Mechanisms of Macrophage Polarization Regulated by Oridonin: A Review.

Oridonin(Ori), a natural ent-kaurane diterpenoid derived from the medicinal herb Rabdosia rubescens, has garnered significant interest for its potent anti-inflammatory and immunomodulatory properties. A key mechanism underlying these effects is its ability to regulate polarization. This review elaborates on the multifaceted mechanisms by which Ori modulates macrophage, extending beyond the inhibition of pro-inflammatory signaling pathways. We highlight its emerging role in metabolic reprogramming by shifting the functional balance from a pro-inflammatory M1 phenotype towards an anti-inflammatory and tissue-reparative M2 phenotype. Ori exhibits therapeutic potential not only in cancer and but also in a broad spectrum of other conditions, including non-alcoholic fatty liver disease, rheumatoid arthritis, colitis, asthma, atherosclerosis, and sepsis. However, the clinical translation of Ori is severely hampered by its unfavorable pharmacokinetic properties, such as poor aqueous solubility and low oral bioavailability. We conclude by discussing future perspectives, emphasizing the need for advanced drug delivery systems, the integration of multi-omics technologies to thoroughly map macrophage responses, and the application of network pharmacology and artificial intelligence to propel the rational development of oridonin as a novel macrophage-centric therapeutic agent.