Anti-osteoporosis activity of Sanguinarine in preosteoblast MC3T3-E1 cells and an ovariectomized rat model.

Abstract

Sanguinarine, a benzophenanthridine alkaloid, has been previously demonstrated to exert antimicrobial, anti-inflammatory, and anti-tumor activities. A previous study has identified Sanguinarine as a potential drug candidate for osteoporosis treatment by computational bioinformatics analysis. This study further evaluated the effects of Sanguinarine on the differentiation of murine preosteoblast MC3T3-E1 cells and its anti-osteoporosis activity in an ovarietomized rat model. Sanguinarine treatment (0.25, 0.5, 1, and 2 µm) of MC3T3-E1 cells significantly increased alkaline phosphatase (ALP) activity and the phoshporalyation of AMP-activated protein kinase α subunit (AMPKα), but did not affect cell proliferation. The induction effects of Sanguinarine treatment (2 µm) on ALP activity, AMPKα phosphorylation, Smad1 phosphorylation, and the expression of three osteoblast differentiation-regulators (bone morphogenetic protein 2 [BMP2], osterix [OSX], and osteoprotegerin [OPG]) were partially reversed by Compound C treatment. More importantly, Sanguinarine treatment promoted bone tissue growth in an ovariectomized (OVX) osteoporosis rat model as evaluated by histological examination, micro-CT analysis, and serum parameter detection. In conclusion, these results indicate that Sanguinarine induces the differentiation of MC3T3-E1 cells through the activation of the AMPK/Smad1 signaling pathway. Sanguinarine can stimulate bone growth in vivo and may be an effective drug for osteoporosis treatment.