Lirispirolides A–L, a new class of sesquiterpene‐monoterpene heterodimers with anti-neuroinflammatory activity from the rare medicinal plant Liriodendron chinense

Lirispirolides A–L (1–12), twelve unprecedented sesquiterpene-monoterpene heterodimers with new carbon skeletons, were isolated from the branches and leaves of Chinese tulip tree (Liriodendron chinense), a rare medicinal and ornamental plant endemic to China. The new structures were determined by a combination of spectroscopic data analyses, quantum-chemical calculations, and X-ray crystallography. All the heterodimers feature a unique 2-oxaspiro4.5decan-1-one motif, which are biosynthetically constructed by the intermolecular 4 + 2-cycloaddition of a germacrane-type sesquiterpene and an ocimene-type monoterpene. Most of the isolates attenuated neuro-inflammation in lipopolysaccharide (LPS)-induced BV-2 microglial cells by decreasing the level of pro-inflammatory mediators including tumor necrosis factor-α (TNF-α) and nitric oxide (NO). The suppression of NO release by lirispirolides was further ascertained to be correlated with down-regulation of the mRNA expression of inducible nitric oxide synthase (iNOS).