Yang Ye
State Key Laboratory of Drug Research and Natural Products Chemistry Department, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai
Natural products play an important role in new drug discovery. As one of the most important types of natural compounds, diterpenoids have attracted considerable attentions due to their diversified structures and a spectrum of bioactivities such as anti-bacterial, anti-malarial, anti-inflammation, anti-cancer and so on. Searching for bioactive diterpenoids is still a hot topic in the field of natural products.
A systematic investigation of unique diterpenoids from a medicinal herb Podocarpus nagi has been carried out, resulting in the isolation of 44 nor-diterpenoid lactones with 16 of them being new, especially a novel binor-diterpenoid with dehydroxylation at C-7. Notably, most of isolated diterpenoid lactones displayed remarkable potency to increase LDL uptake in HepG2 cells at a concentration of 5 M. In vivo study further showed that nagilactone B, an abundant diterpene existing in this plant, dose-dependently decreased TC, TG, and LDL levels in high fat diet induced dyslipidemic hamsters. Mechanism study indicated nagilactone B exerted lipid-lowering effect by elevating LDLR mRNA and protein level. It is the first time to report anti-hyperlipidemic activity for naturally occurring diterpene lactones in vitro and in vivo. Nagilactone B represent a new type of compounds with promising lipid-lowering activity.