Chemical Characterization of Novel Natural Products from the Roots of Asian Rice (Oryza sativa) that Control Adipocyte and Osteoblast Differentiation

Oryza sativa L. is consumed globally as a staple food, and its roots have been used as a Korean and Chinese medical supplement for protection of the stomach and lungs and for amelioration of vomiting and fever. In our continuing search for biologically effective metabolites from Korean natural materials, we found that an EtOH extract of O. sativa root reciprocally regulated adipocyte and osteoblast differentiation. Chemical analysis of the EtOH extract using a bioassay-guided fractionation protocol led to the isolation and determination of two novel lignans, oryzativols A and B, responsible for these regulatory activities. Using 1D and 2D nuclear magnetic resonance spectroscopic analyses, high-resolution mass spectrometry, and circular dichroism analysis, the structures of the novel compounds were elucidated. We examined their effects on the regulation of mesenchymal stem cell differentiation. Treatment with oryzativol A in the human mesenchymal cell line C3H10T1/2 suppressed gene expression of peroxisome proliferator activated receptor γ, which resulted in a reduction in adipogenesis. Oryzativol A also enhanced the expression of Runx2 and cellular differentiation into osteoblasts in the same mesenchymal stem cell line.