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 antiosteoporosis activity through inhibiting the differentiation from bone marrow mononuclear cells (BMMCs) to osteoclast were screened by a BMMC/CMC analytical system.Firstly,a new 3-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 5b (TRAP-5b),interleukin 6 (IL-6) in serum.In conclusion,tectochrysin serves as a potential candidate in the treatment of osteoporosis.The proposed twodimensional MPTS-modified BMMC/CMC-TOFMS analytical system shows the advantages of longlife span and fast recognition ability,which is very suitable for infrequent cell lines.