Anti-inflammatory and anti-osteoclastogenic activity of a Crocus sativus petal extract targeting macrophages: from waste to raw material on the way to preventing bone loss.

to obtain saffron, a much-appreciated spice. Stigmas have been proved to be a source of antioxidant molecules, potentially exploitable in the health field, but actually not used because too expensive [1]. Nevertheless, also saffron petals, the main waste from stigmas harvesting, could be a valuable source of bioactive ingredients since they have shown protective effects in experimental models of inflammation and oxidative stress [2]. Thus, by in vitro models using RAW264.7 macrophages, we investigated the possible ability of a saffron petal dry extract (CsPE, Crocus sativus petal extract), rich in antioxidant compounds (i.e., quercetin, gallic acid, kaempferol), in restraining the production of inflammatory mediators and in contrasting the osteoclast formation. In the inflammatory model of RAW 264.7 treated with lipopolysaccharide (LPS), CsPE displayed anti-inflammatory activity, significantly reducing nitric oxide production and IL-6 release in a dose-dependent manner. Moreover, in the osteoclast formation model of RAW 264.7 stimulated with receptor activator of nuclear factor kappa-Β ligand (RANKL), CsPE demonstrated a potent anti-osteoclastogenic effect, as revealed by the dose-dependent strong decrease of both osteoclast number and osteoclast marker gene expression. The knowledge of anti-inflammatory and anti-osteoclastogenic effects evoked on macrophages targeted by the bioactive components contained in Crocus sativus petals could be translated and applied to a virtuous circular economy process transforming the waste of saffron harvesting into the raw material for the preparation of a phytotherapeutic product for the control of inflammation and bone loss diseases.