Diterpenoids from the Chinese liverwort Frullania hamatiloba and their Nrf2 inducing activities

Abstract Six previously undescribed labdane diterpenoids, frullanians A−F, along with five known diterpenoids, were isolated from the Chinese liverwort Frullania hamatiloba Stephani . Their structures were determined using NMR data, electronic circular dichroism (ECD) calculations as well as the single crystal X-ray diffraction measurement. NAD(P)H: QR (quinone reductase) assay demonstrated that frullanian D and four known compounds displayed antioxidant effect mediated via Nrf2 (Nuclear factor-erythroid 2-related factor 2) induction. Further investigation of the most bioactive frullanian D in MOVAS cells revealed that it ameliorated H 2 O 2 -induced oxidative insults without toxicity by increasing cell viability, attenuating morphological changes, and reducing intracellular ROS production. In addition, frullanian D promoted the nuclear translocation of Nrf2 and upregulated the expressions of antioxidant proteins NQO1 (NAD(P)H quinone oxidoreductase 1) and γ-GCS (γ-glutamyl cysteine synthetase). Docking analysis using MOE software further supported the activation of the Nrf2 pathway by frullanian D.