Methylenedioxy group and cyclooctadiene ring as structural determinants ofschisandrin in protecting against myocardial ischemia-reperfusion injury in rats

As a preliminary investigation to exploring whether the methylenedioxy grou p and the cyclooctadiene ring of the dibenzo[a,c]cyclooctadiene (schisandri n) molecule plays an important role in the protection against myocardial is chemia-reperfusion (IR) injury, we examined the effects of three schisandri ns, 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-d ioxy-biphenyl-2,2'-bicarboxylate (DDB), an intermediate compound derived fr om 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 or al dose of 1.2 mmol/kg for 3 days did not protect the isolated-perfused hea rts against IR-induced damage, pretreatment with Sch B or Sch C at the same dosage regimen produced cardioprotective action. The extent of cardioprote ction afforded by Sch B or Sch C pretreatment correlated well with the degr ee of enhancement in myocardial glutathione antioxidant status, as indicate d by significant increases in the tissue-reduced glutathione level and Se-g lutathione peroxidase (EC 1.11.1.9), glutathione transferases (EC 2.5.1.18) , and glutathione reductase (EC 1.6.4.2) 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 schi sandrin molecule are important structural determinants in mediating the pro tection against myocardial IR injury. (C) 1998 Elsevier Science Inc.