Abstract
Angelica sinensis (Oliv.) Diels is a widely-used traditional Chinese herbal medicine in treating osteoporosis. Ligustilide (LIG) is the main component of A. sinensis and is considered to be the most effective biologically active ingredient in this plant. LIG has been found to have multiple pharmacological activities, such as anti-atherosclerosis, neuroprotection, anticancer, anti-inflammatory and analgesic. However, little is known regarding its anti-osteoporotic effects. The aims of this study were to investigate any protective effect of LIG on bone formation. The results showed that LIG significantly ameliorated inhibition of bone formation in zebrafish caused by prednisolone. LIG promoted osteoblast differentiation, including that of the pre-osteoblastic cell line MC3T3-E1 and bone marrow mesenchymal stem cells. LIG greatly improved the viability of MC3T3-E1 cells exposed to H2O2, attenuated H2O2-induced apoptosis and increased the expression of Bcl-2. Furthermore, LIG treatment lead to marked activation of phosphorylated EGFR and ERK1/2. These effects could be obviously inhibited by blocking GPR30 signaling with the specific inhibitor G15. Collectively, the results reveal that GPR30 is a positive switch for LIG to increase bone formation via regulation of EGFR, and these results provide evidence for the potential of LIG to treat osteoporosis.
Highlights
Osteoporosis (OP) is a systemic bone disease characterized by decreased bone mass and degeneration of bone microstructure, resulting in increased fragility of bone, making it prone to fracture[1,2]
Our study demonstrated a pharmacological role of LIG in regulation of bone formation and bone mass
We found that LIG promotes OB differentiation and prevents pre-osteoblast apoptosis through the GPR30/epidermal growth factor receptor (EGFR) pathway
Summary
Osteoporosis (OP) is a systemic bone disease characterized by decreased bone mass and degeneration of bone microstructure, resulting in increased fragility of bone, making it prone to fracture[1,2]. Angelica sinensis (Oliv.) Diels has a long history of use in traditional herbal medicine. It is traditionally used for treating female disorders including irregular menstruation, amenorrhea and OP12. LIG has been reported to protect skeletal muscle cells, nerve cells, and endothelial cells from all sorts of damage and to have anti-osteoarthritis effects[17,18,19,20]. It is unclear whether the therapeutic effect of A. sinensis on OP is related to LIG. Our results provide new insights into the therapeutic mechanism of A. sinensis in OP, and provide a basis for its application in the treatment of OP
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