TY - JOUR
T1 - Boldine isolated from Litsea cubeba inhibits bone resorption by suppressing the osteoclast differentiation in collagen-induced arthritis
AU - Zhao, Hongyan
AU - Xu, Huihui
AU - Qiao, Senyan
AU - Lu, Cheng
AU - Wang, Gui
AU - Liu, Meijie
AU - Guo, Baosheng
AU - Tan, Yong
AU - Ju, Dahong
AU - Xiao, Cheng
N1 - Funding Information:
This work was supported by the National Natural Science Foundation of China [grant numbers 81373773, 81573845, 81673844]; Beijing Natural Science Foundation [grant numbers 7142144]; International Cooperation Project of the Ministry of Science and Technology[grant number 2014DFA31490]; National Nonprofit Institute Research Grant for Institute of Basic Theory for Chinese Medicine, CACMS [grant numbers YZ-1405]; International Cooperation Project of the State Administration of Traditional Chinese Medicine (grant number GZYYGJ2017014).
PY - 2017/10
Y1 - 2017/10
N2 - Objective To investigate the effect of boldine isolated from Litsea cubeba on collagen-induced arthritis (CIA) rats and explore the molecular mechanism predicted by network pharmacology. Material and methods CIA rats were orally administered with boldine. The bone destruction of paws was analyzed by histologic examination, tartrate-resistant acid phosphatase (TRACP) staining and micro-computed tomography. Prediction of signal pathway associated with boldine network molecules and CIA genes was applied by the network pharmacology analysis. The expressions of osteoprotegerin (OPG), receptor activator of nuclear factor-κB (RANK) and its ligand (RANKL) in the ankle were detected by immunohistochemistry. In vitro osteoclasts were cultured in the presence of variable doses of boldine and the RANK expressions were evaluated using Real-time polymerase chain reaction and western blot. Results Boldine reduced ankle swelling, alleviated pathological damage and significantly prevented bone destruction in CIA rats. Consistent with this, enzyme linked immunosorbent assay revealed boldine decreased serum TRACP5b levels and osteoclast number in the ankle region by TRACP staining from CIA rats. The network pharmacology analysis indicated that RANK signaling in osteoclasts was the most significant canonical pathway associated with boldine network molecules and CIA genes, which was verified by the increased expression of OPG, reduced expression of RANK, RANKL and RANKL/OPG in boldine-treated CIA rats. The in vitro study further confirmed that boldine inhibited osteoclastogenesis by inhibiting the RANKL/RANK signaling pathway. Conclusion Taken together, our study first indicates that boldine from Litsea cubeba suppresses osteoclastogenesis, improves bone destruction by down-regulating the OPG/RANKL/RANK signal pathway and may be a potential therapeutic agent for rheumatoid arthritis.
AB - Objective To investigate the effect of boldine isolated from Litsea cubeba on collagen-induced arthritis (CIA) rats and explore the molecular mechanism predicted by network pharmacology. Material and methods CIA rats were orally administered with boldine. The bone destruction of paws was analyzed by histologic examination, tartrate-resistant acid phosphatase (TRACP) staining and micro-computed tomography. Prediction of signal pathway associated with boldine network molecules and CIA genes was applied by the network pharmacology analysis. The expressions of osteoprotegerin (OPG), receptor activator of nuclear factor-κB (RANK) and its ligand (RANKL) in the ankle were detected by immunohistochemistry. In vitro osteoclasts were cultured in the presence of variable doses of boldine and the RANK expressions were evaluated using Real-time polymerase chain reaction and western blot. Results Boldine reduced ankle swelling, alleviated pathological damage and significantly prevented bone destruction in CIA rats. Consistent with this, enzyme linked immunosorbent assay revealed boldine decreased serum TRACP5b levels and osteoclast number in the ankle region by TRACP staining from CIA rats. The network pharmacology analysis indicated that RANK signaling in osteoclasts was the most significant canonical pathway associated with boldine network molecules and CIA genes, which was verified by the increased expression of OPG, reduced expression of RANK, RANKL and RANKL/OPG in boldine-treated CIA rats. The in vitro study further confirmed that boldine inhibited osteoclastogenesis by inhibiting the RANKL/RANK signaling pathway. Conclusion Taken together, our study first indicates that boldine from Litsea cubeba suppresses osteoclastogenesis, improves bone destruction by down-regulating the OPG/RANKL/RANK signal pathway and may be a potential therapeutic agent for rheumatoid arthritis.
KW - Boldine
KW - Bone resorption
KW - Collagen-induced arthritis
KW - Litsea cubeba
KW - OPG/RANKL/RANK signaling pathway
KW - Osteoclast
UR - http://www.scopus.com/inward/record.url?scp=85027515102&partnerID=8YFLogxK
U2 - 10.1016/j.intimp.2017.08.013
DO - 10.1016/j.intimp.2017.08.013
M3 - Journal article
C2 - 28826044
AN - SCOPUS:85027515102
SN - 1567-5769
VL - 51
SP - 114
EP - 123
JO - International Immunopharmacology
JF - International Immunopharmacology
ER -
