From Juanbi Qianggu formula to a self-assembled nanodrug: identifying macrophage repolarization candidates and developing a carrier-free system for enhanced anti-inflammatory efficacy

Modulating macrophage repolarization represents an effective therapeutic strategy for inflammatory diseases. Leveraging the proven clinical efficacy of Traditional Chinese Medicine (TCM), developing drugs that target macrophage repolarization offers a promising avenue for advancing treatment. In this study, we identified two macrophage repolarization candidates (bakuchiol and psoralidin) from 26 bioactive components of the Juanbi Qianggu Formula (JBQG). Capitalizing on their inherent self-assembly properties, we selected bakuchiol for its superior performance and engineered carrier-free bakuchiol-NPs through systematically optimizing the key parameters. The self-assembly process was driven primarily by hydrophobic forces, π-π stacking, and hydrogen bonding, enabled by the unique structure of the bakuchiol. The resulting bakuchiol-NPs possessed excellent colloidal stability and high cellular uptake efficiency. Furthermore, bakuchiol-NPs demonstrated superior anti-inflammatory activity relative to free bakuchiol or positive drugs (magnolol and dexamethasone), as evidenced by lower expressions of inflammatory biomarkers ( Il1b , Tnfa , NO, CD86, ROS and IL-6) and higher expression of anti-inflammatory biomarkers ( Arg1 and IL-10). In conclusion, we identified bakuchiol from JBQG as a macrophage repolarization candidate, and developed a carrier-free nano-formulation to substantially augment its anti-inflammatory activity. This work proposes a promising new strategy for treating inflammatory diseases.