Transforming growth factor and nuclear factor kappa B mediated prophylactic cardioprotection by total flavonoids of fructus chorspondiatis in myocardial ischemia.
BACKGROUND
Chorspomias axillaries Batt et Hill, a well-known Chinese herb, has been used in clinical treatment of angina pectoris for hundreds of years, but its effective components and intrinsic cardioprotective mechanism are still beyond us.


OBJECTIVE
In this study, we extracted Total Flavonoids of Fructus Chorspondiatis (TFFC), a potential effective component from Chorspomias axillaries Batt et Hill to investigate its effect on myocardial ischemia induced by isoproteronol in rat and elucidated its probable mechanism.


RESULTS
The results showed that prophylactically ;;intragastrical administration of TFFC at the dose of 200 mg/kg body weight effectively suppressed the variation of J points in electrocardiogram (0.211 +/- 0.059( )mV versus 0.277 +/- 0.046( )mV, p < 0.05) and inhibited the upregulated serum level of creatine kinase (754 +/- 114( )U/l versus 1,112 +/- 239( )U/l, p < 0.05), creatine kinase -MB (700 +/- 95( )U/l versus 1,012 +/- 252( )U/l, p < 0.05) and lactate dehydrogenase (1,174 +/- 200( )U/l versus 2,025 +/- 975( )U/l, p < 0.05) in myocardial ischemia, revealing its cardioprotective effect. It increased a potent tissue protective polypeptide, transforming growth factor beta(1) (TGF-beta(1)) level as well as its receptors TbetaRI and TbetaRII(p < 0.05) and significantly inhibited the expression of a redox-sensitive transcription factor, nuclear factor kappa B (NF-kappaB).


CONCLUSIONS
These data demonstrated that TFFC at the dose of 200 mg/kg body weight exerts prophylactically cardioprotective effect during ischemia injury. Part of its cardioprotective mechanism may relate to induction of TGF-beta(1) to competitively inhibit NF-kappaB signaling pathway. Prophylactically exogenous administration with the component may serve as a novel therapeutic strategy for ischemic cardiovascular diseases.
Department of Integrative Medicine, Medical College, Jinan University, Huang Pu Da Dao Xi 601#, Guangzhou 510632, People's Republic of China. Taojn@jnu.edu.cn
Jienan
J
Ao
Huijuan
H
Feng
Fang
F
Xia
D000818:Animals; D002316:Cardiotonic Agents / Q000302:isolation & purification / Q000494:pharmacology*; D003402:Creatine Kinase / Q000097:blood / Q000187:drug effects; D052279:Creatine Kinase, MB Form / Q000097:blood / Q000187:drug effects; D004365:Drugs, Chinese Herbal / Q000302:isolation & purification / Q000494:pharmacology*; D004562:Electrocardiography; D005260:Female; D005419:Flavonoids / Q000302:isolation & purification / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects; D007770:L-Lactate Dehydrogenase / Q000097:blood / Q000187:drug effects; D008297:Male; D017202:Myocardial Ischemia / Q000139:chemically induced / Q000188:drug therapy*; D016328:NF-kappa B / Q000187:drug effects*; D010944:Plants / Q000737:chemistry; D017346:Protein Serine-Threonine Kinases / Q000187:drug effects / Q000378:metabolism; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D000077293:Receptor, Transforming Growth Factor-beta Type I; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018125:Receptors, Transforming Growth Factor beta / Q000187:drug effects / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000187:drug effects / Q000378:metabolism
D002316:Cardiotonic Agents; D004365:Drugs, Chinese Herbal; D005419:Flavonoids; D016328:NF-kappa B; D018125:Receptors, Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D007770:L-Lactate Dehydrogenase; D017346:Protein Serine-Threonine Kinases; D000077293:Receptor, Transforming Growth Factor-beta Type I; D000077294:Receptor, Transforming Growth Factor-beta Type II; C000625843:Tgfbr1 protein, rat; D003402:Creatine Kinase; D052279:Creatine Kinase, MB Form