Anti-ischemic Effects Of Bilobalide On The Rat Heart And The Involvement Of The Platelet-Activating Factor Receptor

Terpene trilactones from Ginkgo biloba have been investigated intensively for their anti-oxidant and anti-ischemic activities on the brain and the heart but the mechanisms of these effects remain unclear. For this study, a terpenoid constituent from Ginkgo biloba, bilobalide, was screened for protective effects on the ischemic heart and the involvement of the platelet-activating factor receptor (PAFR) and the enzyme that degrades PAF, Platelet-Activating Factor Acetylhydrolase (PAF-AH) during hypoxia.The PAF pathway is supposed to play a role in hypoxia and its regulation may prevent or alleviate myocardial infarction. Cardiomyocytes from neonatal rat hearts and endothelial cells were cultured and treated with different concentrations of bilobalide (0.5-500 ng/ml). After being subjected to a hypoxic environment, the cells’viability was evaluated and proteins as well as RNA were extracted for analysis by Western Blotting and Reverse-Transcription Polymerase Chain Reaction (RT-PCR), respectively.With the myocardial infarction model in rats we tested for bilobalide’s cardioprotective effects and the involvement PAFR and PAF-AH in vivo. Two trials were performed, the first one aiming at showing protective effects of bilobalide when administered before myocardial infarction, the second to evaluate curative effects of the drug in heart failure following myocardial infarction. Mortality, infarct size, lung to body weight ratio, weight, echocardiographic data and images of the coronary arteries obtained by coronary angiography using synchrotron radiation were used to evaluate the cardioprotective effects of bilobalide in the two trials.Bilobalide (5 ng/ml) significantly decreased the mortality of cardiomyocytes and endothelial cells in a concentration dependent way. mRNA expression of PAFR was upregulated in hypoxic cells but in the groups treated with bilobalide, its expression was downregulated to the level of the normal control in cardiomyocytes. In hypoxic tissue, PAFR protein expression was also upregulated but was reduced in the bilobalide (10 mg/kg i.p.) treated group. Two in vivo trials didn’t give convincing evidence that bilobalide exerts cardioprotective effects in the animal model as well.Our results indicate that PAF and its receptor may be involved in the cellular response of cardiomyocytes to hypoxia and that bilobalide may interact with this receptor to exert its cardioprotective effects in vitro. Subsequent research should focus on finding the right conditions for this cardioprotective effect in vivo as well.