Inhibition of glutathione-S-transferase by total saponins of Panax notoginseng and its kinetics analysis in liver of mice / 中国中药杂志

<p><b>OBJECTIVE</b>To study the inhibition of glutathione-s-transferase by total saponins of Panax notoginseng and its kinetics analysis in liver of mice.</p><p><b>METHOD</b>Mouse liver cytochyma enzyme was obtained by different velocity centrifugation, the mouse liver glutathione-S-transferase of michaelis constant (Km), maximum velocity (Vmax) and the inhibition of glutathione-S-transferase by total saponins of P. notoginseng of 50% inhibiting concentration (IC50), inhibition constant (KI, KIS), the type of inhibition were calculation by Lineweaver-Burk and the low of semi-effet-probit.</p><p><b>RESULT</b>It was found that total saponins of P. notoginseng inhibited the glutathione-S-transferase activity with IC50 of 189.54 mg x L(-1). Kinetics analysis showed the glutathione-S-transferase of Km was 0.4563 mmol x L(-1) and Vmax was 476.19 U x mg(-1) with reduced glutathione (GSH) substrate, 0.1097 mmol x L(-1) (Km) and 400.00 U x mg(-1) (Vmax) with 1-chloro-2,4-dinitrobenzene (CDNB) substrate. Kinetics studies of total saponins of P. notoginseng on glutathione-S-transferase showed the inhibition were belong to mix-type with GSH and CDNB; the inhibition constant was 0.27 mg x L(-1) (KI), 0.68 mg x L(-1) (KIS) with GSH, and 0.21 mg x L(-1) (KI), 0.66 mg x L(-1) (KIS) with CDNB.</p><p><b>CONCLUSION</b>Total saponins of P. notoginseng strongly inhibited the glutathione-S-transferase activity.</p>

Effect of Panax notoginseng on genes expression of CYP and GST in liver tissues of rats / 中国中药杂志

<p><b>OBJECTIVE</b>To examine the effects of Panax notoginseng on the expression of cytochrome P450 (CYP) genes and glutathione S-trans-ferase (GST) genes in liver tissues of male SD rats.</p><p><b>METHOD</b>Rats were administered P. notoginseng 2 or 4 g x kg(-1) bw/d by gavage daily for 14 days. The levels of gene expression of CYP1A1, CYP1A2, CYP2B1, CYP2E1, CYP3A1, CYP4A1, and GSTml, GST-pi were examined by quantitative real-time reverse-transcription polymerase chain reaction (quantitative real time-RT-PCR) assays.</p><p><b>RESULT</b>The expression of CYP1A1, CYP1A2, CYP2E1, CYP3A1, GSTml and GST-pi genes was not changed by 2 or 4 g x kg(-1) P. notoginseng treatment, But P. notoginseng significantly inhibited mRNA expressions of CYP2B1 (0.48-fold, P < 0.05, and 0.61-fold, P < 0.05, respectively) and CYP 4A1 (0.69-fold, and 0. 51-fold, respectively).</p><p><b>CONCLUSION</b>P. notoginseng had a special inhibitory selectivity on the expression of CYP2B1 and CYP4A1 genes in liver tissues of rats, which indicated it may be one of the mechanisms of actions of P. notoginseng. P. notoginseng had no effects on the expressions of CYP1A1, CYP1A2, CYP2E1 and CYP3A1 genes, which suggested when P. notoginseng co-administrated with those drugs metabolized by the above major metabolizing enzymes in liver, metabolic herb-drug interactions would not be happened.</p>

Effect of Panax notoginseng on genes expression of CYP and GST in lung tissues of rats / 中国中药杂志

<p><b>OBJECTIVE</b>To examine the effects of Panax notoginseng on the expression of cytochrome P450 (CYP) genes and glutathione S-transferase (GST) genes in lung tissues of male SD rats.</p><p><b>METHOD</b>Rats were administered P. notoginseng 2 or 4 g X kg(-1) bw/d by gavage daily for 15 days. The levels of gene expression of CYP1A1, CYP1A2, CYP1B1, CYP2B1, CYP2E1, CYP3A1, CYP4A1 and glutathione S-transferase ml (GST-ml) and glutathione S-transferase pi (GST-pi) were examined by quantitative real-time reverse-transcription polymerase chain reaction (quantitative real time-RT-PCR) assays.</p><p><b>RESULT</b>The expression of CYP2E1, CYP1A2 and GST-pi genes was not changed by P. notoginseng treatment, however, 2 g * kg-1 dose of P. notoginseng gave a 4.00-fold (P < 0.05) induction of CYP3A1 mRNA. P. notoginseng significantly increased mRNA expressions of GSTml (1.64-fold, P <0. 05 and 1.53-fold, P > 0.05) and CYP1A1 (3.44-fold, P > 0.05 and 6.05-fold, P < 0.05) in the 2 g x kg(-1) and 4 g x kg(-1) bw/d treatment groups, respectively, but P. notoginseng had a inhibitory tendency on mRNA expressions of CYP1B1 (0.81-fold, P > 0.05 and 0.38-fold, P > 0.05) and significantly inhibited the expressions of CYP2B1 (0.47-fold, P < 0.05 and 0.50-fold, P < 0.05) and CYP4A1 (0.54-fold, P < 0.05 and 0. 72-fold, P < 0.05) genes in the two groups.</p><p><b>CONCLUSION</b>A specific effect of P. notoginseng on the expression of different cytochrome P-450 genes or glutathione S-transferase genes in the lung tissues of rats was observed in this investigation. These findings would be very important and helpful for studying the mechanism of action of P. notoginseng and its reasonable use in clinic.</p>

Inhibition of glutathione-S-transferase by dihydromyricetin and its kinetics analysis in liver of mice / 中国药理学通报

Aim To study the inhibition of glutathione-S-transferase by dihydromyricetin and its kinetics analysis in liver of mice.Methods Mouse liver cytochyma enzyme was obtained by different velocity centrifugation,the mouse liver glutathione-S-transferase of michaelis constant(Km),maximum velocity(Vmax)and the inhibition of glutathione-S-transferase by dihydromyricetin of 50% inhibiting concentration(IC50),inhibition constant(Ki),the type of inhibition were calculated by Lineweaver-Burk and the low of semi-effect-probit.Results It was found that dihydromyricetin inhibited the glutathione-S-transferase activity with an IC50 of(121.14?13.66)?mol?L~-1.Kinetics analysis showed the Km was 0.1460 mmol?L~-1 and Vmax was 175.44 U?mg~-1 for reduced glutathione(GSH)substrate and 0.0937 mmol?L~-1(Km)and 212.77 U?mg~-1(Vmax)for 1-chloro-2,4,-dinitrobenzene(CDNB)substrate.Kinetics studies of dihydromyricetin on glutathione-S-transferase showed the inhibition was competitive with GSH and noncompetitive with CDNB,and the inhibition constant was 0.22 mmol?L~-1 with GSH and 0.54 mmol?L~1 with CDNB.Conclusion Dihydromyricetin can inhibit the glutathione-S-transferase activity in liver of mice.