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Introduction
Osteoporosis is a medical and socioeconomic problem characterized by the loss of bone mass and mechanical properties, leading to an increased risk of fracture. A variety of factors may lead to osteoporosis, and menopause is one of the most common reasons (1). In postmenopausal women, decreased estrogen levels cause increased osteoclast formation and elevated bone resorption, resulting in more rapid bone loss (2). Therefore, targeting osteoclast formation and function is one of the strategies for preventing and treating osteoporosis. Currently, several drugs aimed at inhibiting osteoclast formation or function have been used for osteoporosis, including bisphosphonates and denosumab (3). Aside from these synthesized compounds or antibodies, natural compounds are alternative therapeutic agents for the prevention and treatment of osteoporosis. Several natural products have exhibited an anti-osteoporotic property, including berberine, kaempferol, formononetin and osthole (4–7). Our study group has a long-term interest in evaluating the pharmacological effect of natural compounds on osteoporosis (8–11). Sanguinarine [13-methyl-(1,3) benzodioxole (5,6-c)-1,3-dioxolane (4,5-I) phenanthridinium] is an alkaloid derived from the roots of Sanguinaria canadensis. Sanguinarine exhibits multiple pharmacological effects, including anti-inflammatory, antitumor, antimicrobial, antiplatelet and antihypertensive properties (12). The authors previously revealed that sanguinarine inhibited osteoclast formation and bone resorption by suppressing the tumor necrosis factor ligand superfamily member 11-induced nuclear factor-κB and extracellular signal-regulated kinase signaling pathways (10). However, whether this natural compound prevents estrogen deficiency-induced bone loss requires further investigation in vivo. Considering the potential of sanguinarine for suppressing osteoclast formation in vitro, and the wide use of this compound in traditional medicine, the present study was designed to investigate whether sanguinarine may protect against ovariectomy (OVX)-induced osteoporosis and, thus, be a potential agent for future clinical application.
Materials and methods
Ethics statement
The Animal Care and Experiment Committee of Zhejiang University School of Medicine (Zhejiang, China) approved all experimental procedures and the study was performed according to the guidelines for Ethical Conduct in the Care and Use of Nonhuman Animals in Research by the American Psychological Association (13).
Media and reagents
Sanguinarine, dimethyl sulfoxide (DMSO) and the tartrate-resistant acid phosphatase (TRAP) staining kit were purchased from Sigma-Aldrich (Merck KGaA, Darmstadt, Germany). Sanguinarine was dissolved in DMSO and was stored at −20°C. To prevent photosensitivity, the experiments were performed in the absence of visible light....