Triptolide-mediated immunomodulation of macrophages: from pathophysiology to therapy.

BACKGROUND: Triptolide (TP), a potent bioactive compound from the Chinese herb Tripterygium wilfordii, demonstrates strong anti-inflammatory and immunosuppressive effects. Evidence indicates that TP modulates macrophage polarization and regulates inflammatory responses through multiple signaling pathways, exerting significant immunomodulatory effects in various diseases. OBJECTIVE: This review summarizes the immunomodulatory mechanisms of TP on macrophage function, with a focus on its therapeutic potential in diverse diseases. We also explore strategies to mitigate TP's toxicity, including formulation enhancements, targeted delivery, ligand conjugation, and structural modifications. Finally, we highlight the therapeutic utility and clinical progress of TP derivatives, offering insights into their broad clinical applications. RESULTS: TP modulates macrophage migration, polarization, phagocytosis, and the production of cytokines and chemokines, thereby alleviating various macrophage-centric diseases. Strategies to reduce TP's toxicity not only mitigate systemic adverse effects but also enhance therapeutic efficacy through macrophage-targeted delivery. The clinical progress of TP derivatives demonstrates their broad therapeutic potential. CONCLUSION: TP's macrophage-targeted immunomodulation shows promising therapeutic potential for macrophage-centric diseases. However, its limited clinical use due to poor water solubility and significant toxicity highlights the need for further research to develop effective toxicity-reduction strategies.