The Papaya-Based Poly-Herbal Extract Eases Thrombocytopenia and Pyrexia in Rats
Abstract
The beneficial role of papaya leaf juice against dengue infection is gaining popularity. However, most of these studies involve the fresh juice, decoction, or solvent extraction methods with limitations in terms of formulation development and retention of natural phytochemical balance. Hence, this study aimed at investigating the platelet-increasing and anti-pyretic effect of its powdered extracts with favorable attributes for developing finished pharmaceuticals. The former activity was performed on papaya leaves powder extract (PE) used to prepare the product, i.e., Re-Plat. However, both activities were assessed on the multi-ingredients extract (ME; composition was PE plus decoction of Achillea millefolium, Zingiber officinale, Phyllanthus niruri and Piper nigrum) used in the poly herbal formulation i.e. Re-Plat Plus. Briefly, the Carboplatin (50 mg/kg) was used to develop a rat model of thrombocytopenia, which is followed by the administration of PE and ME (150, 300, and 450 mg/kg). After five days, the blood was collected to measure platelet levels using a hematology analyzer. In case of anti-pyretic activity, the yeast-induced pyrexia model was used to induce pyrexia followed by administration of ME (150, 300, and 450 mg/kg). The rectal temperature was noted for 5 h. Our data showed that, at the tested doses of 150 and 300 mg/kg, both PE and ME caused significant increase in the platelet count compared to the control group. In case of anti-pyretic activity, in similarity with standard drug (paracetamol), the PE (300 and 450 mg/kg) did not allow time-dependent increase in the temperature. Hence, it can be deduced that the active extracts of the poly-herbal formulation (Re-Plat Plus) are endowed with the platelet increase and anti-pyretic potentials; the attributed clinically useful in the management of dengue fever.
Keywords: papaya, dengue, platelets, pyrexia, thrombocytopenia.
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ROY S. K., & BHATTACHARJEE S. Dengue virus: epidemiology, biology, and disease aetiology. Canadian Journal of Microbiology, 2021, 67(10): 687-702. https://doi.org/10.1139/cjm-2020-0572
SHEPARD D. S., UNDURRAGA E. A., HALASA Y. A., and STANAWAY J. D. The global economic burden of dengue: a systematic analysis. The Lancet Infectious Diseases, 2016, 16(8): 935-941. https://doi.org/10.1016/s1473-3099(16)00146-8
BHATT S., GETHING P. W., BRADY O. J., MESSINA J. P., FARLOW A. W., MOYES C. L., DRAKE J. M., BROWNSTEIN J. S., HOEN A. G., SANKOH O., MYERS M. F., GEORGE D. B., JAENISCH T., WINT G. R., SIMMONS C. P., SCOTT T. W., FARRAR J. J., and HAY S. I. The global distribution and burden of dengue. Nature, 2013, 496(7446): 504-507. https://doi.org/10.1038/nature12060
BRADY O. J., GETHING P. W., BHATT S., MESSINA J. P., BROWNSTEIN J. S., HOEN A. G., MOYES C. L., FARLOW A. W., SCOTT T. W., and HAY S. I. Refining the global spatial limits of dengue virus transmission by evidence-based consensus. PLoS Neglected Tropical Diseases, 2012, 6(8): e1760. https://doi.org/10.1371/journal.pntd.0001760
MESSINA J. P., BRADY O. J., GOLDING N., KRAEMER M. U. G., WINT G. R. W., RAY S. E., PIGOTT D. M., SHEARER F. M., JOHNSON K., EARL L., MARCZAK L. B., SHIRUDE S., DAVIS WEAVER N., GILBERT M., VELAYUDHAN R., JONES P., JAENISCH T., SCOTT T. W., REINER JR. R. C., and HAY S. I. The current and future global distribution and population at risk of dengue. Nature Microbiology, 2019, 4(9): 1508-1515. https://doi.org/10.1038/s41564-019-0476-8
KHATRI G., HASAN M. M., SHAIKH S., MIR S. L., SAHITO A. M., PRIYA, ROCHA I. C. N., and ELMAHI O. K. O. The simultaneous crises of dengue and COVID-19 in Pakistan: a double hazard for the country’s debilitated healthcare system. Tropical Medicine, 2022, 50(1): 18. https://doi.org/10.1186/s41182-022-00410-x
KHAN U., & AZEEM S. The rising toll of dengue cases in Pakistan every year: An incipient crisis. Annals of Medicine & Surgery, 2022, 76: 103549. https://doi.org/10.1016%2Fj.amsu.2022.103549
WAHALA W. M., & DE SILVA A. M. The human antibody response to dengue virus infection. Viruses, 2011, 3(12): 2374-2395. https://doi.org/10.3390/v3122374
BALSITIS S. J., WILLIAMS K. L., LACHICA R., FLORES D., KYLE J. L., MEHLHOP E., JOHNSON S., DIAMOND M. S., BEATTY P. R., and HARRIS E. Lethal antibody enhancement of dengue disease in mice is prevented by Fc modification. PLoS Pathogens, 2010, 6(2): e1000790. https://doi.org/10.1371/journal.ppat.1000790
TORRES-FLORES J. M., REYES-SANDOVAL A., and SALAZAR M. I. Dengue Vaccines: An Update. BioDrugs, 2022, 36(3): 325-336. https://doi.org/10.1007/s40259-022-00531-z
KALA C. P. Leaf Juice of Carica papaya L.: A Remedy of Dengue Fever. Medicinal & Aromatic Plants, 2012, 1(6): 1000109. https://doi.org/10.4172/2167-0412.1000109
TEH B. P., AHMAD N. B., MOHAMAD S. B., TAN T. Y. C., MOHD ABD RAZAK M. R. B., AFZAN A. B., and SYED MOHAMED A. F. B. Carica papaya Leaf Juice for Dengue: A Scoping Review. Nutrients, 2022, 14(8): 1584. https://doi.org/10.3390/nu14081584
LIM X. Y., CHAN J. S. W., JAPRI N., LEE J. C., and TAN T. Y. C. Carica papaya L. Leaf: a systematic scoping review on biological safety and herb-drug interactions. Evidence-Based Complementary & Alternative Medicine, 2021, 2021: 511221. https://doi.org/10.1155/2021/5511221
TAGUCHI K., & ASANO M. Effect of YM294, Recombinant Human lnterleukin-11, on Carboplatin-lnduced Thrombocytopenia in Rats. Journal of Pharmaceutical Sciences, 1995, 84(12): 1442-1445. https://doi.org/10.1002/jps.2600841211
XIE F., XU L., ZHU H., CHEN Y., LI Y., NONG L., ZENG Y., and CEN S. The Potential Antipyretic Mechanism of Ellagic Acid with Brain Metabolomics Using Rats with Yeast-Induced Fever. Molecules, 2022, 27(8): 2465. https://doi.org/10.3390/molecules27082465
ULICH T. R., DEL CASTILLO J., YIN S., SWIFT S., PADILLA D., SENALDI G., BENNETT L., SHUTTER J., BOGENBERGER J., and SUN D. Megakaryocyte growth and development factor ameliorates carboplatin-induced thrombocytopenia in mice. Blood, 1995, 86(3): 971-976. https://doi.org/10.1182/blood.V86.3.971.971
AFZAN A., ABDULLAH N. R., HALIM S. Z., RASHID B. A., SEMAIL R. H., ABDULLAH N., JANTAN I., MUHAMMAD H., and ISMAIL Z. Repeated Dose 28-Days Oral Toxicity Study of Carica papaya L. Leaf Extract in Sprague Dawley Rats. Molecules, 2012, 17(4): 4326-4342. https://doi.org/10.3390/molecules17044326
DHARMARATHNA S. L., WICKRAMASINGHE S., WADUGE R. N., RAJAPAKSE R. P., and KULARATNE S. A. Does Carica papaya leaf-extract increase the platelet count? An experimental study in a murine model. Asian Pacific Journal of Tropical Biomedicine, 2013, 3(9): 720-724. https://doi.org/10.1016/s2221-1691(13)60145-8
HALIM S. Z., ABDULLAH N. R., AFZAN A., ABDUL RASHID B. A., JANTAN I., and ISMAIL Z. Acute toxicity study of Carica papaya leaf extract in Sprague Dawley rats. Journal of Medicinal Plants Research, 2011, 5: 1867-1872. https://doi.org/10.5897/JMPR.9000043
SRIKRISHNA H. A., DAS J. K. L., HANS P., HAQUE I., HIREMATH M., KUMAR G., KUMAR A., SINGH A., PUII Z., ANAND R., and BULUSU A. Clinical Evaluation for the Thrombopoietic Activity of Platenza Tablet in Cases of Dengue with Thrombocytopenia - Randomized Open Label Comparative Clinical Study. Annals of Medical & Health Sciences Research, 2018, 8: 29-38. https://www.amhsr.org/articles/clinical-evaluation-for-the-thrombopoietic-activity-of-platenza-tablet-in-cases-of-dengue-with-thrombocytopenia-randomized-open-la-4472.html
SIDDIQUE O., SUNDUS A., and IBRAHIM M. F. Effects of papaya leaves on thrombocyte counts in dengue - a case report. Journal of Pakistan Medical Association, 2014, 64(3): 364-366. https://jpma.org.pk/article-details/6137
BHATT R., PATEL K., PATEL K., PATEL K., SAURABH S., and THAKKAR D. Beneficial impact of carica papaya mother tincture in increasing thrombocyte counts in cases of dengue. International Journal of Homeopathic Sciences 2022, 6(1): 12-14. https://doi.org/10.33545/26164485.2022.v6.i1a.509
SUBENTHIRAN S., CHOON T. C., CHEONG K. C., THAYAN R., TECK M. B., MUNIANDY P. K., AFZAN A., ABDULLAH N. R., and ISMAIL Z. Carica papaya leaves juice significantly accelerates the rate of increase in platelet count among patients with dengue fever and dengue haemorrhagic fever. Evidence-Based Complementary and Alternative Medicine, 2013, 2013: 616737. https://doi.org/10.1155/2013/616737
SHARMA N., MISHRA K. P., CHANDA S., BHARDWAJ V., TANWAR H., GANJU L., KUMAR B., and SINGH S. B. Evaluation of anti-dengue activity of Carica papaya aqueous leaf extract and its role in platelet augmentation. Archives of Virology, 2019, 164(4): 1095-1110. https://doi.org/10.1007/s00705-019-04179-z
MADUSHANKA A., VERMA N., FREINDORF M., and KRAKA E. Papaya Leaf Extracts as Potential Dengue Treatment: An In-Silico Study. International Journal of Molecular Sciences, 2022, 23(20): 12310. https://doi.org/10.3390/ijms232012310
PATIL P., ALAGARASU K., CHOWDHURY D., KAKADE M., CHERIAN S., KAUSHIK S., YADAV J. P., KAUSHIK S., and PARASHAR D. In-vitro antiviral activity of Carica papaya formulations against dengue virus type 2 and chikungunya virus. Heliyon, 2022, 8(12): e11879. https://doi.org/10.1016/j.heliyon.2022.e11879
CALABRESE E. J., & AGATHOKLEOUS E. Hormesis: Transforming disciplines that rely on the dose response. IUBMB Life, 2022, 74(1): 8-23. https://doi.org/10.1002/iub.2529
AMER M., & EL-ASHRY E. S. Anti-Inflammatory, Analgesic and Antipyretic Activities of Ginger (Zingiber Officinale). Proceedings of the 8th International Scientific Conference, Mansoura, 2014, pp. 471-483. https://journals.indexcopernicus.com/api/file/viewByFileId/1034674.pdf
ALI S. I., GOPALAKRISHNAN B., and VENKATESALU V. Pharmacognosy, phytochemistry and pharmacological properties of Achillea millefolium L.: a review. Phytotherapy Research, 2017, 31(8): 1140-1161. https://doi.org/10.1002/ptr.5840
PAITHANKAR V. V., RAUT K. S., CHARDE R. M., and VYAS J. V. Phyllanthus niruri: A magic herb. Research in Pharmacy, 2015, 1(4): 1-9. https://updatepublishing.com/journal/index.php/rip/article/view/215
EMON N. U., ALAM S., RUDRA S., RIYA S. R., PAUL A., HOSSEN S. M. M., KULSUM U., and GANGULY A. Antidepressant, anxiolytic, antipyretic, and thrombolytic profiling of methanol extract of the aerial part of Piper nigrum: In vivo, in vitro, and in silico approaches. Food Science & Nutrition, 2021, 9(2): 833-846. https://doi.org/10.1002/fsn3.2047
CANINI A., ALESIANI D., D’ARCANGELO G., and TAGLIATESTA P. Gas chromatography–mass spectrometry analysis of phenolic compounds from Carica papaya L. leaf. Journal of Food Composition and Analysis, 2007, 20(7): 584-590. https://doi.org/10.1016/j.jfca.2007.03.009
AYOOLA P., & ADEYEYE A. Phytochemical and nutrient evaluation of carica papaya (pawpaw) leaves. International Journal of Research & Reviews in Applied Sciences, 2010, 5(3): 325-328. https://arpapress.com/Volumes/Vol5Issue3/IJRRAS_5_3_15.pdf
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