Ethanolic Extract of Papaya (Carica papaya) Leaf Exhibits Estrogenic Effects In Vivo and In Silico

Raisatun Nisa Sugiyanto, Rahmi Khamsita, Marvin Lambertus, Rohmad Yudi Utomo, Ratna Asmah Susidarti

Abstract


The menopause women have the low level of estrogen in the body. The lack of estrogen changes physiological function in women’s body that affects in health condition. Carica papaya L. leaf contains flavonoid quercetin which exhibits estrogenic effect. The aim of this study is to determine the estrogenic effect of papaya leaves extract (PLE) in vivo, and in silico. Papaya leaves were extracted by ethanol 70% maceration. The in silico study were done by molecular docking between quersetin and Estrogen Receptor (ERα and ERβ) to obtain the docking score. Based on this study, docking score of quercetin was almost similar to the native ligand of ER. The in vivo study was done as follow: 36 female rats Sprague Dawley divided into six groups.  The groups are shame-ovariectomized (S-OVX), control ovariectomized (OVX), CMC-Na control (OVX+CMC-Na), positive control (OVX+Estradiol), and the PLE treatment groups dose 750 mg/kgBW (OVX+750mg/kgBW) and dose 1000 mg/kgBW (OVX+1000 mg/kgBW). Administrations of PLE were done in three weeks orally, while estradiol was administrated intraperitonially. The mammae and uterine were sliced for analysis. Based on the study, the treatment of PLE increased the number of mammae lobules and uterine weight as well as estrogen does.  In summary, PLE can be developed as a source of phytoestrogens.

Keywords: Carica papaya L., phytoestrogen, estrogen receptor, mammae lobule, uterine


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References


Aouali, N., Morjani, H., Trussardi, A., Soma, E., Giroux, B. and Manfait, M., 2003, Enhanced Cytotoxicity and Nuclear Accumulation of Doxorubicin-loaded Nanospheres in Human Breast Cancer MCF-7 Cells Expressing MRP1, Int. J. Oncol., 23, 1195-1201. Link

Beral, V., Million Women Study Collaborators, 2003, Breast Cancer and Hormon Replacement Therapy in The Million Women Study, The Lancet, 362(9382), 413-427. Link

Bishop, T.C., Kosztin, D. and Schulten, K., 1997, How Hormone Receptor-DNA Binding Affects Nucleosomal DNA: The Role of Symmetry, Biophys. J., 72(5), 2056-2067. CrossRef

Canini, A., Alesiani, D., D’Arcangelo, G. and Tagliatesta, P., 2007, Gas Chromatography–Mass Spectrometry Analysis of Phenolic Compounds from Carica papaya L. leaf, J. Food Compost. Anal., 20(7), 584-590. CrossRef

Gnoni, G.V., Paglialonga, G. and Siculella, L., 2009, Quercetin Inhibits Fatty Acid and Triacylglycerol Synthesis In Rat-Liver Cells, Eur. J. Clin. Invest, 39(9), 761-768. CrossRef

Guyton, C.A., 1995, Fisiologi Manusia dan Mekanisme Penyakit. Terj. Human Physiology and mechanism of disease, by Petrus Andrianto. Jakarta: EGC.

Hess, R.A., 2003, Estrogen in The Adult Male Reproductive Tract: A Review., Reprod. Biol. Endocrinol., 1, 52. CrossRef

Jordan, V.C, 2004, Selective Estrogen Receptor Modulation: Concept and Consequences in Cancer, Cancer Cell, 5(3), 207-213. Link

Liu, J., Burdette, J.E., Xu, H., Gu, C., van Breemen, R.B., Bhat, K.P., et al., 2001, Evaluation of Estrogenic Activity of Plant Extracts for the Potential Treatment of Menopausal Symptoms, J. Agric. Food Chem., 49(5), 2472-2479. Link

Lodish, H., Berk, A., Zipursky, Lawrence, S., Matsurada, P. and Baltimore, D., 2000, Molecular Cell Biology, 4th Edition, New York: W.H. Freeman and Company. pp. 1052-1084.

Macville, M., Schröck, E., Padilla-Nash, H., Keck, C., Ghadimi, B.M., Zimonjic, D., et al., 1999, Comprehensive and Definitive Molecular Cytogenetic Characterization of HeLa Cells by Spectral Karyotyping, Cancer Res., 59(1), 141-150. Link

Martin, L., Finn, C. A. and Trinder, G., 1973, J. Endocrinol. 56, 133–144.

Mitchel, R.S., Kumar, V., Abbas, A.K., and Fautso, N., 2007, Robbins Basic Pathology: With Student Consult Online Access. Philadelphia: Saunders, p. 344. ISBN 1-4160-2973-7.8th edition.

Price, K. and Rhodes, M.J.C., 1997, Analysis of the Major Flavonol Glycosides Present in Four Varieties of Onion (Allium cepa) and Cchanges in Composition Resulting From Autolysis, J. Sci. Food Agric., 74(3), 331-339. CrossRef

Prunet, C., Lemaire-Ewing, S., Ménétrier, F., Néel, D. and Lizard, G., 2005, Activation of Caspase-3-Dependent and -Independent Pathways During 7-Ketocholesterol- and 7β-Hydroxycholesterol-Induced Cell Death: A Morphological and Biochemical Study, J. Biochem. Mol. Toxicol., 19(5), 311-326.

Rollerova, E. and Urbancikova M., 2000, Intracelullar Estrogen Receptors, Their Characterization and Function, Endocr. Regul., 34, 203-218. Link

Ruggiero, J. and Likis, F.E., 2002, Estrogen: Physiology, Pharmacology, and Formulations for Replacement Therapy, J. Midwifery Womens Health, 47(3), 130-138. Link

Schafer, J.M., Lee, E.S., O’Regan, R.M., Yao, K. and Jordan, V.C., 2000, Rapid Development of Tamoxifen-stimulated Mutant p53 Breast Tumors (T47D) in Athymic Mice, Clin. Cancer Res., 6(11), 4373-4380. Link

Stumpf, W. and Sar, M., 1976, in Receptors and Mechanism of Action of Steroid Hormones, ed. Pasqualini, J. Dekker, New York, 41–84.

Vallet, J.L. and Christenson, R.K., 2004, Effect of Progesterone, Mifepristone, and Estrogen Treatment During Early Pregnancy on Conceptus Development and Uterine Capacity in Swine, Biol. Reprod., 70(1), 92-98. CrossRef

Verma, S.P., Goldin, B.R. and Lin, P.S., 1998, The Inhibition of the Estrogenic Effects of Pesticides and Enviromental Chemicals by Curcumin and Isoflavonoids, Environ Health Perspect., 106(12), 807-812. Link




DOI: http://dx.doi.org/10.14499/indonesianjcanchemoprev3iss2pp384-390

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