Background: Cancer poses a serious threat to human health and survival, and studies had been reported that imidazole or pyridine analogs play as an anti-cancer agent in cancer treatment. Meanwhile, Autophagy plays a d...Background: Cancer poses a serious threat to human health and survival, and studies had been reported that imidazole or pyridine analogs play as an anti-cancer agent in cancer treatment. Meanwhile, Autophagy plays a dual and substantial role in maintaining cellular homeostasis in cancers, for it is either initiated to rescue cancer cells under stress or executed to promote autophagy cell death under certain circumstances. Objective: TIP-6 was designed and synthesized (7-(4-methoxyphenyl)-5,8α-diphenyl-1,2,3,7,8, 8α-hexahyd-roimidazo[1,2-α]pyridine-6) for evaluation of its biological effects on HepG2 cells and exploring the potential anti-cancer effect. Methods and Results: Chemical synthesis results indicated that the expected compound was obtained. The results of the MTT assay showed that TIP-6 arrested the growth of HepG2 cells in G2/M phase in the cell cycle, showing significant anti-proliferation effect. And analysis of morphological changes and formation of acidic vesicular organelles showed that the autophagy was induced but not apoptosis. The results were further validated by the enhanced expression of LC3I/II, Beclin1and down-regulated expression of Bcl-2in western blot analysis. In addition, the molecular docking predicted that TIP-6 preferentially binds to Bcl-2 and Bcl-xL in the active sites. Conclusion: Overall, this study demonstrated that autophagy cell death was executed in HepG2 cells which were induced by TIP-6.展开更多
Backgrounds:Diabetes mellitus,especially type 2 diabetes,with its fast-rising prevalence,has become a global epidemic.Mulberry(Morus alba L.)leaf has been known to have hypoglycemic effects since ancient times.In Asia...Backgrounds:Diabetes mellitus,especially type 2 diabetes,with its fast-rising prevalence,has become a global epidemic.Mulberry(Morus alba L.)leaf has been known to have hypoglycemic effects since ancient times.In Asia mulberry leaf is used as tea to complement the treatment of diabetes mellitus.The methods by which mulberry leaf affects the body and its mechanism when combined with chemical agents have been studied extensively.Conclusions:We summarize the possible mechanisms of the anti-diabetic effects of mulberry leaf based on extraction procedures,in vitro and in vivo experiments,and clinical trials.We also discuss the hypothesis that crosstalk and“critical nodes”may be useful for a deeper molecular understanding of the treatment and prevention of diabetes with mulberry leaf.展开更多
Objective: To study the pharmacokinetics of puerarin(PUE) in Gegen Qinlian Decoction(葛根芩连汤, GQD), and the effects of PUE dosage variations on the pharmacokinetics of baicalin(BAL) in mice. Methods: GQD is...Objective: To study the pharmacokinetics of puerarin(PUE) in Gegen Qinlian Decoction(葛根芩连汤, GQD), and the effects of PUE dosage variations on the pharmacokinetics of baicalin(BAL) in mice. Methods: GQD is composed of the concentrated granules of four Chinese herbs. Three dosages with different levels of PUE, including GQD, GQD co-administered with PUE, and GQD co-administration with two times the amount of PUE, were used to research the pharmacokinetics of PUE and BAL in mice. The indirect competitive enzyme-linked immunosorbent assay(ic ELISA) methods based on an anti PUE-monoclonal antibody(MAb) and BAL-MAb were employed to determine the concentration of PUE and BAL in mice blood. Results: After the co-administration of GQD with PUE, the area under the curves(AUC0-14 h) of PUE increased 2.8 times compared with GQD. At the dose of GQD co-administration at two times that of PUE, the AUC0-14 h of PUE was almost equal to that of GQD co-administration of PUE, showing non-linear pharmacokinetics. The AUC0-48 h of BAL showed a good dose-related increase of PUE(r=0.993) in the range from 100 to 300 mg/kg, indicating that PUE dramatically affects the absorption of BAL in mice. There was no significant difference in the other pharmacokinetic parameters, such as the first time of maximum concentration(Tmax), the second Tmax, or the mean residence time. Conclusions: The ic ELISA methods were successfully applied to pharmacokinetic studies of PUE and BAL in GQD in mice. The dosage variability of PUE of the main ingredient in GQD affects its own pharmacokinetic characteristics and the absorption characteristics of BAL.展开更多
OBJECTIVE: To analyze the transdermal profile of pseudoephedrine and amygdalin in the Traditional Chinese Medicine majiepingchuan in rat skin and to reveal their interaction.METHODS: A Franz diffusion cell was used in...OBJECTIVE: To analyze the transdermal profile of pseudoephedrine and amygdalin in the Traditional Chinese Medicine majiepingchuan in rat skin and to reveal their interaction.METHODS: A Franz diffusion cell was used in vitro to evaluate the transdermal parameters of cumulative transdermal flux(Q_(tot)), cumulative transmission(T_(tot)), and mean penetration rate(Kp) of pseudoephedrine and amygdalin in majiepingchuan. Linear regression analyses of Q_(tot)over time of pseudoephedrine vs amygdalin and their ratios was adopted for correlation evaluation.RESULTS: At 1, 2, 4, 6, and 8 h, the Q_(tot),T_(tot)and Kp of pseudoephedrine showed a good correlation with that of amygdalin.CONCLUSION: There was a small difference in theratios of Q_(tot), T_(tot)and Kp between pseudoephedrine and amygdalin, and a correlation between them.展开更多
Objective: To explore the protective effects of Tibetan medicine Zuo-Mu-A Decoction(佐木阿汤, ZMAD) on the blood parameters and myocardium of high altitude polycythemia(HAPC) model rats. Methods: Forty male Wistar rat...Objective: To explore the protective effects of Tibetan medicine Zuo-Mu-A Decoction(佐木阿汤, ZMAD) on the blood parameters and myocardium of high altitude polycythemia(HAPC) model rats. Methods: Forty male Wistar rats were randomly divided into 4 groups by a random number table, including the normal, model, Rhodiola rosea L.(RRL) and ZMAD groups(10 in each group). Every group was raised in Lhasa to create a HAPC model except the normal group. After modeling, rats in the RRL and the ZMAD groups were administered intragastrically with RRL(20 mL/kg) and ZMAD(7.5 mL/kg) once a day for 2 months, respectively; for the normal and the model groups, 5 mL of distilled water was administered intragastrically instead of decoction. Then routine blood and hematologic rheology parameters were taken, levels of erythropoietin and 8-hydroxy-2’-deoxyguanosine(8-OHd G) were tested, and ultrastructural change in the left ventricular myocardium was observed using transmission electron microscopy. Results: Compared with the model group, ZMAD significantly reduced the red blood cell count, hemoglobin levels, whole blood viscosity at low/middle shear rates, plasma viscosity, erythrocyte electrophoretic time, erythropoietin and 8-OHd G levels, and also increased the erythrocyte deformation index(P<0.05). There was no difference in all results between the RRL and the ZMAD groups. The cardiac muscle fibers were well-protected, mitochondrial matrix swelled mildly and ultrastructure changes were less prominent in the ZMAD group compared with the model group. Conclusion: ZMAD has significant protective effects on the blood parameters against HAPC, and also has the beneficial effect in protecting against myocardial injury.展开更多
OBJECTIVE: To review the interactions between herbs and widely used drugs and summarize the associated experimental methods.METHODS: Definite herb-drug interactions were obtained by searching Pub Med, other large over...OBJECTIVE: To review the interactions between herbs and widely used drugs and summarize the associated experimental methods.METHODS: Definite herb-drug interactions were obtained by searching Pub Med, other large overseas databases and summarizing new researches from China. We summarize some methods to assess the interaction between herbs and drugs involving microsomal, cell culture and animal experiments, and clinical trials, classifying this method as single ingredient herbs, crude herb extracts, andherbal formulae.RESULTS: Many herbs interact with drugs through a complex cytochrome P450 and/or P-glycoprotein mechanism. Herb-induced enzyme inhibition and/or induction may result in enhanced and / or decreased plasma, tissue, urine and bile drug concentrations, leading to a change in a drug's pharmacokinetic parameters and resulting in the improper treatment of patients and potentially severe side effects. Use of an appropriate method for comprehensively assessing herb-drug interactions can minimize clinical risks. Different methods were used by researchers to assess the pharmacological changes of drugs in vivo and in vitro and the mechanisms of the interactions from microsomal, cell culture and animal experiments, and clinical trials are discussed in this review.CONCLUSION: Co-medication with herbs can result in changes in pharmacological effects of many drugs. This review describes the assessment of single-ingredient herbs, crude herb extracts, and herbal formulae. When choosing a research method to investigate herb-drug interactions, the properties of the drugs and herbs should be considered.展开更多
文摘Background: Cancer poses a serious threat to human health and survival, and studies had been reported that imidazole or pyridine analogs play as an anti-cancer agent in cancer treatment. Meanwhile, Autophagy plays a dual and substantial role in maintaining cellular homeostasis in cancers, for it is either initiated to rescue cancer cells under stress or executed to promote autophagy cell death under certain circumstances. Objective: TIP-6 was designed and synthesized (7-(4-methoxyphenyl)-5,8α-diphenyl-1,2,3,7,8, 8α-hexahyd-roimidazo[1,2-α]pyridine-6) for evaluation of its biological effects on HepG2 cells and exploring the potential anti-cancer effect. Methods and Results: Chemical synthesis results indicated that the expected compound was obtained. The results of the MTT assay showed that TIP-6 arrested the growth of HepG2 cells in G2/M phase in the cell cycle, showing significant anti-proliferation effect. And analysis of morphological changes and formation of acidic vesicular organelles showed that the autophagy was induced but not apoptosis. The results were further validated by the enhanced expression of LC3I/II, Beclin1and down-regulated expression of Bcl-2in western blot analysis. In addition, the molecular docking predicted that TIP-6 preferentially binds to Bcl-2 and Bcl-xL in the active sites. Conclusion: Overall, this study demonstrated that autophagy cell death was executed in HepG2 cells which were induced by TIP-6.
基金This work was carried out with the support of National Natural Science Foundation(No.81374027),the People’s Republic of China.
文摘Backgrounds:Diabetes mellitus,especially type 2 diabetes,with its fast-rising prevalence,has become a global epidemic.Mulberry(Morus alba L.)leaf has been known to have hypoglycemic effects since ancient times.In Asia mulberry leaf is used as tea to complement the treatment of diabetes mellitus.The methods by which mulberry leaf affects the body and its mechanism when combined with chemical agents have been studied extensively.Conclusions:We summarize the possible mechanisms of the anti-diabetic effects of mulberry leaf based on extraction procedures,in vitro and in vivo experiments,and clinical trials.We also discuss the hypothesis that crosstalk and“critical nodes”may be useful for a deeper molecular understanding of the treatment and prevention of diabetes with mulberry leaf.
基金supported by the Research Platform for Quality Standard of TCMs and Information System Building(No.2009ZX09308-004)National S&T Major Project-Created Major New Drugs Projects(No.2010ZX09502-002)~~
基金Supported by the National Natural Science Foundation of China(No.81274043)
文摘Objective: To study the pharmacokinetics of puerarin(PUE) in Gegen Qinlian Decoction(葛根芩连汤, GQD), and the effects of PUE dosage variations on the pharmacokinetics of baicalin(BAL) in mice. Methods: GQD is composed of the concentrated granules of four Chinese herbs. Three dosages with different levels of PUE, including GQD, GQD co-administered with PUE, and GQD co-administration with two times the amount of PUE, were used to research the pharmacokinetics of PUE and BAL in mice. The indirect competitive enzyme-linked immunosorbent assay(ic ELISA) methods based on an anti PUE-monoclonal antibody(MAb) and BAL-MAb were employed to determine the concentration of PUE and BAL in mice blood. Results: After the co-administration of GQD with PUE, the area under the curves(AUC0-14 h) of PUE increased 2.8 times compared with GQD. At the dose of GQD co-administration at two times that of PUE, the AUC0-14 h of PUE was almost equal to that of GQD co-administration of PUE, showing non-linear pharmacokinetics. The AUC0-48 h of BAL showed a good dose-related increase of PUE(r=0.993) in the range from 100 to 300 mg/kg, indicating that PUE dramatically affects the absorption of BAL in mice. There was no significant difference in the other pharmacokinetic parameters, such as the first time of maximum concentration(Tmax), the second Tmax, or the mean residence time. Conclusions: The ic ELISA methods were successfully applied to pharmacokinetic studies of PUE and BAL in GQD in mice. The dosage variability of PUE of the main ingredient in GQD affects its own pharmacokinetic characteristics and the absorption characteristics of BAL.
基金Supported by the Science and Technology Major Projects for Major New Drugs(Research on innovation of Majiepingchuan effective components cataplasm of transdermal drug delivery system),No.2012ZX09103201-007
文摘OBJECTIVE: To analyze the transdermal profile of pseudoephedrine and amygdalin in the Traditional Chinese Medicine majiepingchuan in rat skin and to reveal their interaction.METHODS: A Franz diffusion cell was used in vitro to evaluate the transdermal parameters of cumulative transdermal flux(Q_(tot)), cumulative transmission(T_(tot)), and mean penetration rate(Kp) of pseudoephedrine and amygdalin in majiepingchuan. Linear regression analyses of Q_(tot)over time of pseudoephedrine vs amygdalin and their ratios was adopted for correlation evaluation.RESULTS: At 1, 2, 4, 6, and 8 h, the Q_(tot),T_(tot)and Kp of pseudoephedrine showed a good correlation with that of amygdalin.CONCLUSION: There was a small difference in theratios of Q_(tot), T_(tot)and Kp between pseudoephedrine and amygdalin, and a correlation between them.
基金Supported by the National Natural Science Foundation of China(No.81260567)
文摘Objective: To explore the protective effects of Tibetan medicine Zuo-Mu-A Decoction(佐木阿汤, ZMAD) on the blood parameters and myocardium of high altitude polycythemia(HAPC) model rats. Methods: Forty male Wistar rats were randomly divided into 4 groups by a random number table, including the normal, model, Rhodiola rosea L.(RRL) and ZMAD groups(10 in each group). Every group was raised in Lhasa to create a HAPC model except the normal group. After modeling, rats in the RRL and the ZMAD groups were administered intragastrically with RRL(20 mL/kg) and ZMAD(7.5 mL/kg) once a day for 2 months, respectively; for the normal and the model groups, 5 mL of distilled water was administered intragastrically instead of decoction. Then routine blood and hematologic rheology parameters were taken, levels of erythropoietin and 8-hydroxy-2’-deoxyguanosine(8-OHd G) were tested, and ultrastructural change in the left ventricular myocardium was observed using transmission electron microscopy. Results: Compared with the model group, ZMAD significantly reduced the red blood cell count, hemoglobin levels, whole blood viscosity at low/middle shear rates, plasma viscosity, erythrocyte electrophoretic time, erythropoietin and 8-OHd G levels, and also increased the erythrocyte deformation index(P<0.05). There was no difference in all results between the RRL and the ZMAD groups. The cardiac muscle fibers were well-protected, mitochondrial matrix swelled mildly and ultrastructure changes were less prominent in the ZMAD group compared with the model group. Conclusion: ZMAD has significant protective effects on the blood parameters against HAPC, and also has the beneficial effect in protecting against myocardial injury.
基金National Natural Science Foundation of China(Research Method and Key Technology of Intracorporal Process of Therapeutic Material Basis Based on Concurrent Multiple Metabolism,No.81274042)Special Fund for Scientific Research in the Public Interest(Research on the Treament of Cerebral Infarction With the Combination of Chinese and Western Medicine and the Literature Analysis,No.201407013)
文摘OBJECTIVE: To review the interactions between herbs and widely used drugs and summarize the associated experimental methods.METHODS: Definite herb-drug interactions were obtained by searching Pub Med, other large overseas databases and summarizing new researches from China. We summarize some methods to assess the interaction between herbs and drugs involving microsomal, cell culture and animal experiments, and clinical trials, classifying this method as single ingredient herbs, crude herb extracts, andherbal formulae.RESULTS: Many herbs interact with drugs through a complex cytochrome P450 and/or P-glycoprotein mechanism. Herb-induced enzyme inhibition and/or induction may result in enhanced and / or decreased plasma, tissue, urine and bile drug concentrations, leading to a change in a drug's pharmacokinetic parameters and resulting in the improper treatment of patients and potentially severe side effects. Use of an appropriate method for comprehensively assessing herb-drug interactions can minimize clinical risks. Different methods were used by researchers to assess the pharmacological changes of drugs in vivo and in vitro and the mechanisms of the interactions from microsomal, cell culture and animal experiments, and clinical trials are discussed in this review.CONCLUSION: Co-medication with herbs can result in changes in pharmacological effects of many drugs. This review describes the assessment of single-ingredient herbs, crude herb extracts, and herbal formulae. When choosing a research method to investigate herb-drug interactions, the properties of the drugs and herbs should be considered.