Network pharmacology and protective effect of HPLC-PDA validated flavonoid rich Carica papaya for the treatment of thrombocytopenia

The dengue virus transmitted through mosquito bites causes a series of ailments ranging from mild-cold like symptoms to severe haemorrhagic fever or dengue shock syndrome, which can be fatal. One of the major clinical indicators of severe dengue infection is thrombocytopenia, a significant drop in platelet count Traditionally, Carica papaya leaf juice (CPLJ) has been regarded as a promising platelet enhancing remedy in dengue fever. The present study was aimed to systematically evaluate the untargeted metabolomic analysis of bioactive butanol fraction (BBF) of fresh CPLJ. For polyphenol quantification, HPLC analysis was used, followed by cytotoxicity studies in HepG2 and HEK 293 cell lines. Network pharmacological analysis was used to investigate the multi-mechanism of polyphenols in promoting platelet recovery in dengue. Six metabolites were identified and quantified by HPLC in both BBF and Bioactive ethanol fraction (BEF). The BBF and BEF showed relatively high cytotoxicity in HepG2 demonstrating inhibition whereas in HEK 293 cells, they promoted proliferation,exhibiting the highest IC₅₀ values. Further through network pharmacology, the six quantified phytocompounds demonstrated multiple physiological roles in dengue associated thrombocytopenia with an emphasis on their drug-like properties, and interactions with targetssuch as TLR4, RELA, MAPK1 etc. Thus, it was concluded that through interaction with TLR4, phytocompounds such as quercetin, trans ferulic acid, and kaempferol may serve as promising agents by reducing thrombocytopenia in dengue-infected individuals. These compounds can be used as drugs to treat dengue-associated thrombocytopenia after verifying their efficacy and drug potency through in-vitro assays. BBF and BEF can be used as phytopharmaceuticals for the enhancement of platelets, either as standalone treatments or adjuvants.