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Molecules 2017, 22(2), 197; doi:10.3390/molecules22020197

Therapeutic Effect of Cistanoside A on Bone Metabolism of Ovariectomized Mice

1,2,†
,
1,2,†
,
1,2
,
1,2
and
1,2,*
1
Department of Pharmaceutical Analysis, School of Pharmacy, Ningxia Medical University, 1160 Shenli Street, Yinchuan 750004, China
2
Key Laboratory of Hui Ethnic Medicine Modernization, Ministry of Education, 1160 Shenli Street, Yinchuan 750004, China
Both authors contributed equally to this work.
*
Author to whom correspondence should be addressed.
Academic Editor: Dong-Kug Choi
Received: 9 January 2017 / Revised: 20 January 2017 / Accepted: 20 January 2017 / Published: 24 January 2017
(This article belongs to the Special Issue Natural Products and Chronic Diseases)
View Full-Text   |   Download PDF [5858 KB, uploaded 24 January 2017]   |  

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. View Full-Text
Keywords: cistanoside A; ovariectomized mice; antiosteoporotic; TRAF6; RANKL cistanoside A; ovariectomized mice; antiosteoporotic; TRAF6; RANKL
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Xu, X.; Zhang, Z.; Wang, W.; Yao, H.; Ma, X. Therapeutic Effect of Cistanoside A on Bone Metabolism of Ovariectomized Mice. Molecules 2017, 22, 197.

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