Protective roles of Asperosaponin VI, a triterpene saponin isolated from Dipsacus asper Wall on acute myocardial infarction in rats.
Asperosaponin VI is a saponin of the medicinal herb Dipsacus asper (Xuduan), and no pharmacological activity has been reported yet. In this study, we investigated the anti-myocardial ischemia effects of Asperosaponin VI (ASA VI) both in vivo and in vitro. An animal model of myocardial ischemia(MI) injury was induced by coronary occlusion, pretreatment with ASA VI (10 and 20mg/kg, i.v.) could protect the heart from ischemia injury by decreasing the levels of creatine kinase-MB (CK-MB), lactate dehydrogenase (LDH), glutamic oxalacetic transaminase (GOT) and cardiac troponin T (cTnT) in serum, increasing the levels of catalase, glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) levels in heart, and decreasing that of malondialdehyde (MDA) level in acute MI rats. ASA VI also raised the activities of mitochondrial enzymes (succinate dehydrogenase (SDH), isocitrate dehydrogenase (ICDH), malate dehydrogenase (MDH) and alpha-ketoglutarate dehydrogenase (alpha-KGDH)) and those of adenosine triphosphate (ATP) content, but lowered Ca(2+) level. Electrocardiograph parameters and histopathological observations demonstrated the same protective effects. In vitro experiment, neonatal rat cardiomyocytes were incubated to test the direct cytoprotective effect of ASA VI against H(2)O(2) exposure. Pretreatment with ASA VI (30 and 60 microg/ml) prior to H(2)O(2) exposure increased cell viability and inhibited H(2)O(2)-induced reactive oxygen species increase. ASA VI (15, 30 and 60 microg/ml) also increased the activities of LDH in the cultured supernatant and SOD in cardiomyocytes, but decreased the cardiomyocytes MDA level. Our results suggested that ASA VI could provide significant cardioprotective effects against acute MI in rats. The mechanisms might be attributed to scavenging lipid peroxidation products and reactive oxygen species, increasing antioxidant defense enzymes and preventing mitochondrial damage.
Li
Chunmei
C
School of Pharmacy, Yantai University, Yantai, Shandong 264005, PR China.
Liu
Zhifeng
Z
Tian
Jingwei
J
Li
Guisheng
G
Jiang
Wanglin
W
Zhang
Guanbo
G
Chen
Fangfang
F
Lin
Peiyan
P
Ye
Zuguang
Z
D000818:Animals; D000831:Animals, Newborn; D002478:Cells, Cultured; D049917:Dipsacaceae / Q000737:chemistry*; D004562:Electrocardiography; D006321:Heart / Q000187:drug effects / Q000503:physiopathology; D006861:Hydrogen Peroxide / Q000494:pharmacology; D008297:Male; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D009203:Myocardial Infarction / Q000209:etiology / Q000517:prevention & control*; D017202:Myocardial Ischemia / Q000097:blood / Q000150:complications / Q000378:metabolism / Q000473:pathology; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D012503:Saponins / Q000302:isolation & purification* / Q000494:pharmacology*; D015996:Survival Rate; D014315:Triterpenes / Q000302:isolation & purification* / Q000494:pharmacology*
D012503:Saponins; D014315:Triterpenes; C534004:akebia saponin D; D006861:Hydrogen Peroxide