4. The conclusion of the study is flavonoid fruit extract P. Macrocarpa can increase the thickness ratio of trabeculae, and cortex femoral bone of mice menopausal model in groups P3, P4 and can decrease A-IMT starting in groups P1 to P4.              


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Ahmad, R., Mazlan, M. K. N., Aziz, A. F. A., Gazzali, A. M., Rawa, M. S. A., & Wahab, H. A. (2023). Phaleria macrocarpa (Scheff.) Boerl.: An updated review of pharmacological effects, toxicity studies, and separation techniques. Saudi Pharmaceutical Journal, 31(6), 874-888.

Athiroh AS, N., & Permatasari, N. (2012). Mekanisme Kerja Benalu Teh pada Pembuluh Darah: Mechanism of Tea Mistletoe Action on Blood Vessels. Jurnal Kedokteran Brawijaya, 27(1), 1–7.

Bacciottini, L., Falchetti, A., Pampaloni, B., Bartolini, E., Carossino, A. M., & Brandi, M. L. (2007). Phytoestrogens: food or drug. Clin Cases Miner Bone Metab, 4(2), 123-130.

Biason-Lauber, A., & Lang-Muritano, M. (2022). Estrogens: Two nuclear receptors, multiple possibilities. Molecular and Cellular Endocrinology, 554(November 2020), 111710.

BPS, Bappenas dan UNFPA Indonesia. (2008). Proyeksi Penduduk Indonesia 2005-2025. Jakarta: BPS, Bappenas dan UNFPA Indonesia

de Villiers, T. J. (2023). Bone health and menopause: Osteoporosis prevention and treatment. Best Practice and Research: Clinical Endocrinology and Metabolism, 38(1), 101782.

Dumanauw, J. M., Minggus, R. E., Rintjap, D. S., Rumagit, B., & Maramis, R. N. (2022). Efek Farmakologi Tanaman Mahkota Dewa ( Phaleria Macrocarpa ( Scheff .) Boerl ) ( Studi Literatur ). E-Prosding Seminar Nasional Poltekkes Kemenkes Manado, 1(2), 157–167.

Erizon, E., & Karani, Y. (2020). HDL dan Aterosklerosis. Human Care Journal, 5(4), 11–23.

Fitriana, S., Andarini, S., Sutrisno, S., Nawangtantrini, G., & Maharani, M. (2023). Hepatotoxicity Oral Administration of Flavonoids Rich Extract from Phaleria Macrocarpha in Mice. Asian Journal of Health Research, 2(2), 36-41.

Forslund, L. C., & Andersson, H. C. (2017). Phytoestrogens in foods on the Nordic market: A literature review on occurrence and levels. Nordic Council of Ministers.

Geng, Q., Gao, H., Yang, R., Guo, K., & Miao, D. (2019). Pyrroloquinoline Quinone Prevents Estrogen Deficiency-Induced Osteoporosis by Inhibiting Oxidative Stress and Osteocyte Senescence. International journal of biological sciences, 15(1), 58–68.

Goo, Y. H. (2019). Cholesterol metabolism in atherosclerosis development. The Molecular Nutrition of Fats, 299–306.

Gosset, A., Pouillès, J. M., & Trémollieres, F. (2021). Menopausal hormone therapy for the management of osteoporosis. Best Practice & Research Clinical Endocrinology & Metabolism, 35(6), 101551.

Hasanah, M., Bahri, S., & Merta, I. W. (2020). Effect of Red Bean Extract (Phaseolus vulgaris, L) on the Development of Female Mice Eggs (Mus musculus) Balb/C strains. Jurnal Penelitian Pendidikan IPA, 6(2), 227-231.

Hopper, S. E., Cuomo, F., Ferruzzi, J., Burris, N. S., Roccabianca, S., Humphrey, J. D., & Figueroa, C. A. (2021). Comparative Study of Human and Murine Aortic Biomechanics and Hemodynamics in Vascular Aging. Frontiers in Physiology, 12(October), 1–14.

Huff, T., Boyd, B., & Jialal, I. (2021). Physiology, Cholesterol. Statpearls Publishing. Retrieved from

Javadifar, A., Rastgoo, S., Banach, M., Jamialahmadi, T., Johnston, T. P., & Sahebkar, A. (2021). Foam cells as therapeutic targets in atherosclerosis with a focus on the regulatory roles of non-coding RNAs. International Journal of Molecular Sciences, 22(5), 1–27.

Jebari-Benslaiman, S., Galicia-García, U., Larrea-Sebal, A., Olaetxea, J. R., Alloza, I., Vandenbroeck, K., Benito-Vicente, A., & Martín, C. (2022). Pathophysiology of Atherosclerosis. International Journal of Molecular Sciences, 23(6), 1–38.

Juwita, D. A., & Fatma, R. M. (2021). Effect of Propolis on Bone Quality and Cortical Bone Thickness of Ovariectomized Female Wistar White Rats as A Model for Osteoporosis. Pharmaceutical Sciences and Research, 8(3), 121–127.

Khatana, C., Saini, N. K., Chakrabarti, S., Saini, V., Sharma, A., Saini, R. V., & Saini, A. K. (2020). Mechanistic insights into the oxidized low‐density lipoprotein‐induced atherosclerosis. Oxidative medicine and cellular longevity, 2020(1), 5245308.

Khoudary, S. R., Venugopal, V., Manson, J. E., Brooks, M., Santoro, N., Black, D. M., Harman, M., Hodis, H. N., Brinton, E. A., Miller, V. M., Taylor, H. S., & Budoff, M. J. (2020). Heart Fat and Carotid Artery Atherosclerosis Progression in Recently Menopausal Women: Impact of Menopausal Hormone Therapy. The KEEPS Trial, 27(3), 255–262.

Kuhnle, G. G. C., Dell’Aquila, C., Aspinall, S. M., Runswick, S. A., Joosen, A. M. C. P., Mulligan, A. A., & Bingham, S. A. (2009). Phytoestrogen content of fruits and vegetables commonly consumed in the UK based on LC-MS and 13C-labelled standards. Food Chemistry, 116(2), 542–554.

Liu, X. (2020). Crucial molecular mechanisms of phytoestrogen regulation in osteoporosis. Front Endocrinol (Lausanne), 11(1), 608–634.

Macpherson, B. E., & Quinton, N. D. (2022). Menopause and healthcare professional education: A scoping review. Maturitas, 166(August), 89–95.

Maharani, M., Lajuna, L., Yuniwati, C., Sabrida, O., & Sutrisno, S. (2021). Phytochemical characteristics from Phaleria macrocarpa and its inhibitory activity on the peritoneal damage of endometriosis. Journal of Ayurveda and Integrative Medicine, 12(2), 229–233.

Maharani, & Sutrisno. (2021). Pengaruh Flavonoid Ekstrak Mahkota Dewa (Phaleria Macrocarpa) Terhadap Peningkatan Indeks Apoptosis Pada Peritoneal Mencit Model Endometriosis Abstract Effect of Flavonoid Extract From Mahkota Dewa (Phaleria Macrocarpa) on Increasing Cell Apoptotic Index . Jurnal Kebidanan Malahayati, 7(4), 652–657.

Mirza, D. M., Purbosari, I., Hardjono, S., & Agil, M. (2021). Prediksi Aktivitas Fitoestrogenik Senyawa Golongan Flavonoid terhadap Receptor Estrogen α (ER- α) dengan pendekatan In Silico Prediction. Jurnal Sains Dan Kesehatan, 3(4), 512–519.

Nayak, T., Freaney, P. M., & Maganti, K. (2022). Atherosclerotic Cardiovascular Disease Risk Assessment and Menopause: Current Evidence. American College of Cardiology.

Newson, L. (2018). Menopause and cardiovascular disease. Post Reproductive Health, 24(1), 44–49.

NIH. (2022). Structure of Bone Tissue. Seer Training Moduls Natioanal Institute of Health. Retrieved from

Pratiwi, M., & Damayanty, A. E. (2020). Pengaruh Pemberian Susu Kedelai (Glicine Max L. Merr) terhadap Kadar HDL dan LDL pada Wanita Menopause (Studi pada Ibu-Ibu Pengajian Aisyiyah Ranting Melati Medan). JURNAL ILMIAH KOHESI, 4(4), 132-137.

Pujiastuti, E., & El’Zeba, D. (2021). Perbandingan Kadar Flavonoid Total Ekstrak Etanol 70% dan 96% Kulit Buah Naga Merah Hylocereus Polyrhizus) dengan Spektrofotometri. Cendekia Journal of Pharmacy, 5(1), 28–43.

Rizalah, S., Hasan, M., & Wahyudi, S. S. (2016). Pengaruh Pemberian Kitosan Cangkang Udang Putih ( Penaeus merguiensis ) terhadap Ketebalan Trabekular Femur Tikus Wistar Betina Pasca Ovariektomi. E-Jurnal Pustaka Kesehatan, 4(1), 146–151.

Rochmah, K. (2008). Potensi Ekstrak Buah Mahkota Dewa (Phaleria macrocarpa) Sebagai Antioksidan Dalam Pengaturan Profil Lipid Darah Mencit. Jurnal Faal Indonesia, 7(3), 155–242.

Sadik, F., & Saiful Bachri, M. (2021). Uji Efektivitas Ekstrak Etanol Daun Jarak Pagar (Jatropha Curcas. L) Sebagai Antihipertensi Pada Tikus. Kieraha Medical Journal, 3(2), 2686–5912.

Sargowo, D. (2015). Disfungsi Endotel. UB Press.

Silva, T. R., Oppermann, K., Reis, F. M., & Spritzer, P. M. (2021). Review nutrition in menopausal women: A narrative review. Nutrients, 13(7), 1–14.

Stephenus, F. N., Benjamin, M. A. Z., Anuar, A., & Awang, M. A. (2023). Effect of Temperatures on Drying Kinetics, Extraction Yield, Phenolics, Flavonoids, and Antioxidant Activity of Phaleria macrocarpa (Scheff.) Boerl. (Mahkota Dewa) Fruits. Foods, 12(1), 1–19.

WHO. (2022). Menopause. World Health Organization.

Women Health Concern. (2021). Osteoporosis – Bone Health Following the Menopause. Women Health Concern.

Yousefzadeh, N., Kashfi, K., Jeddi, S., & Ghasemi, A. (2020). Ovariectomized rat model of osteoporosis: A practical guide. EXCLI Journal, 19, 89–107.




How to Cite

Fadilah, R. A. R. N., Khoirinda, A., Sutrisno, S., Irwanto, Y., Anita, K. W., & Dewi, R. A. R. K. (2024). The Effect Flavonoids Phaleria macrocarpa Fruit Extract on Thickness of Trabeculae, Cortex Ratio Femoral Bone and Aortic Intima-Media in Mice Menopause Model. JURNAL INFO KESEHATAN, 22(2), 307–316.



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