Abstract
BACKGROUND: Osteoporosis is a metabolic bone disease with a high mortality rate due to non-traumatic fractures. The risk of osteoporosis is increasing globally due to an increasing aging population. Current therapies are limited to delaying disease progression. Recently, the need to discover foods with osteogenic activity for the prevention and treatment of osteoporosis has been emphasized. We focused on bone formation via osteoblast differentiation, considering bone formation and resorption during bone homeostasis. Rubus tozawae Nakai ex J. Y. Yang (RL, Geoje raspberry) is a deciduous subshrub that has been traditionally eaten for its fruit. METHODS AND RESULTS: We identified the third subfraction of n-hexane fraction (RL-Hex-NF3) of RL, an endemic Korean plant with osteogenic activity, which increased bone density in ovariectomized mice, a representative animal model of osteoporosis, via the depletion of female hormones, which resulted from the increase in the osteoblast population. RL-Hex-NF3 induced osteoblast differentiation and the expression of osteogenic markers in MC3T3-E1 pre-osteoblasts. Seven compounds were identified from RL-Hex-NF3 using NMR spectroscopy. Of these, three compounds, namely, 3β-hydroxy-18α,19α-urs-20-en-28-oic acid, betulinic acid, and (1S,6R,7S)-muurola-4,10(14)-diene-15-ol, showed strong osteogenic activity. CONCLUSIONS: RL-Hex-NF3 and its compounds suppress bone loss via their osteogenic properties, suggesting that they could be a potent candidate to treat osteoporosis.