Phytocompounds from Justicia adhatoda as Potential Thrombopoietic Agents: Docking and Preclinical Evaluation with c-Mpl Receptor

Platelets are anucleate cellular fragments derived from megakaryocytes through a tightly regulated process of thrombopoiesis within the bone marrow. Thrombocytopenia, defined by reduced platelet counts, is a common hematological disorder associated with diverse clinical conditions including dengue, hepatic dysfunction, and chemotherapy-induced marrow suppression. This deficiency significantly elevates the risk of severe bleeding episodes. Current therapeutic strategies, such as platelet transfusion, remain the cornerstone of supportive care but are limited by short lifespan, alloimmunization, and risk of transfusion-related complications. Thrombopoietin (TPO), acting via the c-Mpl receptor, is the principal regulator of platelet production. Although synthetic TPO receptor agonists such as Eltrombopag have been introduced into clinical practice, their use is constrained by notable adverse effects, underscoring the need for safer alternatives.

In this study, we investigated the thrombopoietic potential of Justicia adhatoda (JA) using an integrated in silico, in vitro, and in vivo approach. Molecular docking of JA-derived phytocompounds with the c-Mpl receptor was performed, complemented by ADMET profiling and pathway analyses to assess pharmacological viability. Hematological and toxicological evaluations of JA extracts in a rat model further validated its biological activity and safety profile. Our findings highlight Justicia adhatoda as a promising candidate for development as a natural thrombopoietic agent, offering potential advantages over existing therapies. This integrated approach provides a foundation for future translational studies aimed at harnessing plant-derived compounds for safe and effective management of thrombocytopenia.