Effectiveness of pineapple and papaya leaf combination for dysmenorrhea pain relief in mice (Mus musculus)

Submitted: 13 October 2023
Accepted: 22 December 2023
Published: 23 February 2024
Abstract Views: 1322
PDF: 219
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Dysmenorrhea is a common gynecological condition in women, often attributed to excessive prostaglandin production, significantly impacting daily activities. Papaya leaves, known for their medicinal properties, are a chosen herbal remedy, albeit with a bitter taste, necessitating combination with pineapple fruit. This study aimed to assess the effectiveness of a combination of papaya leaf extract and pineapple fruit as an alternative treatment for primary dysmenorrhea. In an experimental research design employing the posttest-only control group, 32 male mice were divided into seven groups, injected with acetic acid as a pain inducer, and their writhing responses were recorded for 45 minutes at 15-minute intervals. Data analysis using the ANOVA test revealed significant differences in the number of writhing responses in mice (p <0.05) compared to the positive control group, followed by the Duncan test. The percentage of analgesic protection was as follows: mefenamic acid (61.01%), pineapple fruit extract (62.78%), papaya leaf extract (63.39%), a combination of pineapple and papaya leaf extracts with a dose ratio of 3:1 (73.21%), 2:2 (47.32%), and 1:3 (37.78%). In conclusion, the combination of pineapple extract and papaya leaves in a dose ratio of 3:1 demonstrated the most effective pain reduction.

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Nursalam N, Oktaviani DWDWD, Armini NKAKA, Efendi F. Analysis of the stressor and coping strategies of adolescents with dysmenorrhoea. Indian J Public Heal Res Dev 2018;9:381–6. DOI: https://doi.org/10.5958/0976-5506.2018.01373.6
Iacovides S, Avidon I, Baker FC. What we know about primary dysmenorrhea today: A critical review. Hum Reprod Update 2015;21:762–78. DOI: https://doi.org/10.1093/humupd/dmv039
Sumaryani S, Puspita Sari PI. Ar Rahman-Based Dysmenorrhea Gymnastic to Reduce Pain. J Ners 2015;10:360–5. DOI: https://doi.org/10.20473/jn.v10i2.1409
Noor S, Norfitri R. The Changes of Premenstrual Symptoms after Aerobic Exercise Intervention. J Ners 2015;10:38–47. DOI: https://doi.org/10.20473/jn.v10i1.1856
Ju H, Jones M, Mishra G. The prevalence and risk factors of dysmenorrhea. Epidemiol Rev 2014;36:104–13. DOI: https://doi.org/10.1093/epirev/mxt009
Najafi N, Khalkhali H, Moghaddam Tabrizi F, Zarrin R. Major dietary patterns in relation to menstrual pain: a nested case control study. BMC Womens Health 2018;18:69. DOI: https://doi.org/10.1186/s12905-018-0558-4
Kusumaningrum T, Nastiti AA, Dewi LC, Lutfiani A. The correlation between physical activity and primary dysmenorrhea in female adolescents. Indian J Public Heal Res Dev 2019;10:2559–63. DOI: https://doi.org/10.5958/0976-5506.2019.02252.6
Handayani SG, Ayubi N, Komaini A, et al. N-3 polyunsaturated fatty acids (PUFAs) and physical exercise have the potential to reduce pain intensity in women with primary dysmenorrhea: Systematic Review. Retos 2023;48:106–12. DOI: https://doi.org/10.47197/retos.v48.96629
Yuliani P, Estu N. Hubungan Antara Dismenorea Dengan Aktivitas Belajar Siswa Smp N 4 Boyolali. J Kebidanan 2011;20–6.
Imandiri A, Faizah R, Rakhmawati. Acupuncture and papaya leaf powder (Carica papaya L) to treat dysmenorrhea. Malaysian J Med Heal Sci 2019;15:37–9.
Ogunfowokan AA, Babatunde OA. Management of primary dysmenorrhea by school adolescents in ILE-IFE, Nigeria. J Sch Nurs 2010;26:131–6. DOI: https://doi.org/10.1177/1059840509349723
Abidah SN, Hadisaputro S, Runjati R, et al. Effect of Carica Papaya L Leaf on Menstrual Pain and Prostaglandin Level in Adolescent With Primary Dysmenorrhea: a True Experiment. Belitung Nurs J 2017;3:198–204. DOI: https://doi.org/10.33546/bnj.96
Octavianus S, Lolo WA. Uji Efek Analgetik Ekstrak Etanol Daun Pepaya (Carica Papaya L) Pada Mencit Putih Jantan (Mus Mucculus). Pharmacon 2014;3:87–92.
Sudarwati TPL, Kusumo GG, Hanny Ferry Fernanda MA, et al. Bioautography of ethanol extract from carica papaya leaves for antimicrobial activity against Staphylococcus Aureus, E. Coli and Bacillus Subtillis. Ecol Environ Conserv 2021;27:917–20.
Goel B, Maurya NK. Overview on: Herbs Use in Treatment of Primary Dysmenorrhea (Menstrual Cramps). Adv Zool Bot 2019;7:47–52. DOI: https://doi.org/10.13189/azb.2019.070302
Amran N. Efek Analgetik Kombinasi Ekstrak Buah Belimbing Wuluh (Averrhoa bilimbi L) dan Ekstrak Daun Pepaya (Carica papaya L.) pada Mencit (Mus Musculus). As-syifaa J Farm 2018;10:213–20. DOI: https://doi.org/10.33096/ja.v10i2.430
Amalia F, Abrori C, Sutejo IR, Kalimantan J. Efektivitas Analgesik Kombinasi Parasetamol dan Ekstrak Kasar Nanas terhadap Refleks Geliat Mencit yang Diinduksi Asam Asetat. 2017;5:6.
Courtney A, ed. Formularies. Pocket Handbook of Nonhuman Primate Clinical Medicine, Taylor and Francis, Boca Raton, 2012; p. 213–8. DOI: https://doi.org/10.1201/b12934-13
Yusuf H, Husna F, Gani BA, Garrido G. The chemical composition of the ethanolic extract from Chromolaena odorata leaves correlates with the cytotoxicity exhibited against colorectal and breast cancer cell lines. J Pharm Pharmacogn Res. 2021;9(3):344–56. DOI: https://doi.org/10.56499/jppres20.969_9.3.344
Gupta AK, Parasar D, Sagar A, et al. Analgesic and anti-inflammatory properties of gelsolin in acetic acid induced writhing, tail immersion and carrageenan induced paw edema in mice. PLoS One 2015;10:e0135558. DOI: https://doi.org/10.1371/journal.pone.0135558
Dawood MY. Dysmenorrhoea and prostaglandins: Pharmacological and therapeutic considerations. Curr Ther (Seaforth) 1982;23:71–83.
Barcikowska Z, Rajkowska-Labon E, Grzybowska ME, et al. Inflammatory Markers in Dysmenorrhea and Therapeutic Options. Int J Environ Res Public Health 2020;17:1191. DOI: https://doi.org/10.3390/ijerph17041191
Masruroh L, Muniroh L. The Correlation Between Nutritional Status And Calcium Adequace Level On The Incidence Of Premenstrual Syndrome (PMS) In Female Students At The Faculty Of Public Health Universitas Airlangga. Indones J Public Heal 2021;16:426–36. DOI: https://doi.org/10.20473/ijph.v16i3.2021.426-436
Armini NKA, Zahriya AN, Hidayati L, Dewi KI. Physical activity and anxiety with complaints of PMS in adolescents during the COVID-19 pandemic. Int J Public Heal Sci 2022;11:601–6. DOI: https://doi.org/10.11591/ijphs.v11i2.21242
Itani R, Soubra L, Karout S, et al. Primary Dysmenorrhea: Pathophysiology, Diagnosis, and Treatment Updates. Korean J Fam Med 2022;43:101–8. DOI: https://doi.org/10.4082/kjfm.21.0103
Wong J, Chiang YF, Shih YH, et al. Salvia sclarea l. Essential oil extract and its antioxidative phytochemical sclareol inhibit oxytocin-induced uterine hypercontraction dysmenorrhea model by inhibiting the ca2+–mlck–mlc20 signaling cascade: An ex vivo and in vivo study. Antioxidants 2020;9:1–16. DOI: https://doi.org/10.3390/antiox9100991
Kidd BL, Urban LA. Mechanisms of inflammatory pain. Br J Anaesth 2001;87:3–11. DOI: https://doi.org/10.1093/bja/87.1.3
Yam MF, Loh YC, Tan CS, et al. General pathways of pain sensation and the major neurotransmitters involved in pain regulation. Int J Mol Sci 2018;19:2164. DOI: https://doi.org/10.3390/ijms19082164
Anaga AO, Onehi E V. Antinociceptive and anti-inflammatory effects of the methanol seed extract of Carica papaya in mice and rats. African J Pharm Pharmacol 2010;4:140–4.
Ajayi AM, Coker AI, Oyebanjo OT, et al. Ananas comosus (L) Merrill (pineapple) fruit peel extract demonstrates antimalarial, anti-nociceptive and anti-inflammatory activities in experimental models. J Ethnopharmacol 2022;282:114576. DOI: https://doi.org/10.1016/j.jep.2021.114576
Wrisnijati D, Wiboworini B, Sugiarto S. Effects of Pineapple Juice and Ginger Drink for Relieving Primary Dysmenorrhea Pain among Adolescents. Indones J Med 2019;4:96–104. DOI: https://doi.org/10.26911/theijmed.2019.04.02.03
Verri WA, Vicentini FTMC, Baracat MM, et al. Flavonoids as anti-inflammatory and analgesic drugs: Mechanisms of action and perspectives in the development of pharmaceutical forms. 1st ed. Vol. 36, Studies in Natural Products Chemistry. Elsevier B.V., 2012; 297–330 p. DOI: https://doi.org/10.1016/B978-0-444-53836-9.00026-8
Ferraz CR, Carvalho TT, Manchope MF, Artero NA, Rasquel-Oliveira FS, Fattori V, et al. Therapeutic potential of flavonoids in pain and inflammation: Mechanisms of action, pre-clinical and clinical data, and pharmaceutical development. Molecules 2020;25:1–35. DOI: https://doi.org/10.3390/molecules25030762
Pavan R, Jain S, Shraddha, Kumar A. Properties and Therapeutic Application of Bromelain: A Review. Biotechnol Res Int 2012;2012:1–6. DOI: https://doi.org/10.1155/2012/976203
Brien S, Lewith G, Walker A, et al. Bromelain as a Treatment for Osteoarthritis: a Review of Clinical Studies. Evidence-Based Complement Altern Med 2004;1:251–7. DOI: https://doi.org/10.1093/ecam/neh035
Kumakura S, Yamashita M, Tsurufuji S. Effect of bromelain on kaolin-induced inflammation in rats. Eur J Pharmacol 1988;150:295–301. DOI: https://doi.org/10.1016/0014-2999(88)90010-6
Helmy SA, El-Bedaiwy HM, El-Masry SM. Effect of pineapple juice on the pharmacokinetics of celecoxib and montelukast in humans. Ther Deliv 2020;11:301–11. DOI: https://doi.org/10.4155/tde-2020-0020
Bakare AO, Owoyele BV. Bromelain reduced pro-inflammatory mediators as a common pathway that mediate antinociceptive and anti-anxiety effects in sciatic nerve ligated Wistar rats. Sci Rep 2021;11:1–13. DOI: https://doi.org/10.1038/s41598-020-79421-9
Ma H, Su S, Duan J, et al. Evaluation of the analgesic activities of the crude aqueous extract and fractions of Shao Fu Zhu Yu decoction. Pharm Biol 2011;49:137–45. DOI: https://doi.org/10.3109/13880209.2010.504965
Zendehdel M, Torabi Z, Hassanpour S. Antinociceptive mechanisms of Bunium persicum essential oil in the mouse writhing test: Role of opioidergic and histaminergic systems. Vet Med (Praha) 2015;60:63–70. DOI: https://doi.org/10.17221/7988-VETMED
Uddin MJ, Reza ASMA, Abdullah-Al-Mamun M, et al. Antinociceptive and anxiolytic and sedative effects of methanol extract of anisomeles indica: An experimental assessment in mice and computer aided models. Front Pharmacol 2018;9:1–16. DOI: https://doi.org/10.3389/fphar.2018.00246
Ribeiro RA, Vale ML, Thomazzi SM, et al. Involvement of resident macrophages and mast cells in the writhing nociceptive response induced by zymosan and acetic acid in mice. Eur J Pharmacol 2000;387:111–8. DOI: https://doi.org/10.1016/S0014-2999(99)00790-6
Gawade SP. Acetic acid induced painful endogenous infliction in writhing test on mice. J Pharmacol Pharmacother 2012;3:348. DOI: https://doi.org/10.4103/0976-500X.103699
Jahan H, Siddiqui NN, Iqbal S, et al. Suppression of COX-2/PGE2 levels by carbazole-linked triazoles via modulating methylglyoxal-AGEs and glucose-AGEs – induced ROS/NF-κB signaling in monocytes. Cell Signal 2022;97. DOI: https://doi.org/10.1016/j.cellsig.2022.110372
Aminuddin M, Sargowo D, Sardjono TW, Widjiati W. Curcuma longa supplementation reduces MDA, TNF-α, and IL-6 levels in a rat model exposed to soot particulates. Open Vet J 2023;13:11–9. DOI: https://doi.org/10.5455/OVJ.2023.v13.i1.2
Henneh IT, Armah FA, Ameyaw EO, et al. Analgesic Effect of Ziziphus abyssinica Involves Inhibition of Inflammatory Mediators and Modulation of KATP Channels, Opioidergic and Nitrergic Pathways. Front Pharmacol 2021;12:1–15. DOI: https://doi.org/10.3389/fphar.2021.714722

How to Cite

Syam, H., Masitoh, S., Safira Purwanto, U. M., Muzakkiyah, H., Fadhila, R., & Mulyani, S. (2024). Effectiveness of pineapple and papaya leaf combination for dysmenorrhea pain relief in mice (<i>Mus musculus</i>). Healthcare in Low-Resource Settings, 12(3). https://doi.org/10.4081/hls.2024.11968