The Carica papaya plant has been shown to be useful in a wide range of therapeutic use from anthelmintic effect of its latex to the aphrodisiac property of its root. Carica papaya leaves (CPL) is a popular remedy to treat dengue-induced thrombocytopaenia. This study was designed to explore the preliminary phytochemical analysis of CPL aqueous and methanol extracts. In this study flavonoids and phenolics were characterized by LC - TOF- MS, in which 19 compounds were detected in aqueous extract and 24 compounds were detected in methanol extract. This knowledge may help us devise better formulations to develop CPL into useful therapeutic agents for the management of thrombocytopaenia related disorders.

Dengue fever is endemic in tropical urban developing regions worldwide. Thrombocytopenia is an important clinical feature which may result in bleeding. However, there is no specific treatment for Dengue-induced thrombocytopenia. Carica papaya leaves (CPL) is a popular remedy in South East Asia to treat Dengue-induced thrombocytopenia. Development of CPL into pharmaceutical therapeutic agents is not forthcoming due to lack of rigorous scientific evidence and unknown mechanism of action. This study investigated the role of thrombopoietin (TPO) and interleukin (IL-6) in the thrombocytosis effect of CPL in vivo. These experiments were conducted using busulfan-induced thrombocytopenic rats. Treatment of aqueous and methanol extracts of CPL at 600mg/kg were administered orally for 7 consecutive days and serum platelet count was determined intermittently until day 15. At the end of experiments, serum Thrombopoietin (TPO) and IL-6 levels were determined by ELISA. Both aqueous and methanol extracts of CPL significantly increased platelet count compared to the control groups (x2 (2) = 25.373, P = 0.00). Investigations into the mechanism of thrombocytosis showed that TPO and IL-6 levels were increased compared to controls but was not statistically significant (H (3) = 5.339 P = 0.149) (H (3) = 4.412 P = 0.220) respectively. This study is the first to document the thrombocytosis effect of both aqueous and methanol CPL extracts in a rodent model system. Our findings showed that aqueous extract of CPL demonstrated an increase of TPO and IL-6 levels. We suggested that the possible mechanism could be linked with the upregulation of major thrombopoietic cytokines such as TPO and IL-6

Previous studies have shown platelets play an important role in prothrombotic complications due to several factors such as hyperglycemia, oxidative stress, and hypercholesterolemia, which affected platelets reactivity. Platelets activation involves ADP stimulation via P2Y12 receptor, whereas reactive oxygen species (ROS) including superoxide anion and hydrogen peroxide (H2O2) produced by NADPH oxidase (Nox) act as the second messenger, which involved in platelets activation and may contribute to thrombus formation. The aim of the present study was to investigate the influence of Nox on the purinergic receptor (P2Y12 receptor) in activation of human platelets function stimulated by platelets agonist. This research explored the effects of Nox inhibitors and clopidogrel either alone or in combination, on various agonist-stimulated human platelets, including platelets aggregation and adhesion measured by modified LTA, expression of platelets activation markers, and calcium mobilization using flow cytometry, and ROS formation, NADPH oxidase activity, as well as cAMP levels by chemiluminescence assay. Taken together, findings from these experiments suggest that the combination of clopidogrel and Nox inhibitors synergistically reduced platelets aggregation, platelets adhesion, and expression of platelets activation marker during late activation, ROS formation, NADPH oxidase activity, calcium mobilization and increased cAMP levels in vitro. This combination showed that P2Y12receptor reactivity was influenced by the activation of NADPH oxidase. Thus, these data demonstrated a potential combination therapy to reduce the risk of thrombosis formation.