title: Therapeutic Effect of Cistanoside A on Bone Metabolism of Ovariectomized Mice.
abstract: Cistanoside A (Cis A), an active phenylethanoid glycoside isolated fromCistanche deserticolaY. 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.
authors.affiliation: Department of Pharmaceutical Analysis, School of Pharmacy, Ningxia Medical University, 1160 Shenli Street, Yinchuan 750004, China. 2241823@sina.com.|Key Laboratory of Hui Ethnic Medicine Modernization, Ministry of Education, 1160 Shenli Street, Yinchuan 750004, China. 2241823@sina.com.
authors.forename: Xiaoxue
authors.initials: X
authors.lastname: Xu
authors.affiliation: Department of Pharmaceutical Analysis, School of Pharmacy, Ningxia Medical University, 1160 Shenli Street, Yinchuan 750004, China. 15109604869@163.com.|Key Laboratory of Hui Ethnic Medicine Modernization, Ministry of Education, 1160 Shenli Street, Yinchuan 750004, China. 15109604869@163.com.
authors.forename: Zhuanzhuan
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of Pharmaceutical Analysis, School of Pharmacy, Ningxia Medical University, 1160 Shenli Street, Yinchuan 750004, China. wangwenpingg@sina.com.|Key Laboratory of Hui Ethnic Medicine Modernization, Ministry of Education, 1160 Shenli Street, Yinchuan 750004, China. wangwenpingg@sina.com.
authors.forename: Wenping
authors.initials: W
authors.lastname: Wang
authors.affiliation: Department of Pharmaceutical Analysis, School of Pharmacy, Ningxia Medical University, 1160 Shenli Street, Yinchuan 750004, China. huiqin_yao@163.com.|Key Laboratory of Hui Ethnic Medicine Modernization, Ministry of Education, 1160 Shenli Street, Yinchuan 750004, China. huiqin_yao@163.com.
authors.forename: Huiqin
authors.initials: H
authors.lastname: Yao
authors.affiliation: Department of Pharmaceutical Analysis, School of Pharmacy, Ningxia Medical University, 1160 Shenli Street, Yinchuan 750004, China. maxueqin217@126.com.|Key Laboratory of Hui Ethnic Medicine Modernization, Ministry of Education, 1160 Shenli Street, Yinchuan 750004, China. maxueqin217@126.com.
authors.forename: Xueqin
authors.initials: X
authors.lastname: Ma
mesh_terms: D000818:Animals; D015415:Biomarkers; D015519:Bone Density / Q000187:drug effects; D001862:Bone Resorption / Q000378:metabolism; D001842:Bone and Bones / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000378:metabolism* / Q000473:pathology; D000071556:Cancellous Bone / Q000000981:diagnostic imaging / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D002396:Catechols / Q000494:pharmacology*; D005260:Female; D006027:Glycosides / Q000494:pharmacology*; D055595:Mechanical Phenomena / Q000187:drug effects; D051379:Mice; D010012:Osteogenesis / Q000187:drug effects; D010024:Osteoporosis / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D010052:Ovariectomy; D055114:X-Ray Microtomography
chemical_list: D015415:Biomarkers; D002396:Catechols; D006027:Glycosides; C555977:cistanoside A
keywords: RANKL; TRAF6; antiosteoporotic; cistanoside A; ovariectomized mice