Effects of total lignans from Eucommia ulmoides barks prevent bone loss in vivo and in vitro.
BACKGROUND
The present study systematically investigate the in vivo and in vitro effect of total lignans (TL) extracted from Eucommia ulmoides Oliv. barks on bone formation using ovariectomy rat model and primary cultures of rat osteoblasts.


METHODS
Eighty 3-month-old female Sprague-Dawley rats were used and randomly assigned into sham-operated group (SHAM) and five ovariectomy (OVX) subgroups, i.e. OVX with vehicle (OVX); OVX with 17α-ethinylestradiol (E2, 25 μg/kg/day); OVX with TL of graded doses (20, 40, or 80 mg/kg/day). The treatment began 4 weeks after the surgery and lasted for 16 weeks. in vitro experiments were performed to determine the potential mechanisms of the anti-osteoporotic effect of TL.


RESULTS
Treatment with TL significantly prevent OVX-induced decrease in biomechanical quality of femur such as maximum stress and Young׳s modulus. The mechanical changes were associated with the prevention of a further BMD decrease or even with some improvements in microarchitecture. TL inhibited BMD decrease in the femur caused by OVX, which was accompanied by a significant decrease in skeletal remodeling, as was evidenced by the decreased levels of the bone turnover markers. μCT analysis of the femoral metaphysis showed how to prevent the deterioration of trabecular microarchitecture. TL induced primary osteoblastic cell proliferation and differentiation, inhibition of osteoclastogenesis through an increase in osteoprotegrin (OPG) and a decrease in NF-κB ligand (RANKL) expression in vitro.


CONCLUSIONS
We concluded that TL treatment can effectively suppress the loss of bone mass induced by OVX and in vitro evidence suggests this could be through actions on both osteoblasts and osteoclasts.
Institute of Neurosurgery, Xijing Hospital, Fourth Military Medical University, Xi׳an 710032, China.
Rong
R
Zhang
School of Life Science, Northwestern Polytechnical University, Xi׳an 710072, China.
Ya-Lei
YL
Pan
Department of Pharmacology, School of Pharmacy, Fourth Military Medical University, Xi׳an 710032, China.
Shi-Jie
SJ
Hu
School of Life Science, Northwestern Polytechnical University, Xi׳an 710072, China.
Xiang-He
XH
Kong
School of Life Science, Northwestern Polytechnical University, Xi׳an 710072, China.
Wang
W
Juan
Department of Pharmacology, School of Pharmacy, Fourth Military Medical University, Xi׳an 710032, China; School of Life Science, Northwestern Polytechnical University, Xi׳an 710072, China. Electronic address: qbmei@fmmu.edu.cn.
Qi-Bing
QB
Mei
D000818:Animals; D015519:Bone Density / Q000187:drug effects*; D016723:Bone Remodeling / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D031283:Eucommiaceae / Q000737:chemistry*; D005260:Female; D017705:Lignans / Q000008:administration & dosage / Q000302:isolation & purification / Q000494:pharmacology*; D010006:Osteoblasts / Q000187:drug effects / Q000378:metabolism; D010010:Osteoclasts / Q000187:drug effects / Q000378:metabolism; D010012:Osteogenesis / Q000187:drug effects; D010024:Osteoporosis / Q000517:prevention & control*; D010052:Ovariectomy; D053245:RANK Ligand / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley
D017705:Lignans; D053245:RANK Ligand
Eucommia ulmoides Oliv. total saponins; Osteoblast; Osteoporosis; Ovariectomy