Asian Pacific Journal of Tropical Biomedicine (2011)330-333

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Asian Pacific Journal of Tropical Biomedicine
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Dengue fever treatment with Carica papaya leaves extracts
Nisar Ahmad1, 2 , Hina Fazal 1, 3, Muhammad Ayaz4, Bilal Haider Abbasi1, Ijaz Mohammad5, Lubna Fazal5
Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad 45320, Pakistan Nuclear Institute for Food and Agriculture (NIFA) Tarnab, Peshawar 25000, Pakistan 3 Pakistan Council of Scientific and Industrial Research (PCSIR) Laboratories Complex, Peshawar 25000, Pakistan 4 Department of Environmental Sciences, University of Peshawar, Peshawar 25000, Pakistan 5 Postgraduate Medical Institute (PGMI), Lady Reading Hospital, Peshawar 25000, Pakistan
1 2


Article history: Received 28 February 2011 Received in revised form 20 March Accepted 6 April 2011 Available online 30 April 2011 Keywords: Dengue fever

The main objective of the current study is to investigate the potential of Carica papaya leaves extracts against Dengue fever in 45 year old patient bitten by carrier mosquitoes. For the treatment of Dengue fever the extract was prepared in water. 25 mL of aqueous extract of C. papaya leaves was administered to patient infected with Dengue fever twice daily i.e. morning and evening for five consecutive days. Before the extract administration the blood samples from patient were analyzed. Platelets count (PLT), White Blood Cells (WBC) and Neutrophils (NEUT) decreased from 176暳103/毺L, 8.10暳103/毺L, 84.0% to 55暳103/毺L, 3.7暳103/毺L and 46.0%. Subsequently, the blood samples were rechecked after the administration of leaves extract. It was observed that the PLT count increased from 55暳103/毺L to 168暳103/毺L, WBC from 3.7暳103/毺L to 7.7暳103/毺L and NEUT from 46.0% to 78.3%. From the patient feelings and blood reports it showed that Carica papaya leaves aqueous extract exhibited potential activity against Dengue fever. Furthermore, the different parts of this valuable specie can be further used as a strong natural candidate against viral diseases.


Leaves extracts Platelets Potential activity

Carica papaya

1. Introduction
D engue viruses, mosquito-borne members of the Flaviviridae family, are the causative agents of dengue fever [1]. D engue is the most important emerging viral

disease of humans that in recent decades has become a major international public health concern. Dengue is found in tropical and sub-tropical regions around the world, predominantly in urban and semi-urban area [2]. It is estimated that there are between 50 and 100 million cases of dengue fever ( DF ) and about 500 000 cases of dengue haemorrhagic fever (DHF) each year which require hospitalization [3]. D engue fever is spread through the bite of an infected Aedes aegypti mosquito. The mosquito gets the virus by biting an infected person [4]. The first symptom of the disease appears in about 5-7 days after the infected mosquito bites a healthy person. It is possible to become infected by dengue multiple times because the virus has four different serotypes. A lthough each infection confers lifelong immunity to that particular

*Corresponding author: Nisar Ahmad, PhD student, Department of Biotechnology, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad-45320, Pakistan. Tel: +92-332-9959234 E-mail: nisarbiotech@gmail.com

serotype, a subsequent infection with a different serotype increases the risk of contracting the much deadlier form known as dengue hemorrhagic fever (DHF)[5]. The symptoms of dengue fever include high fever, rash, and a severe headache (dengue triad). Additional symptoms include severe joint and muscular pain (breakbone fever), nausea, vomiting, and eye pain. Although dengue fever itself is rarely fatal, it can be an extraordinarily painful and disabling illness and may become epidemic in a population following the introduction of a new serotype. Dengue fever is usually a self-limited illness, and only supportive care is required. Acetaminophen may be used to treat patients with symptomatic fever. Aspirin, Brufen nonsteroidal anti-inflammatory drugs (NSAIDs), antibiotics and corticosteroids should be avoided as these do not help but cause gastritis and/or bleeding. In children, Reye’s syndrome (encephalopathy) may be a serious complication. Patients with known or suspected dengue fever should have their platelet count and Hematocrit measured daily from the third day of illness until 1-2 days after defervescence. N o vaccine is available for the prevention of dengue infection. Immunogenic, safe tetravalent vaccines have been developed and are undergoing clinical trials. The only way to prevent dengue virus acquisition is to avoid being bitten by a vector mosquito[1-4]. Fresh plant materials of

these symptoms aggravated over the night. 4. respectively. red skin.1 Ps 3 6 3 5th day s/dL 3 176暳10 /毺L 10.7% 81.7 fL 33. But in this case on the fourth and fifth day the PLT count decreased to 71暳103/毺L and 55暳103/毺L.1 55暳10 /毺L 17% 46% 32.from the tests results it was observed that PLT.3 s/dL 3 71暳10 /毺L - 34. White Blood Cells (WBC). Different antibiotics and anti-malarial drugs were administrated orally and intravenously.e.5 86. Lajber Khan. sever body pain and high blood pressure. About 25 mL of leaves extract was administrated orally. respectively. the leaves of the plant (Figure 2) were collected and thoroughly washed with water. 3 3. These symptoms increased time to time over the passing hours. WBC and NEUT decreased from normal level.94暳10 /毺L 14. the patient blood test have been taken. WBC 6.7 fL 43. From the first blood report it was observed that 3 PLT count was176暳103/毺L. Before extract administration.6 27.0 fL 42.00暳10 /毺L 15.4 fL 31.60暳10 /毺L 3 6 2nd day 3rd day 6 s/dL 4. As the taste of C.7暳10 /毺L and 60.9暳10 /毺L 3 0. 25 mL of aqueous extract of C.6暳10 /毺L and NEUT 81.2 fL 20. and his condition became Parameters WBC RBC HGB HCT MCV MCH MCHC PLT LYM% MXD% NEUT% LYM # MXD # NEUT # RDW PDW P-LCR MPV 1st Table 1 Blood test reports before the administration of C. The plant material was washed with water. After which the patient starts improvement. Pakistan.5% 7. During his journey he used to stay at different locations for food. Pakistan.7% 71. PLT. papaya) were collected from University of Peshawar. after 24 hours each time.3 fL 31.5% 3 0.Nisar Ahmad et al.4 86. some amount of sucrose was added for easy administration. etc.2 Ps 90 fL 42% s/dL 3 110暳10 /毺L 20.96暳10 /毺L 13.3暳10 /毺L 3 3. papaya leaves extract. In the same days three to four patients surrounding the mentioned area (Figure 1) died of Dengue fever. By 72 hours.5 fL 15.2s/dL 27. 46. In the second report PLT count was 122暳 3 3 10 /毺L. Therefore.10暳10 /毺L 5.9 Ps 87. The separated serum profile was used for the estimation of biochemical parameters like Platelets count (PLT). PCSIR Laboratories Complex.2% 9.6% 3 6 worse time by time. B efore administration of leaves extracts. Serum was separated by centrifugation at 3 000 rpm for 15 minutes. which were followed by vomiting.3s/dL 28. Case report A male patient aged 45 years old working as truck driver in a cement factory. twice daily for five consecutive days.8% 4. morning and evening for five consecutive days.7 fL 8. 4. so from the patient symptoms and blood reports physicians recommended hospitalization.9% 4. 2.4 fL 45.00暳10 /毺L 5. After extract administration the patient blood was rechecked for platelets counts again for five consecutive days. the patient blood was evaluated for total platelets counts.4暳10 /毺L 3 331 day 6.3% 84. WBC and NEUT decreased very fast.1暳10 /毺L and NEUT 84.9 fL 14.9暳10 /毺L 3 0. The serological studies revealed an abrupt decline in the patient platelets counts.23暳10 /毺L 16. After the infection the patient immediately felt fatigue and fever. Head. but no successful results.1 Ps 36% 60% 90 fL 47% 6 3 4th day 3. After 24 hr of which he started feeling sever pain in whole body with fever and teary eyes. The third day report showed the PLT counts. In the same month of October 2010. while the WBC and NEUT reached to 4. On the basis of screening blood test examination he was declared to be a victim of Dengue fever. most patients of Dengue fever died.5%. shivering.0%.WBC 8.8%.8暳10 /毺L 43. The physicians told the family members of patient that if the PLT count were below 20暳103/ 毺L then he would begin bleeding and may die. cut into pieces and grinded with blender.5 fL 11.0% 3 0.28暳10 /毺L 14. The symptom included breathing problem.1 s/dL - - - .0% respectively (Table 1). Red Blood Cells (RBC) and Neutrophils (NEUT). At the same time our team was working on the biological activities of C. papaya. sever vomiting.9暳10 /毺L 3 0.4暳10 /毺L 44. Medicinal Botanic Centre (MBC). The leaves were grinded in fruit juicer with water. at that time he was bitten by mosquito carrying Dengue virus. 8. WBC and NEUT were 110暳 3 3 10 /毺L.4 27.3 Ps s/dL 3 122暳10 /毺L 13.8% 3 0. effectiveness of the water extract was investigated biochemically from blood samples.4 fL 9. papaya leaves was administered to patient infected with Dengue fever.0暳103/毺L.4暳10 /毺L and 71. For the patient’s treatment. The patient has been given different broad spectrum antibiotics and anti malarial drugs but there were no signs of improvement. respectively. The same doze was given to the patient twice daily i. Their botanical identities were determined and authenticated by Dr.7% 5. In patient target area there was no specific lab to identify Dengue virus in patient blood.2s/dL 31.0% s/dL 4. Subsequently the patient was admitted in emergency unit in Abottabad Medical Complex. Physicians in different hospital recommend PLTs injection isolated from donor blood./Asian Pacific Journal of Tropical Biomedicine (2011)330-333 Carica papaya (C. He had been given different food items but unfortunately vomiting did not stopped.1% 8. papaya leaves extract was very bitter. He reported that he had been driving truck and transporting cement to various regions of KPK.0%.70暳10 /毺L 5. Peshawar KPK.2暳10 /毺L 48.3暳10 /毺L 3 5. was brought to the emergency department with sever fever of 104 曘F.4暳10 /毺L 3 6.

5 86.1% 3 3 3 34.2 Ps s/dL 5.40暳10 /毺L 3 2nd day 6 5.4 fL 6.6 fL 7.80暳10 /毺L 45.5 32.1%) increased.5 Ps s/dL 137暳10 /毺L 20. Fagonia indica.70暳10 /毺L 5. WBC: 7.6 Ps 40% s/dL 120暳10 /毺L 42. Sterculia guttata. respectively.9暳10 /毺L and NEUT: 73..30暳10 /毺L 4.2 89.5% 71. .3% 35.0 fL 3 4.90暳10 /毺L 5. With similar dose of extracts.0% 3 3 3 36.71暳10 /毺L 15.80暳10 /毺L - 73.2%. D ifferent age leaves of C.1 Ps 31% s/dL 168暳10 /毺L 19% 78. Many plants extracts including Spilanthes calva.8 31. Artemisia annua. WBC and NEUT reach to their normal levels (Table 2).6% 0.8暳10 /毺L and 56./Asian Pacific Journal of Tropical Biomedicine (2011)330-333 Table 2 Blood test reports after the administration of C.1% s/dL 5.0 fL 3 3 6 3rd day 5.80暳10 /毺L 3 1st day 6 42.6% s/dL 73暳10 /毺L 56.99暳10 /毺L 14. it was observed that PLT count (137暳103/毺L).24暳10 /毺L 0. After two consecutive days the blood samples were checked for different parameters.33暳10 /毺L 16. Parameters WBC RBC HGB HCT MCV MCH MCHC PLT LYM% MXD% NEUT% LYM # MXD # NEUT # RDW PDW P-LCR MPV 4.3%) the PLT. Figure 1. Trigonella foenum.26暳10 /毺L 15. Solanum xanthocarpum.0% 64.5 fL 19.9 fL 11.20暳10 /毺L 43. Figure 2. 3.2 fL 8. WBC (5.7暳103/毺L and NEUT: 78.4% 6. WBC: 5.6 fL 3 3 6 5th day 48. 25 mL of extract was given to the patient in the morning and evening. Vitex negundo. In the first blood report it was observed that the PLT count. 3.2% 3 3 3 34. Balanites aegyptiaca.3暳103/毺 L) and NEUT (71.4暳103/毺L and 64. Nerium indicum.27暳10 /毺L 0.2% 0.1 27.0%.2% s/dL 42. T here have been many reports of higher plant extracts possessing relatively good potential to inhibit viruses (Van Den Berghe.31暳10 /毺L 3. Discussion The main objective of the current study is to investigate the potential of C. so physicians recommended fruits and fruit juices.0 84.1 fL 0.0% - - - The C. The target area of Dengue fever.7 fL 14. a vector of dengue fever[6-12]. papaya used for aqueous extraction.8 90.20暳10 /毺L 46. WBC and NEUT increased to 73 3 3 暳10 /毺L.7 fL 3. The patient started vomiting as eating.2 86.70暳10 /毺L 5. papaya leaves extracts against Dengue fever.3 28.9 Ps s/dL 159暳10 /毺L 34.332 Nisar Ahmad et al. papaya leaves extract. on the next day the blood report indicated that the PLT count reach to120暳103/毺L while WBC and NEUT reach to 4. papaya leaves extract in water was given to the patient twice daily. 1978).0 fL 3 3.9% s/dL 46% s/dL 46.3% 4.90暳10 /毺L 6. On the third day. The secondary metabolite of plants origin makes up a vast repository of compounds with a wide range of biological activities. in different solvents have been reported to exhibit activity against Aedes aegypti L.6 fL 3 3 6 4th day 7. In the fourth blood report (PLT: 3 3 159暳10 /毺L. respectively.7% 0.21暳10 /毺L 16.1 fL 13.0%) and fifth 3 report (PLT: 168暳10 /毺L.1 29.

2: 72-76. a hydrolase. Effectiveness of dried Carica papaya seeds against human intestinal parasitosis: A pilot study. Hafeez F. Muliawanb HS. root. 42: 3343-3348. Parasitol Res 2007. Carica papaya lipase (CPL): An emerging and versatile biocatalyst. [15] Okeniyi JA. cypermethrin. which is tightly bonded to the water-insoluble fraction of crude papain and is thus considered as a “naturally immobilized” biocatalyst[14]. [2] Akram W. It is reported that the plant extracts of Quercus lusitanica have maximum activity against DENV-2 Replication of Dengue virus[17]. 26: 657-660. papaya contains two important biologically active compounds vis: chymopapain and papain which are widely used for digestive disorders[13]. significantly reduced replication of dengue virus serotype 2 (DENV-2) in cultured Vero cells and a noval trypsin Kazal-type inhibitor from Aedes aegypti has thrombin coagulant inhibitory activity[20]. J Med Food 2007. Gonzales SR. [17] Rahmana NA. [9] Mohan L. Jeselnik M. strongly interferes with Dengue 2 virus infection in vitro. It showed that papayaderived papain. Hebbalkar GD. Larvicidal activity of Leucas asper (Willd) against the larvae of Culex quinquefasciatus Say. [5] Morens. chymopapain. Patel JA. Bartik K. Hayden M. Khan HAA. Unripe and semi. Srivastava SS. Seeds and fruits are excellent antihelminthic and antiamoebic[15]. Geneva: WHO.). Biochem Biophys Res Commun 2006. Kim YK. [19] McDowell M. papaya are lipase. Tungikar VB. Wintjens R. Anopheles culicifacies. It is also reported that the methyle gallate of plant origin interacts with herpes simplex virus proteins and alters the adsorption and penetration of the virion[18]. Strong larvicidal activity of three species of Spilanthes (Akarkara) against malaria (Anopheles stephensi Liston.2. Pawar PV. Agrawal V. or CPL. et al. Fauci. also the leaf decoction is administered as a purgative for horses and used for the treatment of genito-urinary system. papaya leaves extract. Dengue Bull 2006. The rise of PLT count in the present case from 55暳103/毺L to 168暳103/毺L indicates the activity of C. and glycine endopeptidase can improve acidic p H conditions and pepsin degradation. [7] Katade SR. medicinal and pharmacological properties of papaya (Carica papaya Linn. Most patients infected are in the age of 30-45 years old. WSS45. Muhamadb M. However. Raghavendra K. Anopheles stephensi. Bilal H.4]triazole (ETAR) and 1-beta-Dribofuranosyl4 -ethynyl[ 1 . Hanley KA. but consumption of ripe fruits during pregnancy causes no risk[16]. papaya leaves extracts against Dengue fever./Asian Pacific Journal of Tropical Biomedicine (2011)330-333 C. Pak J Bot 2010. 87: 78-80. Tanaka-Azevedo AM. Shi LP. Bhatnagar VP. Qiu H. seeds juice. Maciel C. 44: 662-665. 77: 420-424. Paridhavi M. Inter J Integrative Biol 2008. Review on nutritional. J Biopest 2009. A novel trypsin kazal-type inhibitor from Aedes aegypti with thrombin coagulant inhibitory activity. Capurro ML. hepatoprotective. Other active compounds of C. immunomodulatory and against histminergic[21]. antimalarial. T sai SW . [14] D ominguez de M aria P . Conflict of interest statement We declare that we have no conflict of interest. A lcantara AR. Bartarya R. and Aedes aegypti L. A web-based multimedia spatial information system to document Aedes aegypti breeding sites and dengue fever risk along the US-Mexico border. Southeast Asian J Trop Med & Public Health 2007. papaya are used as antimicrobial. anthelmentic. 2. species C) and filaria vector (Culex quinquefasciatus Say). a sulfated alpha-D-glucan. Sterculia guttata seeds extractives an effective mosquito larvicide. [16] Adebowale A. Wang GF. Rashidb NN. Effective method for extraction of larvicidal component from leaves of Azadirachta indica and Artemisia annua Linn. 3 ]imidazole ( IM 18 ) . Deshpande VH. It is observed that Gastrodia elata B1 has effect on the multiplication cycle of Dengue virus serotype 2[19]. Nat Prod Radiance 2008. Pawar PV. [8] Wiesman Z. [20] Watanabe RM. et al. 2: 214-217. the consumption of unripe and semi-ripe papaya fruits could be unsafe during pregnancy.ripe papaya fruits are ingested or applied on the uterus to cause abortion. 31: 585-592. 92: 933-939. Dash AP. 24: 493-499. Looze Y. antifungal. Ji FH. References [1] Murthy JM. Wakharkar RD. Ind J Exp Biol 2006. J Environ Biol 2005. Soares TS. leaves. It is reported that two compounds 1-beta-D-ribofuranosyl-3ethynyl-[1. 38: 256-260. Acta Pharmacol Sin 2010. British J Nutr 2002. Papaya (Carica papaya) consumption is unsafe in pregnancy: Fact or fable? Scientific evaluation of a common belief in some parts of Asia using a rat model. However. 341: 620-626. [11] Chaubal R. unripe fruits. Aedes albopic Tus (Skuse) (Culicidaea). The Dengue attacks start in late summer and end in early winter in Pakistan. Ogunlesi TA. Mosquito thrives. [21] Karishna KL. 333 . The Dengue fever repeats every year and causes several deaths. [3] Maheswaran R. exhibits efficacy against a broad range of flaviviruses in vitro. Chapagain. seeds. et al. Biological activity of certain botanical extracts as larvicides against the yellow fever mosquito. Dried and pulverized leaves are sold for making tea. ripe fruits. 88: 199-203. Larvicidal activity of Acacia nilotica extracts and isolation of D-pinitol-a bioactive carbohydrate. Brody JE. [13] Huet J. Boussard P. The latex. against malaria vector. Potential of citrus seed extracts against Dengue fever mosquito. Antiviral Res 2010. M ohan L . Fitoterapia 2006. Ignacimathu S. Morais-Zani K. Studies on Quercus lusitanica extracts on DENV-2 replication. so does dengue fever. Deshpande NR. 12: 715-727. Rani PU. Puranik VG. 102: 171-174. S inisterra JV . Yusofb R. 2: 684-688. Raussens V. Comparative efficacy of Solanum xanthocarpum extracts alone and in combination with a synthetic pyrethroid. [4] Moreno-Sanchez R. Satish S. According to the folk medicine. papaya latex can cure dyspepsia and also applicable for external burns and scalds. Zhang X. Health & Place 2006. Lee JJ. Structural characterization of the papaya cysteine proteinases at low pH.Nisar Ahmad et al. L arvicidal potential of Nerium indicum and Thuja oriertelis extracts against malaria and Japanese encephalitis vector. [6] Pandey V. 1-beta-Dribofuranosyl-3-ethyl-[1. Biochimie 2010. Prasad RNV. 27: 103-105. Larvicidal activity of saponin containing extracts and fractions of fruit mesocarp of Balanites aegyptiac. A novel nucleoside analog. Bishnu P. antiamoebic. Garnesan AP. this is a preliminary work and more works on isolating the active compounds from this valuable specie are needed which may help in control of such infectious diseases. S rivastava CN . 10: 194-196. Srivastava CN. [18] Tong XK. Chemi Biodivers 2005. Janes C. Kumarapperama SC. [10] Tonk S. Oyelami OA. 7: 364-373. Maharaj KK. 2008. 4] triazole (ETAR). 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