9r-(9alpha(z)-10alpha)-of-3--angeloyloxy-4--acetoxy-3--4--dihydroseselin and Osteoporosis

A decrease of bone mass is a major risk factor for fracture. Several natural products have traditionally been used as herbal medicines to prevent and/or treat bone disorders including osteoporosis. Praeruptorin A is isolated from the dry root extract of Peucedanum praeruptorum Dunn and has several biological activities, but its anti-osteoporotic activity has not been studied yet.. The effect of praeruptorin A on the differentiation of bone marrow-derived macrophages into osteoclasts was examined by phenotype assay and confirmed by real-time PCR and immunoblotting. The involvement of NFATc1 in the anti-osteoclastogenic action of praeruptorin A was evaluated by its lentiviral ectopic expression. Intracellular Ca(2+) levels were also measured.. Praeruptorin A inhibited the RANKL-stimulated osteoclast differentiation accompanied by inhibition of p38 and Akt signaling, which could be the reason for praeruptorin A-downregulated expression levels of c-Fos and NFATc1, transcription factors that regulate osteoclast-specific genes, as well as osteoclast fusion-related molecules. The anti-osteoclastogenic effect of praeruptorin A was rescued by overexpression of NFATc1. Praeruptorin A strongly prevented the RANKL-induced Ca(2+) oscillation without any changes in the phosphorylation of PLCγ.. Praeruptorin A could exhibit its anti-osteoclastogenic activity by inhibiting p38/Akt-c-Fos-NFATc1 signaling and PLCγ-independent Ca(2+) oscillation.

Topics: Acid Phosphatase; Calcium; Cell Differentiation; Coumarins; DNA Primers; Humans; Immunoblotting; Isoenzymes; Macrophages; MAP Kinase Signaling System; Molecular Structure; NFATC Transcription Factors; Oncogene Protein v-akt; Osteoclasts; Osteoporosis; Phospholipase C gamma; Proto-Oncogene Proteins c-fos; Real-Time Polymerase Chain Reaction; Tartrate-Resistant Acid Phosphatase