Research progress on the interaction of artemisinin and its derivatives with TLR4 receptors in neuroinflammation

In recent years, TLR4, as a key member of the TLRs family, has attracted increasing attention for its role in neuroimmune diseases. As a critical immune surveillance molecule, TLR4 is considered a promising target for the modulation of neuroimmune disorders. A growing body of research has confirmed that artemisinin and its derivatives, as natural immunomodulators, participate in the regulation of TLR signaling pathways-particularly showing a close relationship with TLR4 among the TLR family.Recent studies have revealed a novel dual regulatory effect of artemisinin and its derivatives on the TLR4 signaling pathway. These compounds can not only selectively modulate TLR4-mediated inflammatory signaling cascades, such as the NF-κB pathway, effectively suppressing the excessive activation of microglia, but also inhibit TLR4 dimerization and endocytosis, thereby blocking downstream signal transduction and alleviating neuroinflammatory responses. This novel finding provides a molecular basis for targeting TLR4 in the treatment of neuroimmune diseases such as multiple sclerosis (MS) and Alzheimer's disease (AD).Moreover, as naturally derived TLR4 modulators, artemisinin and its derivatives show great potential as new lead compounds for targeted therapies in neuroimmune diseases, offering new avenues and strategies for treatment. Therefore, this review focuses on the molecular structural characteristics of artemisinin and its derivatives, and the TLR4-mediated signaling pathways. It explores their potential mechanisms of action in modulating neuroimmune disorders from multiple perspectives-including drug structural properties, molecular docking simulations, and target regulation. The objective is to identify safe and effective neuroimmune modulators from natural products and provide new research perspectives and strategies for the TLR4-targeted treatment of neuroimmune diseases.