Abstract
Cistanoside A (Cis A), an active phenylethanoid glycoside isolated from Cistanche deserticola Y. C. Ma, has received our attention because of its possible role in the treatment of osteoporosis. In the present study, we evaluated the effects of Cis A on an ovariectomized (OVX) mice model and investigated its underlying molecular mechanisms of action. After 12 weeks of orally-administrated intervention, Cis A (20, 40 and 80 mg/kg body weight/day) exhibited significant antiosteoporotic effects on OVX mice, evidenced by enhanced bone strength, bone mineral density and improved trabecular bone microarchitecture. Meanwhile, the activities of bone resorption markers, including tartrate-resistant acid phosphatase (TRAP), deoxypyridinoline (DPD) and cathepsin K, were decreased, and the bioactivity of bone formation marker alkaline phosphatase (ALP) was increased. Mechanistically, Cis A inhibited the expression of TNF-receptor associated factor 6 (TRAF6), an upstream molecule that is shared by both nuclear factor kappa-light chain enhancer of activated B cells (NF-κB) and phosphatidylinositol 3-kinase (PI3K)/Akt pathways and subsequently suppressed the levels of receptor activators of nuclear factor kappaB ligand (RANKL), downregulated the expression of NF-κB and upregulated osteoprotegerin (OPG), PI3K and Akt, which means Cis A possessed antiosteoporotic activity in ovariectomized mice via TRAF6-mediated NF-kappaB inactivation and PI3K/Akt activation. Put together, we present novel findings that Cis A, by downregulating TRAF6, coordinates the inhibition of NF-κB and stimulation of PI3K/Akt pathways to promote bone formation and prevent bone resorption. These data demonstrated the potential of Cis A as a promising agent for the treatment of osteoporosis disease.
Highlights
Osteoporosis, a systemic skeletal “silent killer”, has become a major health hazard afflicting over 2000 million people worldwide in recent years [1]
The results indicate that the increased bone strength in the OVX mice treated with Cistanoside A (Cis A) was due to an increased amount of bone and an enhancement of bone quality
Three-dimensional trabecular bone microarchitecture of mice measured by micro-CT (Figure 2 and Table 1) intuitively shows that the mice in the OVX group presented a notable reduction in the trabecular area and trabecular number when compared to the sham group, indicating that ovariectomy could induced a notably decrease in bone mass density (BMD, −46%), bone mineral content
Summary
Osteoporosis, a systemic skeletal “silent killer”, has become a major health hazard afflicting over 2000 million people worldwide in recent years [1] It is characterized by low bone mass density (BMD). For more than a millennium, traditional Chinese medicines (TCM), especially the edible TCM with the isolated bioactive compounds and fractions, have been extensively used safely and effectively in Asian countries to prevent and treat various diseases, including osteoporosis [6,7]. The present study was designed to validate the potential of Cis A in preventing osteoporosis by using an ovariectomized mice model, and bone formation and resorption markers, as well as the related potential mechanisms were determined to estimate the antiosteoporotic bioactivity of this agent
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