Matrine and oxymatrine: a comprehensive review of multitarget mechanisms and therapeutic potential.

In recent years, research of matrine (MAT) and oxymatrine (OMT) has shifted from merely discovering pharmacological activities to exploring mechanisms, expanding new indications, and improving formulations. However, comparative analyses of their similarities and differences remain limited. Beyond their well-known functions in cancer treatment-such as regulating non-coding RNAs, preventing metastasis, and triggering apoptosis and ferroptosis-these compounds also show notable immunomodulatory effects, particularly in synergizing with immune checkpoint inhibitors to enhance tumor responsiveness. Furthermore, they show efficacy in inflammatory and autoimmune diseases (e.g., colitis, psoriasis, encephalomyelitis), neuroprotection, cardioprotection, and anti‑fibrosis. To overcome limitations such as hepatotoxicity and poor bioavailability, significant progress has been made in the structural modification of MAT and in the advanced formulation of OMT, thereby enhancing potency, selectivity, and targeted delivery. This review systematically consolidates recent advances in their multitarget mechanisms and expanding their therapeutic landscape. It also provides a unified mechanism overview and highlights the transformation strategy. These collective efforts will improve our understanding of MAT and OMT, offering a valuable reference for the further development of these natural products into modern therapeutics.