AIM: To investigate the absorption characteristics of the total alkaloids from Mahoniae Caulis(TAMC) through the administration of monterpene absorption enhancers or protein inhibitors. METHOD: The absorption behavior...AIM: To investigate the absorption characteristics of the total alkaloids from Mahoniae Caulis(TAMC) through the administration of monterpene absorption enhancers or protein inhibitors. METHOD: The absorption behavior was investigated in an in situ single-pass intestinal perfusion(SPIP) assay in rats. RESULTS: The intestinal absorption of TAMC was much more than that of a single compound or a mixture of compounds(jatrorrhizine, palmatine, and berberine). Promotion of absorption by the bicyclic monoterpenoids(borneol or camphor) was higher than by the monocyclic monoterpenes(menthol or menthone), and promotion by compounds with a hydroxyl group(borneol or menthol) was higher than those with a carbonyl group(camphor or menthone). The apparent permeability coefficient(Papp) of TAMC was increased to 1.8-fold by verapamil, while it was reduced to one half by thiamine. The absorption rate constant(Ka) and Papp of TAMC were unchanged by probenecid and pantoprazole. CONCLUSION: The intestinal absorption characteristics of TAMC might be passive transport, and the intestinum tenue was the best absorptive site. In addition, TAMC might be likely a substrate of P-glycoprotein(P-gp) and organic cation transporters(OCT), rather than multidrug resistance protein(MRP) and breast cancer resistance protein(BCRP). Compared with a single compound and a mixture of compounds, TAMC was able to be absorbed in the blood circulation effectively.展开更多
Biocontrol strain Pseudomonas PA1201 produces pyoluteorin(Plt),which is an antimicrobial secondary metabolite.Plt represents a promising candidate pesticide due to its broad-spectrum antifungal and antibacterial activ...Biocontrol strain Pseudomonas PA1201 produces pyoluteorin(Plt),which is an antimicrobial secondary metabolite.Plt represents a promising candidate pesticide due to its broad-spectrum antifungal and antibacterial activity.Although PA1201 contains a complete genetic cluster for Plt biosynthesis,it fails to produce detectable level of Plt when grown in media typically used for Pseudomonas strains.In this study,minimum medium(MM)was found to favor Plt biosynthesis.Using the medium M,which contains all the salts of MM medium except for mannitol,as a basal medium,we compared 10 carbon sources for their ability to promote Plt biosynthesis.Fructose,mannitol,and glycerol promoted Plt biosynthesis,with fructose being the most effective carbon source.Glucose or succinic acid had no significant effect on Plt biosynthesis,but effectively antagonized fructose-dependent synthesis of Plt.Promoter-lacZ fusion reporter strains demonstrated that fructose acted through activation of the pltLABCDEFG(pltL)operon but had no effect on other genes of plt gene cluster;glucose or succinic acid antagonized fructose-dependent pltL induction.Mechanistically,fructose-mediated Plt synthesis involved carbon catabolism repression.The two-component system CbrA/CbrB and small RNA catabolite repression control Z(crcZ)were essential for fructose-induced Plt synthesis.The small RNA binding protein Hfq and Crc negatively regulated fructose-induced Plt.Taken together,this study provides a new model of fructose-dependent Plt production in PA1201 that can help improve Plt yield by biosynthetic approaches.展开更多
基金supported by China Pharmaceutical University Training Programs of Innovation for Undergraduates(No.02640390)
文摘AIM: To investigate the absorption characteristics of the total alkaloids from Mahoniae Caulis(TAMC) through the administration of monterpene absorption enhancers or protein inhibitors. METHOD: The absorption behavior was investigated in an in situ single-pass intestinal perfusion(SPIP) assay in rats. RESULTS: The intestinal absorption of TAMC was much more than that of a single compound or a mixture of compounds(jatrorrhizine, palmatine, and berberine). Promotion of absorption by the bicyclic monoterpenoids(borneol or camphor) was higher than by the monocyclic monoterpenes(menthol or menthone), and promotion by compounds with a hydroxyl group(borneol or menthol) was higher than those with a carbonyl group(camphor or menthone). The apparent permeability coefficient(Papp) of TAMC was increased to 1.8-fold by verapamil, while it was reduced to one half by thiamine. The absorption rate constant(Ka) and Papp of TAMC were unchanged by probenecid and pantoprazole. CONCLUSION: The intestinal absorption characteristics of TAMC might be passive transport, and the intestinum tenue was the best absorptive site. In addition, TAMC might be likely a substrate of P-glycoprotein(P-gp) and organic cation transporters(OCT), rather than multidrug resistance protein(MRP) and breast cancer resistance protein(BCRP). Compared with a single compound and a mixture of compounds, TAMC was able to be absorbed in the blood circulation effectively.
文摘Biocontrol strain Pseudomonas PA1201 produces pyoluteorin(Plt),which is an antimicrobial secondary metabolite.Plt represents a promising candidate pesticide due to its broad-spectrum antifungal and antibacterial activity.Although PA1201 contains a complete genetic cluster for Plt biosynthesis,it fails to produce detectable level of Plt when grown in media typically used for Pseudomonas strains.In this study,minimum medium(MM)was found to favor Plt biosynthesis.Using the medium M,which contains all the salts of MM medium except for mannitol,as a basal medium,we compared 10 carbon sources for their ability to promote Plt biosynthesis.Fructose,mannitol,and glycerol promoted Plt biosynthesis,with fructose being the most effective carbon source.Glucose or succinic acid had no significant effect on Plt biosynthesis,but effectively antagonized fructose-dependent synthesis of Plt.Promoter-lacZ fusion reporter strains demonstrated that fructose acted through activation of the pltLABCDEFG(pltL)operon but had no effect on other genes of plt gene cluster;glucose or succinic acid antagonized fructose-dependent pltL induction.Mechanistically,fructose-mediated Plt synthesis involved carbon catabolism repression.The two-component system CbrA/CbrB and small RNA catabolite repression control Z(crcZ)were essential for fructose-induced Plt synthesis.The small RNA binding protein Hfq and Crc negatively regulated fructose-induced Plt.Taken together,this study provides a new model of fructose-dependent Plt production in PA1201 that can help improve Plt yield by biosynthetic approaches.
