Chrysin(1) and tectochrysin(2) were respectively synthesized in four steps from 1,3,5-tribromobenzene in an overall yield of 46.8% and that of 37.0% with the key step being the Bu_4NBr catalyzed hydrolysis of 1-phenyl...Chrysin(1) and tectochrysin(2) were respectively synthesized in four steps from 1,3,5-tribromobenzene in an overall yield of 46.8% and that of 37.0% with the key step being the Bu_4NBr catalyzed hydrolysis of 1-phenyl-3-(2′,4′,6′-trimethoxyphenyl)-1, 3-propanedione (11) under different conditions.展开更多
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 sh...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-modified BMMC/CMC-TOFMS analytical system shows the advantages of longlife span and fast recognition ability,which is very suitable for infrequent cell lines.展开更多
文摘Chrysin(1) and tectochrysin(2) were respectively synthesized in four steps from 1,3,5-tribromobenzene in an overall yield of 46.8% and that of 37.0% with the key step being the Bu_4NBr catalyzed hydrolysis of 1-phenyl-3-(2′,4′,6′-trimethoxyphenyl)-1, 3-propanedione (11) under different conditions.
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)
文摘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-modified BMMC/CMC-TOFMS analytical system shows the advantages of longlife span and fast recognition ability,which is very suitable for infrequent cell lines.
