Sanggenon C (SC), which is a natural flavonoid found in the stem bark of Cortex Mori, has been discovered to have the antioxidant, anti-inflammatory, and antitumor properties. However, its effect in osteoporosis has not yet been reported. In this research, the effect of SC on the proliferation of MC3T3-E1 cells was evaluated by using the MTT assay. Alkaline phosphatase (ALP) activity and the mRNA expression of Runx2, Collagen I, OPG, and RANKL were examined. TRAP-positive cell counting and bone resorption pits were adopted to observe the effect of SC on the formation and function of osteoclasts. Next, the mRNA level of TRAP, CTSK, NFATc1, and TRAF6 of osteoclasts were measured by real-time qPCR. In addition, the anti-osteoporosis activity of SC in vivo was evaluated in the zebrafish model. Our study indicated that SC exhibited a significant stimulatory effect on MC3T3-E1 cell proliferation at 1 to 10 μM and caused an increase in ALP activity at 0.3 to 10 μM. It could upregulate the expression of Runx2, Collagen I, and increases the OPG/RANKL ratio. Furthermore, SC was found to inhibit the formation and function of osteoclasts, which is demonstrated by a lower number of TRAP-positive multinuclear cells and a fewer area of bone resorption pits compared to the control group. TRAP, CTSK, and NFATc1 were downregulated in 0.3 to 10 μM SC treated groups. In addition, 3 to 10 μM SC also inhibited the expression of TRAF6 mRNA. When prednisone-induced zebrafish was treated with 0.3, 1, 3, and 10 μM SC, higher mineralization of vertebrate column was discovered in a dose-dependent pattern, which suggests that SC could reverse the bone loss of zebrafish caused by prednisone. In summary, these findings indicated that SC has the potential to prevent or treat osteoporosis.

Salicyloylbenzene/heterocycles are privileged scaffolds found in many natural products and bioactive molecules. Numerous useful approaches for the preparation of these privileged scaffolds have been developed in recent years. Among these...

Inspired by the chemistry and biology of butyrolactones, pyrrolidines and chromanones, herein we successfully developed a simple domino 1,3-dipolar cycloaddition of homoserine lactone-derived azomethine ylides for construction of biologically important spiro-[butyrolactone-pyrrolidine-chromanone] hybrids in the presence of the catalyst Et3N under mild conditions. It is based on the application of carboxylic acid activated chromones as dienophiles followed by a decarboxylation process. This reaction displayed good substrate tolerance and gave the desired products in moderate to good yields with high diastereoselectivities via an exo-transition state (up to 85% yield and >20:1 diastereomeric ratio). In particular, this is the first example of introduction of chromanone moiety into spiro [butyrolactone-pyrrolidine] frameworks, which might be valuable in medicinal chemistry.