Brazilin From Biancaea sappan as a Multi-Target Candidate in Thalassaemia: Mechanistic Insights Into Iron Chelation, Antioxidant Activity, and Potential JAK2 Modulation

Abstract

Thalassaemia is a hereditary haemoglobinopathy characterised by impaired globin synthesis, resulting in ineffective erythropoiesis and systemic iron overload. While current management relies on blood transfusions and chelation, these often fail to address the underlying molecular signalling dysregulation that contributes to the disease's progression, such as the imbalance in erythropoietin production and the activation of inflammatory pathways. Brazilin, the primary homoisoflavonoid from Biancaea sappan L., presents a multifaceted therapeutic profile. This review synthesises evidence of brazilin's activity as a potent iron chelator and reactive oxygen species (ROS) scavenger and anti-inflammatory agent, while evaluating its potential as a novel JAK2 inhibitor. Molecular docking suggests brazilin may bind to the JAK2 ATP-binding pocket, though functional validation is still required. By modulating the erythroferrone (ERFE)–hepcidin (HAMP) axis, brazilin potentially restores iron homeostasis and mitigates splenomegaly. We further evaluate its pharmacokinetics and safety profile, highlighting low toxicity and high oral bioavailability. This positions brazilin as a promising lead candidate for thalassaemia adjunct treatment, warranting further in vivo validation.