Phytopharmaceutical Evaluation of Various Extracts of Carica Papaya L. Against Dengue Fever

Abstract

Dengue is one of the most leading mosquito-borne viral infection, considered as one of the major health problem associated with high rate of morbidity and motility. The root cause of dengue infection are four distinct but serotypically related virus (DENV-1, 2, 3 and 4). WHO estimated about more than 50,000,000 dengue cases reported worldwide. Primarily, dengue leads to dengue fever (DF), an acute febrile illness, while Dengue Hemorrhagic Fever (DHF) or Dengue Shock Syndrome (DSS) are secondary infection to DF. To-date, there is no proper medical treatment available against dengue. Recent studies indicated a direct infection of the platelets by the dengue virus. Clinical severity associated with dengue is potentially due to thrombocytopenia while in DHF, thrombocytopenia is associated with increased vascular permeability, haemorrhagic manifestations and any further decrease in platelet counts leads to lethality. So, there is a need of a regimen that can not only improve the disease outcome but also linked with the least side effects. Investigations on the effects of fresh aqueous leaf extract of Carica papaya Linn on the thrombocytes count of DF, DHF and DSS patients has provided promising results because of the presence of alkaloids, saponins and other phenolic compounds in leaves. The use of the papaya aqueous leaf extracts is one of the most inexpensive, therapeutically effective herbal management particularly in the less privileged and dengue endemic under developing countries. The purpose of the present study was to establish the quality standard of male and female papaya leaves separately along with quantification of bioactive compounds as they are important in dengue fever management. A significant difference was observed among alkaloids, phenols and saponins in both the leaves (p<0.01). Phytoconstituents including alkaloids, phenolics and saponins were found to be significantly different (p<0.01) in both male and female aqueous and ethanolic leaf extracts. The results delineated that aqueous extracts from female plant is richer in alkaloids while male leaves are richer in phenols. Furthermore, the aqueous crude extract of both male and female plant was accessed for tablet formulation. Extracts were first accessed for microbial contamination test and were found to be negative. Pre formulation studies were performed on both male and female aqueous extracts as well as for excipients. Significant difference (p<0.01)was observed for male and female leaf extract powders relating to bulk density, tapped density and Hausner’s ratio while no significant difference is seen for angle of repose and carr’s index. FTIR analysis was done for male and female aqueous extracts and also for excipient’s compatibility. The Interferogram delineated no significant difference after the addition of excipient to both the dried aqueous extract. All the ingredient showed good flow properties so direct compression method of tablets was selected. Post formulation studies were done on the prepared aqueous male and female leaf extracts tablets including general appearance, weight variation, hardness testing, friability testing, disintegration and dissolution profiles. Significant difference (p<0.05) was observed for only in disintegration. Tablets were also tested for their stability during storage period of one month. Tablets stored at 40°C and 75% humidity failed to pass the test while at 25°C; normal humidity and 5°C; 0% humidity passed the test. Finally, both kinds of tablets were preliminary analyzed to evaluate their potential role. For the said, six dengue positive subjects (of both gender) were selected based on criteria and administered with the tablets along with the standard therapy. Their platelet count for the next five days were analyzed. Results showed significant potential of aqueous female leaf extracts tablets (p<0.05) as compared to aqueous male leaf extracts tablets in terms of increasing and stabilizing the platelet count during treatment. Previous literature reported in general that Carica papaya aqueous leaf extract can be used as a first aid oral treatment in dengue but the data did not report the difference in phytoconstituents of male and female leaves of the plant separately. The current research depicted this difference. Data from the current research would be useful in development of medication for dengue in future from female plant leaves. However, randomized clinical trials based on large scale are still needed in order to establish potentiating role of Carica papaya aqueous leaf extract, especially from female leaves, in the management and/or treatment of dengue and its associated complication.