Induction of Phase I, II and III Drug Metabolism/Transport by Xenobiotics

Changjiang Xu,Christina Yong-Tao Li,Ah-Ng Tony Kong 대한약학회 2005 Archives of Pharmacal Research Vol.28 No.3

Nonlinear aerodynamic stability analysis of orthotropic membrane structures with large amplitude

Zheng, Zhoulian,Xu, Yunping,Liu, Changjiang,He, Xiaoting,Song, Weiju Techno-Press 2011 Structural Engineering and Mechanics, An Int'l Jou Vol.37 No.4

The aerodynamic stability of orthotropic tensioned membrane structures with rectangular plane is theoretically studied under the uniform ideal potential flow. The aerodynamic force acting on the membrane surface is determined by the potential flow theory in fluid mechanics and the thin airfoil theory in aerodynamics. Then, based on the large amplitude theory and the D'Alembert's principle, the interaction governing equation of wind-structure is established. Under the circumstances of single mode response, the Bubnov-Galerkin approximate method is applied to transform the complicated interaction equation into a system of second order nonlinear differential equation with constant coefficients. Through judging the stability of the system characteristic equation, the critical divergence instability wind velocity is determined. Finally, from different parametric analysis, we can conclude that it has positive significance to consider the characteristics of orthotropic and large amplitude for preventing the instability destruction of structures.

A NOTE ON LINEAR COMBINATIONS OF AN IDEMPOTENT MATRIX AND A TRIPOTENT MATRIX

Yao, Hongmei,Sun, Yanling,Xu, Chuang,Bu, Changjiang The Korean Society for Computational and Applied M 2009 Journal of applied mathematics & informatics Vol.27 No.5

Let $A_1$ and $A_2$ be nonzero complex idempotent and tripotent matrix, respectively. Denote a linear combination of the two matrices by A = $c_1A_1$ + $c_2A_2$, where $c_1,\;c_2$ are nonzero complex scalars. In this paper, under an assumption of $A_1A_2$ = $A_2A_1$, we characterize all situations in which the linear combination is tripotent. A statistical interpretation of this tripotent problem is also pointed out. Moreover, In [2], Baksalary characterized all situations in which the above linear combination is idem-potent by using the property of decomposition of a tripotent matrix, i.e. if $A_2$ is tripotent, then $A_2$ = $B_1-B_2$, where $B^2_i=B_i$, i = 1, 2 and $B_1B_2=B_2B_1=0$. While in this paper, by utilizing a method different from the one used by Baksalary in [2], we prove the theorem 1 in [2] again.

Nonlinear aerodynamic stability analysis of orthotropic membrane structures with large amplitude

Zhoulian Zheng,Yunping Xu,Changjiang Liu,Xiaoting He,Weiju Song 국제구조공학회 2011 Structural Engineering and Mechanics, An Int'l Jou Vol.37 No.4

The aerodynamic stability of orthotropic tensioned membrane structures with rectangular plane is theoretically studied under the uniform ideal potential flow. The aerodynamic force acting on the membrane surface is determined by the potential flow theory in fluid mechanics and the thin airfoil theory in aerodynamics. Then, based on the large amplitude theory and the D'Alembert's principle, the interaction governing equation of wind-structure is established. Under the circumstances of single mode response, the Bubnov-Galerkin approximate method is applied to transform the complicated interaction equation into a system of second order nonlinear differential equation with constant coefficients. Through judging the stability of the system characteristic equation, the critical divergence instability wind velocity is determined. Finally, from different parametric analysis, we can conclude that it has positive significance to consider the characteristics of orthotropic and large amplitude for preventing the instability destruction of structures.

A note on linear combinations of an idempotent matrix and a tripotent matrix

Hongmei Yao,Yanling Sun,CHUANG XU,CHANGJIANG BU 한국전산응용수학회 2009 Journal of applied mathematics & informatics Vol.27 No.5

Let A1 and A2 be nonzero complex idempotent and tripotent matrix, respectively. Denote a linear combination of the two matrices by A = c1A1 + c2A2, where c1, c2 are nonzero complex scalars. In this paper, under an assumption of A1A2 = A2A1, we characterize all situations in which the linear combination is tripotent. A statistical interpretation of this tripotent problem is also pointed out. Moreover, In [2], Baksalary characterized all situations in which the above linear combination is idempotent by using the property of decomposition of a tripotent matrix, i.e. if A2 is tripotent, then A2 = B1 −B2, where B2 i = Bi, i = 1, 2 and B1B2 = B2B1 = 0. While in this paper, by utilizing a method different from the one used by Baksalary in [2], we prove the theorem 1 in [2] again. Let A1 and A2 be nonzero complex idempotent and tripotent matrix, respectively. Denote a linear combination of the two matrices by A = c1A1 + c2A2, where c1, c2 are nonzero complex scalars. In this paper, under an assumption of A1A2 = A2A1, we characterize all situations in which the linear combination is tripotent. A statistical interpretation of this tripotent problem is also pointed out. Moreover, In [2], Baksalary characterized all situations in which the above linear combination is idempotent by using the property of decomposition of a tripotent matrix, i.e. if A2 is tripotent, then A2 = B1 −B2, where B2 i = Bi, i = 1, 2 and B1B2 = B2B1 = 0. While in this paper, by utilizing a method different from the one used by Baksalary in [2], we prove the theorem 1 in [2] again.

Tentative identification of 20(S)-protopanaxadiol metabolites in human plasma and urine using ultra-performance liquid chromatography coupled with triple quadrupole time-of-flight mass spectrometry

Jin Ling,Yingjia Yu,Jiakun Long,Yan Li,Jiebing Jiang,Liping Wang,Changjiang Xu,Gengli Duan 고려인삼학회 2019 Journal of Ginseng Research Vol.43 No.4

Background: 20(S)-Protopanaxadiol (PPD), the aglycone part of 20(S)-protopanaxadiol ginsenosides,possesses antidepressant activity among many other pharmacological activities. It is currently undergoingclinical trial in China as an antidepressant. Methods: In this study, an ultra-performance liquid chromatography coupled with triple quadrupoletime-of-flight mass tandem mass spectrometry method was established to identify the metabolites ofPPD in human plasma and urine following oral administration in phase IIa clinical trial. Results: A total of 40 metabolites in human plasma and urine were identified using this method. Fourmetabolites identified were isolated from rat feces, and two of them were analyzed by NMR to elucidatethe exact structures. The structures of isolated compounds were confirmed as (20S,24S)-epoxydammarane-12,23,25-triol-3-one and (20S,24S)-epoxydammarane-3,12,23,25-tetrol. Both compoundswere found as metabolites in human for the first time. Upon comparing our findings with the findings ofthe in vitro study of PPD metabolism in human liver microsomes and human hepatocytes, metaboliteswith m/z 475.3783 and phase II metabolites were not found in our study whereas metabolites with m/z505.3530, 523.3641, and 525.3788 were exclusively detected in our experiments. Conclusion: The metabolites identified using ultra-performance liquid chromatography coupled withtriple quadrupole time-of-flight mass spectrometry in our study were mostly hydroxylated metabolites. This indicated that PPD was metabolized in human body mainly through phase I hepatic metabolism. Themain metabolites are in 20,24-oxide form with multiple hydroxylation sites. Finally, the metabolicpathways of PPD in vivo (human) were proposed based on structural analysis.

Tentative identification of 20(S)-protopanaxadiol metabolites in human plasma and urine using ultra-performance liquid chromatography coupled with triple quadrupole time-of-flight mass spectrometry

Ling, Jin,Yu, Yingjia,Long, Jiakun,Li, Yan,Jiang, Jiebing,Wang, Liping,Xu, Changjiang,Duan, Gengli The Korean Society of Ginseng 2019 Journal of Ginseng Research Vol.43 No.4

Background: 20(S)-Protopanaxadiol (PPD), the aglycone part of 20(S)-protopanaxadiol ginsenosides, possesses antidepressant activity among many other pharmacological activities. It is currently undergoing clinical trial in China as an antidepressant. Methods: In this study, an ultra-performance liquid chromatography coupled with triple quadrupole time-of-flight mass tandem mass spectrometry method was established to identify the metabolites of PPD in human plasma and urine following oral administration in phase IIa clinical trial. Results: A total of 40 metabolites in human plasma and urine were identified using this method. Four metabolites identified were isolated from rat feces, and two of them were analyzed by NMR to elucidate the exact structures. The structures of isolated compounds were confirmed as (20S,24S)-epoxydammarane-12,23,25-triol-3-one and (20S,24S)-epoxydammarane-3,12,23,25-tetrol. Both compounds were found as metabolites in human for the first time. Upon comparing our findings with the findings of the in vitro study of PPD metabolism in human liver microsomes and human hepatocytes, metabolites with m/z 475.3783 and phase II metabolites were not found in our study whereas metabolites with m/z 505.3530, 523.3641, and 525.3788 were exclusively detected in our experiments. Conclusion: The metabolites identified using ultra-performance liquid chromatography coupled with triple quadrupole time-of-flight mass spectrometry in our study were mostly hydroxylated metabolites. This indicated that PPD was metabolized in human body mainly through phase I hepatic metabolism. The main metabolites are in 20,24-oxide form with multiple hydroxylation sites. Finally, the metabolic pathways of PPD in vivo (human) were proposed based on structural analysis.

In vivo Pharmacokinetics, Activation of MAPK Signaling and Induction of Phase II/III Drug Metabolizing Enzymes/Transporters by Cancer Chemopreventive Compound BHA in the Mice

Hu, Rong,Shen, Guoxiang,Yerramilli, Usha Rao,Lin, Wen,Xu, Changjiang,Nair, Sujit,Kong, Ah-Ng Tony The Pharmaceutical Society of Korea 2006 Archives of Pharmacal Research Vol.29 No.10

Phenolic antioxidant butylated hydroxyanisole (BHA) is a commonly used food preservative with broad biological activities, including protection against chemical-induced carcinogenesis, acute toxicity of chemicals, modulation of macromolecule synthesis and immune response, induction of phase II detoxifying enzymes, as well as its undesirable potential tumor-promoting activities. Understanding the molecular basis underlying these diverse biological actions of BHA is thus of great importance. Here we studied the pharmacokinetics, activation of signaling kinases and induction of phase II/III drug metabolizing enzymes/transporter gene expression by BHA in the mice. The peak plasma concentration of BHA achieved in our current study after oral administration of 200 mg/kg BHA was around $10\;{\mu}M$. This in vivo concentration might offer some insights for the many in vitro cell culture studies on signal transduction and induction of phase II genes using similar concentrations. The oral bioavailability (F) of BHA was about 43% in the mice. In the mouse liver, BHA induced the expression of phase II genes including NQO-1, HO-1, ${\gamma}-GCS$, GST-pi and UGT 1A6, as well as some of the phase III transporter genes, such as MRP1 and Slco1b2. In addition, BHA activated distinct mitogen-activated protein kinases (MAPKs), c-Jun N-terminal kinase (JNK), extracellular signal-regulated protein kinase (ERK), as well as p38, suggesting that the MAPK pathways may play an important role in early signaling events leading to the regulation of gene expression including phase II drug metabolizing and some phase III drug transporter genes. This is the first study to demonstrate the in vivo pharmacokinetics of BHA, the in vivo activation of MAPK signaling proteins, as well as the in vivo induction of Phase II/III drug metabolizing enzymes/transporters in the mouse livers.

In vivo Pharmacokinetics, Activation of MAPK Signaling and Induction of Phase II/III 911Drug Metabolizing Enzymes/Transporters by Cancer Chemopreventive CompoundBHA in the Mice

Rong Hu,Guoxiang Shen,Usha Rao Yerramilli,Wen Lin,Changjiang Xu,Sujit Nair,Ah-Ng Tony Kong 대한약학회 2006 Archives of Pharmacal Research Vol.29 No.10

Phenolic antioxidant butylated hydroxyanisole (BHA) is a commonly used food preservative with broad biological activities, including protection against chemical-induced carcinogenesis, acute toxicity of chemicals, modulation of macromolecule synthesis and immune response, induction of phase II detoxifying enzymes, as well as its undesirable potential tumor-promoting activities. Understanding the molecular basis underlying these diverse biological actions of BHA is thus of great importance. Here we studied the pharmacokinetics, activation of signaling kinases and induction of phase II/III drug metabolizing enzymes/transporter gene expression by BHA in the mice. The peak plasma concentration of BHA achieved in our current study after oral administration of 200 mg/kg BHA was around 10 μM. This in vivo concentration might offer some insights for the many in vitro cell culture studies on signal transduction and induction of phase II genes using similar concentrations. The oral bioavailability (F) of BHA was about 43% in the mice. In the mouse liver, BHA induced the expression of phase II genes including NQO-1, HO-1, γ-GCS, GST-pi and UGT 1A6, as well as some of the phase III transporter genes, such as MRP1 and Slco1b2. In addition, BHA activated distinct mitogen-activated protein kinases (MAPKs), c-Jun N-terminal kinase (JNK), extracellular signal-regulated protein kinase (ERK), as well as p38, suggesting that the MAPK pathways may play an important role in early signaling events leading to the regulation of gene expression including phase II drug metabolizing and some phase III drug transporter genes. This is the first study to demonstrate the in vivo pharmacokinetics of BHA, the in vivo activation of MAPK signaling proteins, as well as the in vivo induction of Phase II/III drug metabolizing enzymes/transporters in the mouse livers.