Development of 3-mercaptopropyltrimethoxysilane(MPTS)-modified bone marrow mononuclear cell membrane chromatography for screening anti-osteoporosis components from Scutellariae Radix  

作　　者：Yanqiu Gu Xiao Chen Yao Wang Yue Liu Leyi Zheng Xiaoqun Li Rong Wang Shaozhan Wang Shengnan Li Yifeng Chai Jiacan Su Yongfang Yuan Xiaofei Chen 

机构地区：[1]Department of Pharmacy,Shanghai Ninth People’s Hospital,Shanghai Jiao Tong University,School of Medicine,Shanghai 201999,China [2]School of Pharmacy,Second Military Medical University,Shanghai 200433,China [3]Department of Orthopedic Trauma,Shanghai Changhai Hospital,Second Military Medical University,Shanghai 200433,China

出　　处：《Acta Pharmaceutica Sinica B》2020年第10期1856-1865,共10页药学学报（英文版）

基　　金：supported by the National Natural Science Foundation of China(Grant Nos.81973291 to Xiaofei Chen,81573396 to Yifeng Chai,81973275 to Yongfang Yuan,81703674 to Yue Liu,81703779 to Rong Wang,81803815 to Shaozhan Wang and 81871099 to Xiao Chen);Fund of Shanghai Science and Technology Committee,China(19QA1411500 to Xiaofei Chen,17401900800 to Yongfang Yuan and 17YF1424700 to Yue Liu)

摘　　要：Osteoporosis is a bone metabolic disease caused by the imbalance between osteoblasts and osteoclasts due to excess osteoclastogenesis,manifesting in the decrease of bone density and bone strength.Scutellariae Radix shows good anti-osteoporosis activity,but the effective component is still unclear.Cell membrane chromatography(CMC)is a biological affinity chromatography with membrane immobilized on a silica carrier as the stationary phase.It can realize a dynamical simulation of interactions between drugs and receptors on cell membrane,which is suitable for screening active compounds from complex systems.In this study,the components of Scutellariae Radix with potential anti-osteoporosis activity through inhibiting the differentiation from bone marrow mononuclear cells(BMMCs)to osteoclast were screened by a BMMC/CMC analytical system.Firstly,a new3-mercaptopropyltrimethoxysilane(MPTS)-modified BMMC/CMC stationary phase was developed to realize covalent binding with cell membrane fractions.By investigating the retention time(tR)of the positive drug,the life span of the MPTS-modified CMC columns was significantly improved from 3 to 12 days.Secondly,6 components of Scutellariae Radix were screened to show affinity to membrane receptors on BMMCs by a two-dimensional BMMC/CMC-TOFMS analytical system.Among them,tectochrysin demonstrated the best anti-osteoporosis effect in vitro,which has never been reported.We found that tectochrysin could inhibit the differentiation of BMMCs into osteoclasts induced by receptor activator of nuclear factor-κB ligand(RANKL)and macrophage colony-stimulating factor(M-CSF)in a concentration-dependent manner in vitro.In vivo,it significantly reduced the loss of bone trabeculae in ovariectomized mice,and decreased the level of C-terminal cross-linking telopeptides of type 1 collagen(CTX-1),tartrate-resistant acid phosphatase 5 b(TRAP-5 b),interleukin 6(IL-6)in serum.In conclusion,tectochrysin serves as a potential candidate in the treatment of osteoporosis.The proposed twodimensional MPTS-mod

关 键 词：3-Mercaptopropyltrimethoxysilane-modifiedsilica Two-dimensional cell membrane chromatography Scutellariae Radix ANTI-OSTEOPOROSIS Tectochrysin 

分 类 号：R580[医药卫生—内分泌]