Dose- and Time-Dependent Effects of a Ferula communis Extract on Bone Remodelling in a Human Osteosarcoma Cell Line

Abstract

Ferula communis is a herbaceous plant in the family Apiaceae and order Apiales. It has two chemotypes that cannot be distinguished botanically, although one is highly toxic while the other is not. The non-poisonous chemotype has many beneficial activities for human health, including antioxidant, anti-inflammatory, cytotoxic, antimycobacterial, antiproliferative, neuroprotective, and estrogenic properties, thanks to its numerous secondary metabolites. This manuscript evaluates the effects of a Ferula communis extract on bone remodelling in a human osteosarcoma cell line. The extract from Ferula communis (FER-E) comes from the roots of the plant and, after chemically removing toxic ferulenol, further chromatographic analysis allowed us to estimate the ferutinin content, titrated at 25%. Saos-2 cells were treated with FER-E for both short times (24, 48, and 72 h) and longer times (up to 20 days) and, at each time, three aspects were evaluated: (a) cell viability; (b) cytosolic calcium concentration; and (c) the expression of specific proteins (OPG-RANKL) related to bone remodelling. The results were encouraging, suggesting that FER-E effects were dose- and time-dependent. Furthermore, both short and prolonged treatments positively modulated bone structure maintenance. For example, treatment with FER-E for 72 h preserves osteoblastic activity, presumably at the expense of osteoclastic activity. Treatment for 12 days seems to turn off this activity. Still, surprisingly, in a time window between the thirteenth and twentieth day, the cells produce one or more late compounds, capable of returning to the extract the ability to activate osteoblastic activity again. If these findings are properly confirmed, both in vitro and in vivo, Ferula communis could be associated with the delicate mechanism of bone remodelling.