Tirucallane Triterpenoids from the Stems and Stem Bark of Cornus walteri that Control Adipocyte and Osteoblast Differentiations

Cornus walteri Wanger (Cornaceae) has been broadly used in traditional East Asian medicine for the treatment of various disorders, including skin inflammation and diarrhea. As part of our efforts to identify structurally and/or biologically new compounds from Korean medicinal plants, we have explored potentially new bioactive constituents from C. walteri. In the present study, seven triterpenoids (1-7) were isolated from C. walteri stems and stem bark. Compounds 1-3 were new tirucallane triterpenoids (cornusalterins N-P) and compounds 4-7 were isolated for the first time from C. walteri. The structures of the new compounds were determined based on 1D and 2D NMR spectroscopic data interpretations and HR-ESIMS, as well as a computational method coupled with a statistical procedure (DP4+). The regulatory effects of the isolated triterpenoids (1-7) on mesenchymal stem cell (MSC) differentiation to adipocytes and osteoblasts were examined in the C3H10T1/2 cell line. Although these compounds had little effect on MSC differentiation to osteoblasts, lipid droplet formation in adipocyte-differentiated MSCs decreased in the presence of the seven triterpenoids. Compounds 1 and 4 each had a relatively distinct correlation between dose and efficacy, showing adipogenesis suppression at higher concentrations. Our findings demonstrate that the active compounds 1 and 4 can exert beneficial effects in regulation of adipocyte differentiation.