The Combination of High Calcium Milk with Citrus maxima Peels Ethanolic Extract Increased Bone Density of Ovariectomized Rats

Ragil S. Dianingati, Annisa Novarina, Amanita K. Hana, Laeli Muntafi'ah, Endang Lukitaningsih


Osteoporosis is a common problem in menopause woman. The main cause is lack of estrogen hormone. Commonly, prevention therapy is by consuming high calcium milk, but it is not effective. Bali orange’s peel (Citrus maxima Merr.) is a waste material but known contains phytoestrogen according to previous study. Considering of this result, fortification of high calcium milk and Bali orange’s peel is expected to be an effective solution for osteoporosis in menopause woman. This research began with extraction of Bali orange’s peel (BPE) using ethanol 70% by maceration method. Ovariectomized Sprague Dawley female rats as the model of post menopausal woman were treated by BPE for 28 days. The doses of BPE was given to rats is 500 and 1000 mg/KgBW combined with high calcium milk. Bone density was determined using digital microradiography, the profile showed the increase of bone density in group that treated with combination of BPE 1000 mg/Kg BW and high calcium milk compare to control and given only milk groups. Docking molecular showed that BPE’s active compound which are hesperidin and naringin have interaction with estrogen receptor α and β. Docking score of naringin with ER α and β are -19,97; -18,99 respectively. Meanwhile the docking score of hesperidin with ER α and β are -19,98; +49,92 respectively. Overall, the result of this research showed that fortification of BPE with high calcium milk has good prospect to develop as effective therapy of osteoporosis.

Keywords : Citrus maxima Merr., phytoestrogen, osteoporosis, high calcium milk, estrogen receptor


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Arifin, Z., Hestiantoro, A. and Baziad, A., 2010, Pemberian Susu yang Difortifikasi Kalsium Kadar Tinggi dan Vitamin D dalam Memperbaiki Turn Over Tulang Perempuan Pascamenopause, Laporan Penelitian, Jakarta : Departemen Obstetri dan Ginekologi Fakultas Kedokteran Universitas Indonesia/RumahSakit Dr. Cipto Mangunkusumo.

Badan Pengawasan Obat dan Makanan, 2003, Pedoman Penilaian Label Pangan, Jakarta: BPOM.

Benassayag, C., Perrot-Applanat, M., and Ferre, F., 2002, Phytoestrogen as Modulators of Steroid Action in Target Cells, J. Chromatogr. B, 777(1-2), 233-248. CrossRef

CCRC, 2011, Efek Estrogenik Ekstrak Etanolik Kulit Buah Jeruk Bali (Citrus maxima Merr.) :Tinjauan Terhadap Bobot Uterus, Perkembangan Kelenjar Payudara, dan Ekspresi c-Myc pada Tikus Sprague Dawley Betina Terovariektomi, Unpublished data.

Choi, S.Y., Ko, H.C., Ko, S.Y., Hwang, J.H., Park, J.G., Kang, S.H., et al., 2007, Correlation between Flavonoid Content and the NO Production Inhibitory Activity of Peel Extracts from Various Citrus Fruits, Biol. Pharm. Bul, 30(4), 772-778. Link

Cornwell, T., Cohick, W. and Raskin, I., 2004, Dietary Phytoestrogens and Health, Phytochemistry, 65(8), 995-1016. CrossRef

Ikawati, Z., 2008, Pengantar Farmakologi Molekuler, Yogyakarta: Gama Press.

Kenny, A.M., Prestwood, K.M., Pilbeam, C.C. and Raisz, L.G., 2000, The Short Term Effects of Tamoxifen on Bone Turnover in Older Women, J. Clin. Endocrinol. Metab., 80(11), 3287-3291. CrossRef

Liliana, 2000, Metabolisme Kalsium dan Pencegahan Osteoporosis. di dalam eber Papyrus, Fakultas Kedokteran Universitas Tarumanegara, Jakarta.

Muirden, K.D., 1994, Osteoporosis Kumpulan Naskah WHO-COPCORD-IRA Post Graduate Course, Jakarta: WHO-COPCORD-IRA, 1-3.

Nadendla, R.R., 2004, Molecular Modeling: A Powerful Tool for Drug Design and Molecular Docking, Resonance, 9(5), 51-60. Link

Nordin, B.E., 2009, The Effect of Calcium Suplementation on Bone Loss in 32 Controlled Trials in Postmenopausal Women, Osteoporosis Int., 20(12), 2135-2143. CrossRef

Pacifici, R., 2006, Estrogen, Cytokines, and Pathogenesis of Postmenopausal Osteoporosis, J. Bone Miner. Res., 11(8), 1043-1051. CrossRef

Perry, S. and O’Hanlan, K.A., 2003, Natural Menopause, New York: Addison-Wesley Publishing Company.

Sankaran, B., 2000, Osteoporosis: Clinical, Radiological, Histological, Assesment and an Experimental Study, New Delhi: South East Asia Regional Office of the World Health Organisation.

Wagner, H., Bladt, S. and Zgainski, E.M., 1984, Plant Drug Analysis A Thin Layer Chromatography Atlas, Berlin: Springer Verlag.

Whitten, P.L. and Patisaul, H.B, 2001, Cross-Species and Interassay Comparisons of Phytoestrogen Action, Environ. Health Perspect., 109(Suppl.1), 5-20. Link

Yildiz, F., 2005, Phytoestrogens in Functional Foods, Boca Raton: CRC Press.


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