Guaiane sesquiterpenes from Lindera glauca: isolation, structural elucidation, and hepatoprotective effect

Nine undescribed guaiane sesquiterpenoids named linderaguaianoids A-I, together with thirteen reported analogues, were isolated from the roots of Lindera glauca. Their structures were fully elucidated by spectroscopic techniques, single-crystal X-ray diffraction experiments, and quantum chemical calculations. Linderaguaianoid A is characterized as a rare 5/5/6/5-caged tetracyclic sesquiterpenoid with a [5.3.1.1^4,11.0^1,5]dodecane scaffold. Linderaguaianoids B-C and E are uncommon guaiane-type norsesquiterpenoids. Among these compounds, pseudoguaianelactone A inhibits hypoxia-inducible factor-1α activity, suppresses macrophage-mediated inflammatory response, and alleviates liver injury in LPS/D-GalN-induced acute liver injury mice, suggesting that it may emerge as a potent lead for the development of therapeutic agent against acute liver injury.