Sesquiterphens (ferutinin and cynaropicrin) differently mod-ulate osteogenesis in zebrafish larvae.

Natural sesquiterpenes are increasingly investigated for their potential therapeutic properties. This study evaluated the embryo toxicity and osteogenic activity of purified ferutinin from Ferula communis and purified cynaropicrin from Cynara cardunculus, comparing them with their respective crude whole extracts. Zebrafish embryos were exposed to serial dilutions of the molecules and extracts to evaluate their effect on developmental toxicity and skeletal development by whole mount histochemical staining. Non-toxic doses of purified ferutinin (100 pg/mL) significantly accelerated bone mineralization in zebrafish embryos. This pro-osteogenic effect was evidentiated in both intramembranous and endochondral ossification, without altering total body length or cartilaginous structures. In contrast, the Ferula communis whole extract showed only low toxicity but failed to promote bone mineralization. Regarding cynaropicrin, the purified molecule exhibited a 100% mortality threshold above 10 μg/mL, while the Cynara cardunculus whole extract displayed modest toxicity at 10 μg/mL. Neither purified cynaropicrin nor the whole artichoke extract showed any significant osteogenic activity or developmental alterations at non-toxic concentrations. These findings demonstrate that purified ferutinin exerts a unique, potent, and specific pro-osteogenic effect on both intramembranous and endochondral ossification, an activity lost in the whole crude extract and not shared by cynaropicrin, which do not possess phytoestrogenic properties of ferutinin