Self-assembled baicalein-2,4-decadienal nanomedicine synergistically inhibits PGE2 expression and elicits anti-inflammatory responses

To explore novel anti-inflammatory strategies by targeting prostaglandin E2 (PGE2) overexpression, aiming to overcome the limitations of conventional cyclooxygenase-1/2 (COX-1/2) inhibitors such as nonsteroidal anti-inflammatory drugs (NSAIDs). A correlation analysis of the anti-inflammatory activities of 24 exterior- releasing herb medicines, including NF- κ B, COX2, and PGE2 activities, was conducted, and the key active ingredients in the herbs showing significant associations were screened. Using a self-assembly technique, baicalein-2,4-decadienal (BD) were formulated into stable and homogeneous carrier-free nanoparticles to enhance drug solubility and targeting. Subsequently, disease models associated with PGE2 overexpression—fever, pneumonia and rheumatoid arthritis were established to evaluate the antipyretic, analgesic and anti-inflammatory properties of BD nanomedicines. Their targeting capability and drug release profile were also investigated. BD nanomedicines exhibited a synergistic inhibitory effect on PGE2 production by concurrently targeting COX2 and microsomal prostaglandin E synthase-1 (mPGES1), thereby producing antipyretic, analgesic, and anti-inflammatory effects superior to those observed with either agent alone. Furthermore, BD nanoparticles demonstrated preferential accumulation in macrophages implicated in the inflammatory response and facilitated pH-responsive drug release within the inflammatory microenvironment. This targeted delivery approach not only enhances therapeutic efficacy but also enables dose reduction and mitigates the risk of adverse effects, representing a promising strategy for the treatment of PGE2-mediated inflammatory diseases. The findings provide new insights into drug development for inflammatory diseases caused by PGE2 overexpression, emphasizing the advantages of carrier-free supramolecular bioactive materials derived from natural products in the treatment of such diseases.