Casbane diterpenoids from Euphorbiaceae suppresse neuroinflammation by regulating microglia polarization via inhibiting NF-κB signaling.

Phytochemical investigation of Triadica rotundifolia and Neoshirakia japonica resulted in the discovery of eight new casbane diterpenoid derivatives. The structures of all isolates were structurally characterized by comprehensive spectroscopic techniques, including UV, IR, NMR, MS, together with X-ray diffraction. Notably, compound 1 (6S,12R-dihydroxy-1S,2R-casba-3E,7E,10E-trien-5-one) exhibited potent inhibition of NO production in LPS-stimulated microglia. Subsequent experiments revealed that compound 1 markedly reduced pro-inflammatory cytokine secretion while inducing microglial polarization from M1 to M2 states, demonstrating consistent neuroprotective efficacy across both cellular and animal models. Further analysis showed that compound 1 disrupted the NF-κB signaling cascade by blocking both IκBα phosphorylation and subsequent p65 nuclear translocation in LPS-stimulated cells. This study represents the first report of casbane diterpenoids from T. rotundifolia and N. japonica, and the first example of anti-neuroinflammatory effect of casbane diterpenoids derived from terrestrial plant sources.