Sanggenon C

30217005

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.

Sanggenon C; osteoblast; osteoclast; osteoporosis; zebrafish

Sanggenon C Stimulates Osteoblastic Proliferation and Differentiation, Inhibits Osteoclastic Resorption, and Ameliorates Prednisone-Induced Osteoporosis in Zebrafish Model.

Wang H1, Feng T2, Guo D3, Zhang M4, Chen L5, Zhou Y6,7.

2018 Sep 13;

30032067

Pancreatic lipase (PL), a key enzyme responsible for the hydrolysis of triacylglycerides in the gastrointestinal tract, has been identified as the therapeutic target for the regulation of lipid absorption. In the present study, six major constituents from a famous Chinese herbal medicine Cortex Mori Radicis (also named sangbaipi in Chinese), have been collected and their inhibitory effects on PL have been carefully investigated and well characterized by a fluorescence-based assay. The results clearly demonstrated that all tested bioactive constituents from Cortex Mori Radicis including sanggenone C (SC), sanggenone D (SD), kuwanon C (KC), kuwanon G (KG), morin and morusin displayed strong to moderate inhibitory effects towards PL with the IC50 values ranging from 0.77?μM to 20.56?μM. Further investigations on inhibition kinetics demonstrated that SC, SD, KC and KG functioned as potent and mixed inhibitors against PL-mediated 4-MU oleate hydrolysis, with the Ki values less than 5.0?μM. Furthermore, molecular docking simulations demonstrated that SD (the most potent PL inhibitor from Cortex Mori Radicis) could create strong interaction with Ser152 (the key amino acid in the catalytic triad) of PL via hydrogen bonding. All these findings provided a new powerful evidence for explaining the hypolipidemic effect of Cortex Mori Radicis, also suggested that some abundant natural compounds in this herbal medicine could be served as lead compounds for the development of new PL inhibitors.

Copyright ? 2018 Elsevier Inc. All rights reserved.

Cortex Mori Radicis; Inhibitory effects; Pancreatic lipase; Sanggenone C; Sanggenone D

Natural constituents from Cortex Mori Radicis as new pancreatic lipase inhibitors

Hou XD1, Ge GB2, Weng ZM3, Dai ZR4, Leng YH1, Ding LL3, Jin LL1, Yu Y3, Cao YF5, Hou J6.

2018 Oct;