Coompo Research Chemicals

Schisandrin A and schisandrin B inhibited cytochrome P450 (CYP3A) activity with IC(50) values of 6.60 and 5.51 microM and K(i) values of 5.83 and 4.24 microM, respectively. A dilution assay plot of each inhibitor gave a slope value of up to 91% that of the control samples. The inactivation of CYP3A activity by schisandrin A and schisandrin B was found to be both time-and concentration-dependent (schisandrin A: K(I) = 4.51 microM, K(inact) = 0.134/min; schisandrin B: K(I) = 3.01 microM, K(inact) = 0.112/min). We conclude that the inhibition of CYP3A activity in rat liver microsomes by schisandrin A and schisandrin B is mostly attributed to a mixed noncompetitive and complete inhibition. Changes in the pharmacokinetic profiles of peroral MDZ in the rat model were contributed mainly to Schisandrin A inhibition of CYP3A activity. These results suggest that Schisandrin A, as an inhibitor of CYP3A, possesses a clinically beneficial property of altering the disposition of drugs metabolized by CYP3A.

Schisantherin A demonstrated strong and comparable activities to reverse the drug resistance and the intracellular drug accumulation in four mediated multidrug resistance (MDR) cell lines. Schisantherin A are potent P-gp inhibitor and is of potential for future clinical application.

Pretreating mice with Sch A at a daily oral dose of 1 mmol/kg for 3 days did not protect against CCl4 hepatotoxicity, whereas pretreatment with Sch B or Sch C at the same dosage regimen produced almost complete protection. The hepatoprotection afforded by Sch B or Sch C pretreatment was associated with significant increases in the hepatic mitochondrial GSH level and glutathione reductase (EC 1.6.4.2) activity. Our results indicate that the methylenedioxy group of the dibenzocyclooctadiene skeleton of schisandrin is an important structural determinant in the stimulation of hepatic mitochondrial GSH, particularly under conditions of CCl4 intoxication.