Osteoporosis(OP)is a debilitating skeletal abnormality involving bone remodeling and bone cell homeostasis characterized by decreased bone strength and high fracture risk.A novel therapeutic intervention for OP by man...Osteoporosis(OP)is a debilitating skeletal abnormality involving bone remodeling and bone cell homeostasis characterized by decreased bone strength and high fracture risk.A novel therapeutic intervention for OP by manipulating cellular autophagy-apoptosis processes to promote skeletal homeostasis is presented.Protective effects of the naturally occurring plant extract Liquiritigenin(LG)were demonstrated in an ovariectomy(OvX)-OP mouse model and preosteoblast MC3T3-E1 cells.Micro-CT and histological staining assessments of skeletal phenotype were applied alongside detection of autophagy activity in osteocytes and MC3T3-E1 cells by transmission electron microscopy(TEM).The effects of LG on chloroquine(CQ)-and the apoptosis-inducing TS-treated osteogenic differentiations and status of lysosomes within MC3T3-E1 cells were analyzed by Neutral red,Alizarin red S and alkaline phosphatase(ALP)staining and Western blot assays.Treatment with LG prevented bone loss,increased osteogenic differentiation in vivo and in vitro,and inhibited osteoclast formation to some extent.TEM analyses revealed that LG can improve auto-lysosomal degradation within osteocytes from OVX mice and MC3T3-E1 cells.The abnormal status of lysosomes associated with CQ and TS treatments was notably alleviated by LG which also reduced levels of apoptosis-induced inhibition of osteogenic differentiation and averted abnormal osteogenic differentiation as a consequence of a blockage in autolysosome degradation.Overall,LG stimulates bone growth in Oovx mice through increased osteogenic differentiation and regulation of autophagyapoptosis mechanisms,presenting an auspicious natural therapy for Op.展开更多
In the present study,liquiritigenin-phospholipid complex(LPC)was developed and evaluated to increase the oral bioavailability of liquiritigenin.A single-factor test methodology was applied to optimize the formulation ...In the present study,liquiritigenin-phospholipid complex(LPC)was developed and evaluated to increase the oral bioavailability of liquiritigenin.A single-factor test methodology was applied to optimize the formulation and process for preparing LPC.The effects of solvent,drug concentration,reaction time,temperature and drug-to-phospholipid ratio on encapsulation efficiency were investigated.LPCs were characterized by UV-visible spectroscopy,differential scanning calorimetry(DSC),fourier transform infrared spectroscopy(FTIR),and powder X-ray diffractometry(PXRD).The apparent solubility and n-octanol/water partition coefficient were tested.The pharmacokinetic characteristics and bioavailability of the LPC were investigated after oral administration in rats in comparison with liquiritigenin alone.An LPC was successfully prepared.The optimum level of various parameters for liquiritigeninphospholipid complex was obtained at the drug concentration of 8 mg·mL-1,reaction time for 15 min,reaction temperature of 30℃,a ratio of 1∶4.5(W/W)drug-to-phospholipid and anhydrous ethanol as reaction solvent.Compared to liquiritigenin,the AUC0-t of the LPC was increased by 239%.The liquiritigenin-phospholipid complex significantly increase the lipid solubility and bioavailability of liquiritigenin,suggesting that it is an effective formulation for further development and clinical applications.展开更多
A monolithic polymer column with mixed-mode interaction was prepared by in situ polymerization in a 1000μL pipette. Two kinds of monomers, butyl methacrylate （BMA） and 2-（dimethylamino）ethyl methacrylate （DMAM）...A monolithic polymer column with mixed-mode interaction was prepared by in situ polymerization in a 1000μL pipette. Two kinds of monomers, butyl methacrylate （BMA） and 2-（dimethylamino）ethyl methacrylate （DMAM） were applied to constructing the mixed-mode interaction of monolithic polymer column. Its solid-phase extraction properties for liquiritigenin （LQG） were evaluated by high performance liquid chromatography （HPLC） with a gradient elution procedure. After the extraction procedure was optimized, the maximum binding capacity and extraction recovery following the optimal extraction procedure were investigated. Calibration curve was expressed as A = 65.9C ＋ 4.53 （r2 = 0.998） with a linear range of 0.151-1.80μg/mL. The experimental results indicate that the monolithic polymer pipette presents good extraction efficiency for LQG. It can be envisaged that the developed monolithic polymer pipette possesses the potential for its application to the enrichment of other flavonoids compounds being similar to the structure of LQG.展开更多
Objective A simple, sensitive, and rapid LC-MS/MS method has been established and validated for the determination of liquiritigenin （LG） in rat plasma. Methods Naringenin was chosen as internal standard （IS）. LG a...Objective A simple, sensitive, and rapid LC-MS/MS method has been established and validated for the determination of liquiritigenin （LG） in rat plasma. Methods Naringenin was chosen as internal standard （IS）. LG and IS were separated on a Diamonsil C18 analytical column with a mobile phase of methanol-10% methanol in water containing 0.5 mmol/L ammonium formate and 0.2% formic acid （55：45） at the isocratic flow rate of 0.6 mL/min for 10 min. The multiple reaction monitoring （MRM） was performed on a mass spectrometer in the negative ion mode with electro-spray ionization （ESI） source and the transition from precursor ion to product ion was m/z255.0~119.0 for LG and m/z 271.04151.0 for IS, respectively. Results The linearity was acceptable in the range of 5-5000 ng/mL （r= 0.9973）. The inter-day and intra-day accuracies were in the ranges of -0.09%-3.25% and -5.02%-9.21%, respectively. The precision was in the ranges of 3.60%-12.4% and 0.909%-6.89%, respectively. LG was stable in the course of anarysis and storage. Conclusion The LC-MS/MS method was successfully applied to the pharmacokinetic study for the first time in rats after ig and iv administration of liquiritin （LQ）, a glycoside of LG, at pharmacologically effective levels.展开更多
基金This study was supported by the National Natural Science Foundation of China(No.81671257,81371221,31600825)81671257,81371221,31600825)Innovation Research Group at Institutions of Higher Education in Chongqing,China(No.CXQTP19019019034)Program for Innovation Team Building at Institutions of Higher Education in Chongqing in 2016.
文摘Osteoporosis(OP)is a debilitating skeletal abnormality involving bone remodeling and bone cell homeostasis characterized by decreased bone strength and high fracture risk.A novel therapeutic intervention for OP by manipulating cellular autophagy-apoptosis processes to promote skeletal homeostasis is presented.Protective effects of the naturally occurring plant extract Liquiritigenin(LG)were demonstrated in an ovariectomy(OvX)-OP mouse model and preosteoblast MC3T3-E1 cells.Micro-CT and histological staining assessments of skeletal phenotype were applied alongside detection of autophagy activity in osteocytes and MC3T3-E1 cells by transmission electron microscopy(TEM).The effects of LG on chloroquine(CQ)-and the apoptosis-inducing TS-treated osteogenic differentiations and status of lysosomes within MC3T3-E1 cells were analyzed by Neutral red,Alizarin red S and alkaline phosphatase(ALP)staining and Western blot assays.Treatment with LG prevented bone loss,increased osteogenic differentiation in vivo and in vitro,and inhibited osteoclast formation to some extent.TEM analyses revealed that LG can improve auto-lysosomal degradation within osteocytes from OVX mice and MC3T3-E1 cells.The abnormal status of lysosomes associated with CQ and TS treatments was notably alleviated by LG which also reduced levels of apoptosis-induced inhibition of osteogenic differentiation and averted abnormal osteogenic differentiation as a consequence of a blockage in autolysosome degradation.Overall,LG stimulates bone growth in Oovx mice through increased osteogenic differentiation and regulation of autophagyapoptosis mechanisms,presenting an auspicious natural therapy for Op.
文摘In the present study,liquiritigenin-phospholipid complex(LPC)was developed and evaluated to increase the oral bioavailability of liquiritigenin.A single-factor test methodology was applied to optimize the formulation and process for preparing LPC.The effects of solvent,drug concentration,reaction time,temperature and drug-to-phospholipid ratio on encapsulation efficiency were investigated.LPCs were characterized by UV-visible spectroscopy,differential scanning calorimetry(DSC),fourier transform infrared spectroscopy(FTIR),and powder X-ray diffractometry(PXRD).The apparent solubility and n-octanol/water partition coefficient were tested.The pharmacokinetic characteristics and bioavailability of the LPC were investigated after oral administration in rats in comparison with liquiritigenin alone.An LPC was successfully prepared.The optimum level of various parameters for liquiritigeninphospholipid complex was obtained at the drug concentration of 8 mg·mL-1,reaction time for 15 min,reaction temperature of 30℃,a ratio of 1∶4.5(W/W)drug-to-phospholipid and anhydrous ethanol as reaction solvent.Compared to liquiritigenin,the AUC0-t of the LPC was increased by 239%.The liquiritigenin-phospholipid complex significantly increase the lipid solubility and bioavailability of liquiritigenin,suggesting that it is an effective formulation for further development and clinical applications.
基金supports of the National Natural Science Foundation of China (No.30801515)the Scientific Research Foundation for the Returned Overseas Chinese Scholars,State Education Ministry(No.[2011]1139)the Open Fund of Key Laboratory of Analytical Chemistry for Living Biosystems, CAS(No.ACL201202)
文摘A monolithic polymer column with mixed-mode interaction was prepared by in situ polymerization in a 1000μL pipette. Two kinds of monomers, butyl methacrylate （BMA） and 2-（dimethylamino）ethyl methacrylate （DMAM） were applied to constructing the mixed-mode interaction of monolithic polymer column. Its solid-phase extraction properties for liquiritigenin （LQG） were evaluated by high performance liquid chromatography （HPLC） with a gradient elution procedure. After the extraction procedure was optimized, the maximum binding capacity and extraction recovery following the optimal extraction procedure were investigated. Calibration curve was expressed as A = 65.9C ＋ 4.53 （r2 = 0.998） with a linear range of 0.151-1.80μg/mL. The experimental results indicate that the monolithic polymer pipette presents good extraction efficiency for LQG. It can be envisaged that the developed monolithic polymer pipette possesses the potential for its application to the enrichment of other flavonoids compounds being similar to the structure of LQG.
基金"Twelfth Five-year Plan"-Major Technological Projects of "Creation of Major New Drug"(2012ZX09506-001)National 973 Program of China(2010CB933900)Tianjin Science and Technology Plan Project(10SYSYJC28600)
文摘Objective A simple, sensitive, and rapid LC-MS/MS method has been established and validated for the determination of liquiritigenin （LG） in rat plasma. Methods Naringenin was chosen as internal standard （IS）. LG and IS were separated on a Diamonsil C18 analytical column with a mobile phase of methanol-10% methanol in water containing 0.5 mmol/L ammonium formate and 0.2% formic acid （55：45） at the isocratic flow rate of 0.6 mL/min for 10 min. The multiple reaction monitoring （MRM） was performed on a mass spectrometer in the negative ion mode with electro-spray ionization （ESI） source and the transition from precursor ion to product ion was m/z255.0~119.0 for LG and m/z 271.04151.0 for IS, respectively. Results The linearity was acceptable in the range of 5-5000 ng/mL （r= 0.9973）. The inter-day and intra-day accuracies were in the ranges of -0.09%-3.25% and -5.02%-9.21%, respectively. The precision was in the ranges of 3.60%-12.4% and 0.909%-6.89%, respectively. LG was stable in the course of anarysis and storage. Conclusion The LC-MS/MS method was successfully applied to the pharmacokinetic study for the first time in rats after ig and iv administration of liquiritin （LQ）, a glycoside of LG, at pharmacologically effective levels.
