Protective Effect of Saponins from Panax notoginseng against Doxorubicin-Induced Cardiotoxicity in Mice

The dried rhizome of Panax notoginseng is a traditional Chinese herb extensively used for treatment of cardiovascular diseases and other ailments. Panax notoginseng saponins (PNS) are known as the major pharmacologically active constituents. The purpose of this study was to investigate the cardioprotective effects of PNS against doxorubicin-induced cardiotoxicity and its possible influence on the anti-tumor activity of doxorubicin. Five groups of ICR mice were treated with saline (control group), doxorubicin alone (20 mg/kg i. p. ), PNS alone, doxorubicin pretreated with PNS (100 mg/kg i. g. for 5 consecutive days) or amifostine (single dose of 200 mg/kg i. v. , used as positive control). After 72 h of doxorubicin treatment, cardiac function, serum levels of lactate dehydrogenase (LDH), creatine kinase (CK) and creatine kinase isoenzyme (CK-MB) and activities of antioxidant enzymes in heart tissue were measured. Pretreatment with PNS significantly protected the mice from DOX-induced cardiotoxicity as evidenced from improved ventricular contractile function, lower levels of serum LDH, CK and CK-MB, minimal morphological changes in hearts, and normalization of myocardial superoxide dismutase, glutathione peroxidase and catalase activities. Additionally, in vitro cytotoxic studies demonstrated that PNS did not compromise the inhibitory effect of doxorubicin on the proliferation of cancer cells. These results imply the potentially clinical application of PNS to overcome the negative side effects of doxorubicin. Abbreviations CAT:catalase CK:creatine kinase CK-MB:creatine kinase isoenzyme DOX:doxorubicin ±dP/dt:first derivative of left ventricular pressure over time GSH-Px:glutathione peroxidase HR:heart rate LDH:lactate dehydrogenase LVEDP:left ventricular end-diastolic pressure LVSP:left ventricular systolic pressure PNS: Panax notoginseng saponins SOD:superoxide dismutase