Liu, Jingjing
(Department of Pharmaceutical analysis, School of Pharmacy, Ningxia Medical University, 1160 Shenli Street, Yinchuan 750004, China)
,
Zhang, Zhuanzhuan
(Department of Pharmaceutical analysis, School of Pharmacy, Ningxia Medical University, 1160 Shenli Street, Yinchuan 750004, China)
,
Guo, Qi
(Department of Pharmaceutical analysis, School of Pharmacy, Ningxia Medical University, 1160 Shenli Street, Yinchuan 750004, China)
,
Dong, Yanhong
(Department of Pharmaceutical analysis, School of Pharmacy, Ningxia Medical University, 1160 Shenli Street, Yinchuan 750004, China)
,
Zhao, Qipeng
(Department of Pharmaceutical analysis, School of Pharmacy, Ningxia Medical University, 1160 Shenli Street, Yinchuan 750004, China)
,
Ma, Xueqin
(Department of Pharmaceutical analysis, School of Pharmacy, Ningxia Medical University, 1160 Shenli Street, Yinchuan 750004, China)
Abstract Background Syringin, also called eleutheroside B, is a main bioactive phenolic glycoside in Acanthopanax senticosus (Rupr. et Maxim.) Harms. Based on the “kidney dominates bone” theory of TCM, A. senticosus can strengthen bone and Syringin may be one of the responsibilities. ...
Abstract Background Syringin, also called eleutheroside B, is a main bioactive phenolic glycoside in Acanthopanax senticosus (Rupr. et Maxim.) Harms. Based on the “kidney dominates bone” theory of TCM, A. senticosus can strengthen bone and Syringin may be one of the responsibilities. Purpose The objectives of this study were to estimate the osteoporotic activity of Syringin and reveal the possible molecular mechanisms in vivo. Methods Sixty female ICR mice were randomly assigned into sham operated group (SHAM, treated with vehicle) and five ovariectomized subgroups (n = 10 each), treated with vehicle as OVX group, estradiol valerate (EV, 1 mg/kg/day) as positive group, and Syringin (10, 20 and 40 mg/kg/day) as low, moderate and high dosage groups. The therapeutic effect of Syringin against osteoporosis was systematically analyzed by determining the bone mineral density (BMD), bone biomechanical properties, bone microarchitecture and serum biochemical parameters, and the molecular mechanism was also evaluated. Results After three months of orally administrated intervention, Syringin (10, 20 and 40 mg/kg/day) significantly improved the BMD, bone maximum load and trabecular bone microarchitecture in ovariectomized mice, evidenced by the increased bone mineral content, tissue mineral content, tissue mineral density, trabecular thickness and trabecular number, as well as the decreased trabecular separation in OVX mice. Meanwhile, the activities of tartrate-resistant acid phosphatase, deoxypyridinoline and cathepsin K in OVX mice were also inhibited by Syringin, while the increased body weight and decreased uterus weight seemed not influenced by Syringin administration. Concerning the underlying molecular mechanisms, Syringin significantly downregulated the expression of tumor-necrosis factor receptor-associated factor 6 (TRAF6), nuclear factor kappa B (NF-κB) and receptor activator of nuclear factor kappa B ligand (RANKL) proteins levels, upregulated the expression of osteoprotegerin (OPG), phosphoinositide 3-kinase (PI3K) and protein kinase B (AKT) levels, suggesting that Syringin prevented bone lost by TRAF6-mediated inhibition of NF-κB and stimulation of PI3K/AKT, and subsequently increasing the OPG/RANKL ratio and inhibiting the osteoclastogenesis, finally promoting bone formation. Conclusions All of the data implied Syringin possessed the potent anti-osteoporosis activity on ovariectomized mice, and the underlying molecular mechanism may be related to the NF-κB and PI3K/AKT signaling pathways. Graphical abstract [DISPLAY OMISSION]
Abstract Background Syringin, also called eleutheroside B, is a main bioactive phenolic glycoside in Acanthopanax senticosus (Rupr. et Maxim.) Harms. Based on the “kidney dominates bone” theory of TCM, A. senticosus can strengthen bone and Syringin may be one of the responsibilities. Purpose The objectives of this study were to estimate the osteoporotic activity of Syringin and reveal the possible molecular mechanisms in vivo. Methods Sixty female ICR mice were randomly assigned into sham operated group (SHAM, treated with vehicle) and five ovariectomized subgroups (n = 10 each), treated with vehicle as OVX group, estradiol valerate (EV, 1 mg/kg/day) as positive group, and Syringin (10, 20 and 40 mg/kg/day) as low, moderate and high dosage groups. The therapeutic effect of Syringin against osteoporosis was systematically analyzed by determining the bone mineral density (BMD), bone biomechanical properties, bone microarchitecture and serum biochemical parameters, and the molecular mechanism was also evaluated. Results After three months of orally administrated intervention, Syringin (10, 20 and 40 mg/kg/day) significantly improved the BMD, bone maximum load and trabecular bone microarchitecture in ovariectomized mice, evidenced by the increased bone mineral content, tissue mineral content, tissue mineral density, trabecular thickness and trabecular number, as well as the decreased trabecular separation in OVX mice. Meanwhile, the activities of tartrate-resistant acid phosphatase, deoxypyridinoline and cathepsin K in OVX mice were also inhibited by Syringin, while the increased body weight and decreased uterus weight seemed not influenced by Syringin administration. Concerning the underlying molecular mechanisms, Syringin significantly downregulated the expression of tumor-necrosis factor receptor-associated factor 6 (TRAF6), nuclear factor kappa B (NF-κB) and receptor activator of nuclear factor kappa B ligand (RANKL) proteins levels, upregulated the expression of osteoprotegerin (OPG), phosphoinositide 3-kinase (PI3K) and protein kinase B (AKT) levels, suggesting that Syringin prevented bone lost by TRAF6-mediated inhibition of NF-κB and stimulation of PI3K/AKT, and subsequently increasing the OPG/RANKL ratio and inhibiting the osteoclastogenesis, finally promoting bone formation. Conclusions All of the data implied Syringin possessed the potent anti-osteoporosis activity on ovariectomized mice, and the underlying molecular mechanism may be related to the NF-κB and PI3K/AKT signaling pathways. Graphical abstract [DISPLAY OMISSION]
Osteoporosis Int. Aubin 11 905 2000 10.1007/s001980070028 Osteoprotegerin and its ligand: a new paradigm for regulation of osteoclastogenesis and bone resorption
Tissue Eng. Part A Chen 19 2226 2013 10.1089/ten.tea.2012.0469 PI3K/AKT pathway involvement in the osteogenic effects of osteoclast culture supernatants on preosteoblast cells
J. Bone. Miner. Res. Eddleston 24 1662 2009 10.1359/jbmr.090403 A short treatment with an antibody to sclerostin can inhibit bone loss in an ongoing model of colitis
J. Bone. Miner. Res. Gorman 12 1761 2002 Prevalence of low femoral bone densityin older U.S. adults from NHANES III
J. Bone. Miner. Res. Hwang 27 584 2009 10.1007/s00774-009-0093-3 The effects of Acanthopanax senticosus extract on bone turnover and bone mineral density in Korean postmenopausal women
J. Bone. Miner. Res. Li 26 644 2011 10.1002/jbmr.242 Maslinic acid suppresses osteoclastogenesis and prevents ovariectomy-induced bone loss by regulating RANKL-mediated NF-kappaB and MAPK signaling pathways
Endocr. Rev. Suda 20 345 1999 10.1210/edrv.20.3.0367 Modulation of osteoclast differentiation and function by the new members of the tumor necrosis factor receptor and ligand families
JAMA-J. Am. Med. Assoc. Villareal 286 815 2001 10.1001/jama.286.7.815 Bone mineral density response to estrogen replacement in frail elderly women: a randomized controlled trial
Molecules Xu 197 1 2017 Therapeutic effect of cistanoside A on bone metabolism of ovariectomized mice
Phytomedicine Ye 22 94 2015 10.1016/j.phymed.2014.11.004 Antiosteoporotic activity and constituents of Podocarpium podocarpum
AI-Helper
※ AI-Helper는 부적절한 답변을 할 수 있습니다.