Caulophine protects cardiomyocytes from oxidative and ischemic injury.
Caulophine is a new fluorenone alkaloid isolated from the radix of Caulophyllum robustum MAXIM and identified as 3-(2-(dimethylamino) ethyl)-4,5-dihydroxy-1,6-dimethoxy-9H-fluoren-9-one. Due to its new chemical structure, the pharmacological activities of caulophine are not well characterized. The present study evaluated the protective effect and the primary mechanisms of caulophine on cardiomyocyte injury. Viability of cardiomyocytes was assayed with the MTT method, and cell apoptosis was detected by flow cytometry. Myocardial infarction was produced by ligating the coronary artery, and myocardial ischemia was induced by isoproterenol in rats. Myocardial infarction size was estimated with p-nitro-blue tetrazolium staining. Lactate dehydrogenase (LDH), creatine kinase (CK), superoxide dismutase (SOD), malondialdehyde (MDA), and free fatty acid (FFA) were spectrophotometrically determined. Histopathological and ultrastructural changes of ischemic myocardium were observed. The results showed that pretreatment with caulophine increased the viability of H(2)O(2)- and adriamycin-injured cardiomyocytes; decreased CK, LDH, and MDA; increased SOD; and inhibited H(2)O(2)-induced cellular apoptosis. Caulophine reduced myocardial infarct size and serum CK, LDH, FFA, and MDA; raised serum SOD; and improved histopathological and ultrastructural changes of ischemic myocardium. The results demonstrate that caulophine has the ability to protect cardiomyocytes from oxidative and ischemic injury through an antioxidative mechanism that provides a basis for further study and development of caulophine as a promising agent for treating coronary heart disease.
Si
Kaiwei
K
Department of Pharmacology, Xi'an Jiaotong University School of Medicine, Xi'an, PR China.
Liu
Juntian
J
He
Langchong
L
Li
Xikuan
X
Gou
Wei
W
Liu
Chuanhao
C
Li
Xiaoqi
X
D000818:Animals; D003402:Creatine Kinase / Q000378:metabolism; D005230:Fatty Acids, Nonesterified / Q000378:metabolism; D005434:Flow Cytometry; D005449:Fluorenes / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects*; D006861:Hydrogen Peroxide / Q000494:pharmacology; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D009203:Myocardial Infarction / Q000378:metabolism* / Q000473:pathology; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D018384:Oxidative Stress; D051381:Rats; D017207:Rats, Sprague-Dawley; D013482:Superoxide Dismutase / Q000378:metabolism
D005230:Fatty Acids, Nonesterified; D005449:Fluorenes; C554063:caulophine; D008315:Malondialdehyde; D006861:Hydrogen Peroxide; D007770:L-Lactate Dehydrogenase; D013482:Superoxide Dismutase; D003402:Creatine Kinase