41. Methylenedioxy group and cyclooctadiene ring as structural determinants of schisandrin in protecting against myocardial ischemia-reperfusion injury in rats.

Yim TK, Ko KM.

As a preliminary investigation to exploring whether the methylenedioxy group and the cyclooctadiene ring of the dibenzo[a,c]cyclooctadiene (schisandrin) molecule plays an important role in the protection against myocardial ischemia-reperfusion (IR) injury, we examined the effects of three schisandrins, namely schisandrin A (Sch A), schisandrin B (Sch B), and schisandrin C (Sch C), and the effect of dimethyl-4,-4′-dimethoxy-5,6,5′,6′-dimethylene-dioxy-biphenyl-2,2′-bicarboxylate (DDB), an intermediate compound derived from the synthesis of Sch C, on myocardial IR injury in isolated Langendorff-perfused rat hearts. While pretreating rats with Sch A or DDB at a daily oral dose of 1.2 mmol/kg for 3 days did not protect the isolated-perfused hearts against IR-induced damage, pretreatment with Sch B or Sch C at the same dosage regimen produced cardioprotective action. The extent of cardioprotection afforded by Sch B or Sch C pretreatment correlated well with the degree of enhancement in myocardial glutathione antioxidant status, as indicated by significant increases in the tissue-reduced glutathione level and Se-glutathione peroxidase (EC, glutathione transferases (EC, and glutathione reductase (EC activities in ischemic-reperfused hearts when compared with the unpretreated IR control. Our results indicate that both the methylenedioxy group and the cyclooctadiene ring of the schisandrin molecule are important structural determinants in mediating the protection against myocardial IR injury.