Ethanol Extract of Carica papaya Leaf Can Increase Breast Milk in Lactating Rat
DOI:
https://doi.org/10.3889/oamjms.2021.6529Keywords:
Carica papaya leaves, Galactogogue, Prolactin, Prolactin receptor, Breast alveoli, LobesAbstract
BACKGROUND: Carica papaya leaves (Carica papaya L) have been used empirically and traditionally as a galactogogue, but their mechanism as galactogogue is still unknown.
AIM: This study aimed to analyze the effect of ethanol extract from papaya leaves on blood prolactin levels, prolactin receptor (prlr) gene expression, the number of breast alveoli and lobes of lactating rats.
METHODS: This in vivo true experimental study with a post-test control group design was conducted on 24 rats with the same lactating period. They were divided into four groups consisting of six rats each. The control group was given daily standard food, whereas the three treatment groups were, respectively, given additionally ethanol extract of 0.95 mg, 1.9 mg, and 3.8 mg/200 g BW/day from day 1 to day 14 of lactation. On day 14, all of the rats were sacrificed, blood prolactin levels were measured by ELISA, prlr gene expressions were measured using RT-PCR, and numbers of breast alveoli and lobes were microscopically observed through staining histological specimens. A statistical analysis was carried out using one-way ANOVA, Tukey's test, Games–Howell test, and path analysis at 95% confidence level.
RESULTS: Levels of blood prolactin levels, prlr gene expression, the number of breast alveoli, and lobes of all treatment rat groups were significantly above those of the control group (p < 0.05). The increases of all parameters were consistent; the most effective dose was 1.9 mg/200 g BW.
CONCLUSION: The Carica papaya leaf ethanol extract had a galactogogue effect on lactating rats by increasing blood prolactin levels, prlr gene expression, and numbers number of breast alveoli and lobes.
Downloads
Metrics
Plum Analytics Artifact Widget Block
References
Andreas NJ, Kampmann B, Le-Doare KM. Human breast milk: A review on its composition and bioactivity. Early Hum Dev. 2015;91(11):629-35. https://doi.org/10.1016/j.earlhumdev.2015.08.013 PMid:26375355 DOI: https://doi.org/10.1016/j.earlhumdev.2015.08.013
Feng P, Gao M, Burgher A, Zhou TH, Pramuk K. A nine-country study of the protein content and amino acid composition of mature human milk. Food Nutr Res. 2016;60(1):31042. https://doi.org/10.3402/fnr.v60.31042 PMid:27569428 DOI: https://doi.org/10.3402/fnr.v60.31042
Lessen R, Kavanagh K. Position of the academy of nutrition and dietetics: Promoting and supporting breastfeeding. J Acad Nutr Diet. 2015;115(3):444-9. https://doi.org/10.1016/j.jand.2014.12.014 PMid:25721389 DOI: https://doi.org/10.1016/j.jand.2014.12.014
Cadwell K, Turner C. Manajemen Laktasi [Lactation Management]. Jakarta: EGC; 2011.
Ballard O, Morrow AL. Human milk composition: Nutrients and bioactive factors. Boreal Environ Res. 2013;60(1):49-74. PMid:23178060 DOI: https://doi.org/10.1016/j.pcl.2012.10.002
Piwoz EG, Huffman SL. The impact of marketing of breast-milk substitutes on WHO-recommended breastfeeding practices. Food Nutr Bull. 2015;36(4):373-86. https://doi.org/10.1177/0379572115602174 PMid:26314734 DOI: https://doi.org/10.1177/0379572115602174
Grzeskowiak LE, Wlodek ME, Geddes DT. What evidence do we have for pharmaceutical galactagogues in the treatment of lactation insufficiency?-A narrative review. Nutrients. 2019;11(5):974. https://doi.org/10.3390/nu11050974 PMid:31035376 DOI: https://doi.org/10.3390/nu11050974
Wambach K, Riordan J. Breastfeeding and Human Lactation. USA: Jones and Bartlett Publishers; 2005. p. 6-162.
Lawrence RA, Lawrence RM. Breastfeeding: A Guide for the Medical Profession. Missouri, TX: Elsevier Publisher; 2011.
Al-Chalabi M, Bass AN, Alsalman I. Physiology, prolactin. In: Stat Pearls. Treasure Island, FL: Stat Pearls Publishing; 2021.
Nilsson L. Effects of Prolactin on Metabolism. Sweden: Department of Physiology, University of Gothenburg; 2009.
Kim YJ. Pivotal roles of prolactin and other hormones in lactogenesis and the nutritional composition of human milk. Clin Exp Pediatr. 2020;63(8):312-3. https://doi.org/10.3345/cep.2020.00311 PMid:32746532 DOI: https://doi.org/10.3345/cep.2020.00311
Radhakrishnan A, Raju R, Tuladhar N, Subbannayya T, Thomas JK, Goel R, et al. A pathway map of prolactin signaling. J Cell Commun Signal. 2012;6(3):169-73. PMid:22684822 DOI: https://doi.org/10.1007/s12079-012-0168-0
Liu F, Pawliwec A, Feng Z, Yasruel Z, Lebrun JJ, Ali S. Prolactin/ Jak2 directs apical/basal polarization and luminal linage maturation of mammary epithelial cells through regulation of the Erk1/2 pathway. Stem Cell Res. 2015;15(2):376-83. https://doi.org/10.1016/j.scr.2015.08.001 PMid:26318719 DOI: https://doi.org/10.1016/j.scr.2015.08.001
Melmed S, Conn PM. Endocrinology: Basic and Clinical Principles. Totowa, NJ: Springer Science and Business Media; 2007.
Brooks CL. Molecular mechanisms of prolactin and its receptor. Endocr Rev. 2012;33(4):504-25. PMid:22577091 DOI: https://doi.org/10.1210/er.2011-1040
Bazzano AN, Hofer R, Thibeau S, Gillispie V, Jacobs M, Theall KP. A review of herbal and pharmaceutical galactagogues for breast-feeding. Ochsner J. 2016;16(4):511-24. PMid:27999511
Srinivas R, Eagappan K, Sasikumar S. The effect of naturally formulated galactagogue mix on breast milk production, prolactin level and short-term catch-up of birth weight in the first week of life. Int J Health Sci Res. 2014;4(10):242-53.
Hill PD, Aldag JC, Demirtas H, Naeem V, Parker NP, Zinaman MJ, et al. Association of serum prolactin and oxytocin with milk production in mothers of preterm and term infants. Biol Res Nurs. 2009;10(4):340-9. https://doi.org/10.1177/1099800409331394 PMid:19224938 DOI: https://doi.org/10.1177/1099800409331394
Zuppa AA, Sindico P, Orchi C, Carducci C, Cardiello V, Romagnoli C, et al. Safety and efficacy of galactogogues: Substances that induce, maintain and increase breast milk production. J Pharm Pharm Sci. 2010;13(2):162-74. https://doi.org/10.18433/j3ds3r PMid:20816003 DOI: https://doi.org/10.18433/J3DS3R
Tabares FP, Jaramillo JV, Ruiz-Cortés ZT. Pharmacological overview of galactogogues. Vet Med Int. 2014;2014:602894. PMid:25254141 DOI: https://doi.org/10.1155/2014/602894
Seigler DS, Pauli GF, Nahrstedt A, Leen R. Cyanogenic allosides and glucosides from Passiflora edulis and Carica papaya. Phytochemistry. 2002;60(8):873-82. https://doi.org/10.1016/s0031-9422(02)00170-x PMid:12150815 DOI: https://doi.org/10.1016/S0031-9422(02)00170-X
Ikram EHK, Stanley R, Netzel M, Fanning K. Phytochemicals of papaya and its traditional health and culinary uses-a review. J Food Compos Anal. 2015;41:201-11. https://doi.org/10.1016/j.jfca.2015.02.010 DOI: https://doi.org/10.1016/j.jfca.2015.02.010
Miean KH, Mohamed S. Flavonoid (myricetin, quercetin, kaempferol, luteolin, and apigenin) content of edible tropical plants. J Agric Food Chem. 2001;49(6):3106-12. https://doi.org/10.1021/jf000892m PMid:11410016 DOI: https://doi.org/10.1021/jf000892m
Sardjono TW, Gondo HK, Nugraha RY, Putri AT, Effendy MC. The use of natural phenomenon in obtaining pregnant rats and mice as experimental animals with the same gestational ages. J Trop Life Sci. 2019;9(3):229-35. https://doi.org/10.11594/ jtls.09.03.03 DOI: https://doi.org/10.11594/jtls.09.03.03
Zhang QW, Lin LG, Ye WC. Techniques for extraction and isolation of natural products: A comprehensive review. Chin Med. 2018;13(1):20. PMid:29692864 DOI: https://doi.org/10.1186/s13020-018-0177-x
Imaga NA, Gbenle GO, Okochi VI, Adenekan S, Duro- Emmanuel T, Oyeniyi B, et al. Phytochemical and antioxidant nutrient constituents of Carica papaya and Parquetina nigrescens extracts. Sci Res Essays. 2010;5(16):2201-5.
Mohanty I, Senapati MR, Jena D, Behera PC. Ethnoveterinary importance of herbal galactogogues-a review. Vet World. 2014;7(5):325-30. https://doi.org/10.14202/vetworld.2014.325-330 DOI: https://doi.org/10.14202/vetworld.2014.325-330
Yakubu MT, Akanji MA, Oladiji AT, Olatinwo AO, Adesokan AA, Yakubu MO, et al. Effect of Cnidoscolous aconitifolius (Miller) I. M. Johnston leaf extract on reproductive hormones of female rats. Iran J Reprod Med. 2008;6(3):149-55.
Calabrese EJ, Bachmann KA, Bailer AJ, Bolger PM, Borak J, Cai L, et al. Biological stress response terminology: Integrating the concepts of adaptive response and preconditioning stress within a hormetic dose-response framework. Toxicol Appl Pharmacol. 2007;222(1):122-8. PMid:17459441
Holst B, Williamson G. Nutrients and phytochemicals: From bioavailability to bioefficacy beyond antioxidants. Curr Opin Biotechnol. 2008;19(2):73-82. https://doi.org/10.1016/j.copbio.2008.03.003 PMid:18406129 DOI: https://doi.org/10.1016/j.copbio.2008.03.003
Alseekh S, de Souza LP, Benina M, Fernie AR. The style and substance of plant flavonoid decoration; towards defining both structure and function. Phytochemistry. 2020;174:112347. https://doi.org/10.1016/j.phytochem.2020.112347 PMid:32203741 DOI: https://doi.org/10.1016/j.phytochem.2020.112347
Salahshoor MR, Mohammadi MM, Roshankhah S, Jalili C. Effect of Falcaria vulgaris on milk production parameters in female rats’ mammary glands. J Family Reprod Health. 2018;12(4):177-83. PMid:31239844
Canini A, Alesiani D, D’Arcangelo G, Tagliatesta P. Gas chromatography-mass spectrometry analysis of phenolic compounds from Carica papaya L. leaf. J Food Compos Anal. 2007;20(7):584-90. https://doi.org/10.1016/j.jfca.2007.03.009 DOI: https://doi.org/10.1016/j.jfca.2007.03.009
Suresh K, Deepa P, Harisaranraj R, Vaira AV. Antimicrobial and phytochemical investigation of the leaves of Carica papaya L., Cynodon dactylon (L.) Pers., Euphorbia hirta L., Melia azedarach L. and Psidium guajava L. Ethnobot Leafl. 2008;12:1184-91.
Duke J. Phytochemical and Ethnobotanical Database; 2011. Available from: http//www.sun.ars-grin.gov:8080/npgspub/xsql/duke/plantdisp.xsql?taxon=209. [Last accessed on 2017 Sep 05].
Lin M, Wang N, Yao B, Zhong Y, Lin Y, You T. Quercetin improves postpartum hypogalactia in milk-deficient mice via stimulating prolactin production in pituitary gland. Phytother Res. 2018;32(8):1511-20. https://doi.org/10.1002/ptr.6079 PMid:29671937 DOI: https://doi.org/10.1002/ptr.6079
Haschke F, Haiden N, Thakkar SK. Nutritive and bioactive proteins in breastmilk. Ann Nutr Metab. 2017;69 Suppl 2:17-26. https://doi.org/10.1159/000452820 PMid:28103610 DOI: https://doi.org/10.1159/000452820
Alok S, Jain SK, Verma A, Kumar M, Mahor A, Sabharwal M. Plant profile, phytochemistry and pharmacology of Asparagus racemosus (Shatavari): A review. Asian Pac J Trop Dis. 2013;3(3):242-51. https://doi.org/10.1016/s2222-1808(13)60049-3 DOI: https://doi.org/10.1016/S2222-1808(13)60049-3
Badgujar SB, Patel VV, Bandivdekar AH. Foeniculum vulgare Mill: A review of its botany, phytochemistry, pharmacology, contemporary application, and toxicology. Biomed Res Int. 2014;2014:842674. https://doi.org/10.1155/2014/842674 PMid:25162032 DOI: https://doi.org/10.1155/2014/842674
Paikra BK, Dhongade HK, Gidwani B. Phytochemistry and pharmacology of Moringa oleifera Lam. J Pharmacopuncture. 2017;20(3):194-200. https://doi.org/10.3831/kpi.2017.20.022 PMid:30087795 DOI: https://doi.org/10.3831/KPI.2017.20.022
Augustine RA, Kokay IC, Andrews ZB, Ladyman SR, Grattan DR. Quantitation of prolactin receptor mRNA in the maternal rat brain during pregnancy and lactation. J Mol Endocrinol. 2003;31(1):221-32. https://doi.org/10.1677/jme.0.0310221 PMid:12914538 DOI: https://doi.org/10.1677/jme.0.0310221
Gass S, Harris J, Ormandy C, Brisken C. Using gene expression arrays to elucidate transcriptional profiles underlying prolactin function. J Mammary Gland Biol Neoplasia. 2003;8(3):269-85. https://doi.org/10.1023/b:jomg.0000010029.85796.63 PMid:14973373 DOI: https://doi.org/10.1023/B:JOMG.0000010029.85796.63
Gorvin CM. The prolactin receptor: Diverse and emerging roles in pathophysiology. J Clin Transl Endocrinol. 2015;2(3):85-91. PMid:29204371 DOI: https://doi.org/10.1016/j.jcte.2015.05.001
Downloads
Published
How to Cite
License
Copyright (c) 2021 Yanti Herawati, Umi Kalsum, I Wayan Arsana Wiyasa, Lelly Yuniarti, Teguh Wahju Sardjono (Author)
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
http://creativecommons.org/licenses/by-nc/4.0
