Withdrawal Notice: Synergistic Effect of Myricetin and Phenolic Acid Derivatives on the Reversal of Dengue Fever Related Thrombocytopenia and its Pharmacokinetics study in Plasma by using HPLC and UPLC-Q-TOF

Abstract

Background: Carica papaya L. is consumed worldwide because of its high nutritional and medicinal benefits due to the presence of polyphenols. Objective: The present study was undertaken to investigate the effects of polyphenols present in C. papaya in dengue fever against cyclophosphamide (CP) induced thrombocytopenia in balb/c mice. Method: Platelet count (PC), total leukocyte count (TLC), activated partial thromboplastin time (aPTT), prothrombin time (PT), anti-platelet antibodies IgG and IgM were analysed in blood/serum of animals treated for 21 days with standardized C. papaya leaf juice (CPLJ) and its bioactivity guided selected fractions (SFs). A new HPLC-PDA method was developed to study pharmacokinetic (PK) profile of phytoconstituents in plasma of bioactive butanol fraction (BBF) and CPLJ treated mice. CPLJ and BBF were metabolically distinguished by UPLC-qTOF/MS for metabolite signature. Results: Animals orally treated with BBF elicited significant reduction in blood/serum levels of aPTT, PT, AST, ALT and antibodies IgG and IgM. However, thrombocyte count was significantly (p<0.01) increased. A total of 12 and 9 metabolites were tentatively identified using UPLC-qTOF/MS in BBF and CPLJ, respectively. PK parameters evaluated by noncompartmental model showed Cmax of plant flavonoids and phenolic acids including caffeic acid, para-coumaric acid, vanillic acid, myricetin and trans-ferulic acid (0.10, 0.49, 0.61, 5.97, 36.29 µg/mL, respectively) and half-life (24, 6, 26, 15 and 13 h), respectively. Conclusion: Collectively, our data suggest that the polyphenol enriched fraction of CPLJ might reverse acute thrombocytopenia by accelerating the platelets regeneration from megakaryocytes, providing strong rational for its use in the treatment of dengue fever-related thrombocytopenia. Thus, the BBF can be used as phytopharmaceuticals for the enhancement of platelets by using as adjuvants or alone.