A novel phytochemical, digoxigenin-3-O-rutin in the amelioration of isoproterenol-induced myocardial infarction in rat: a comparison with digoxin.
BACKGROUND
The commonly used cardiac glycoside, digoxin (DIG), has a narrow therapeutic window. Although some investigations were made to counteract its toxic effects, no alternate phytochemical is available till date that is more potent and safer than DIG.


OBJECTIVE
Our main aim was to isolate a novel cardenolide from the seeds of Trigonella foenum graceium and to evaluate its relative potential in comparison to that of DIG.


METHODS
In one experiment effects of the isolated compound at 2.5, 5.0, and 10 mg/kg (p.o.) were evaluated in isoproterenol (ISO)-induced cardiovascular problems in rats. As the test drug (TDR) reversed most of the ISO-induced changes, it was subjected to the phytochemical analyses and was identified as digoxigenin-3-O-rutin. In another experiment effects of DIG and rutin (Rtn) were compared with those of TDR or DIG alone. The hydroxyl radical scavenging activity was also measured by electron spin resonance (EPR).


RESULTS
digoxigenin-3-O-rutin at 10 mg/kg markedly reduced the ISO-induced increase in cardiac lipid peroxidation and in the levels of serum creatinine phosphokinase-MB, glutamate oxaloacetate transaminase, glutamate pyruvate transaminase, lactate dehydrogenase, and creatinine. It also reversed the ISO-induced changes in the cardiac histomorphology. Interestingly TDR appeared to be more effective than DIG alone or DIG and Rtn in combination.


CONCLUSIONS
The newly isolated digoxigenin-3-O-rutin appears to be more potent and safe than digoxin. Its higher efficacy could be due to its structural specificity and might have been mediated through its better free radical scavenging action.
School of Life Sciences, Devi Ahilya University, Takhshila Campus, Indore, Madhya Pradesh, India. spanda4@rediffmail.com
Sunanda
S
Panda
Anand
A
Kar
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D001219:Aspartate Aminotransferases / Q000097:blood; D015415:Biomarkers / Q000097:blood; D002316:Cardiotonic Agents / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology* / Q000633:toxicity; D003401:Creatine / Q000097:blood; D052279:Creatine Kinase, MB Form / Q000097:blood; D004076:Digoxigenin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology* / Q000633:toxicity; D004077:Digoxin / Q000494:pharmacology* / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D004578:Electron Spin Resonance Spectroscopy; D016166:Free Radical Scavengers / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology* / Q000633:toxicity; D017665:Hydroxyl Radical / Q000737:chemistry; D007545:Isoproterenol; D007770:L-Lactate Dehydrogenase / Q000097:blood; D015227:Lipid Peroxidation / Q000187:drug effects; D009203:Myocardial Infarction / Q000097:blood / Q000139:chemically induced / Q000188:drug therapy*; D009206:Myocardium / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012431:Rutin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology / Q000633:toxicity; D012639:Seeds; D029910:Trigonella / Q000737:chemistry
D000975:Antioxidants; D015415:Biomarkers; D002316:Cardiotonic Agents; D016166:Free Radical Scavengers; C574697:digoxigenin-3-O-rutin; D017665:Hydroxyl Radical; D012431:Rutin; D004077:Digoxin; D007770:L-Lactate Dehydrogenase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D052279:Creatine Kinase, MB Form; D007545:Isoproterenol; D003401:Creatine; D004076:Digoxigenin