Terpene trilactones from Ginkgo biloba have been investigated extensively for their
antioxidant and anti-ischaemic activities on the brain and the heart, but the mechanisms of these effects remain unclear. For the present study, a
terpenoid constituent from G. biloba,
bilobalide, was screened for protective effects on the ischaemic heart and the involvement of the PAFR [PAF (
platelet-activating factor) receptor] and the
enzyme that degrades PAF, PAF-AH (
PAF acetylhydrolase) during
hypoxia. The PAF pathway is supposed to play a role in
hypoxia and its regulation may prevent or alleviate MI (
myocardial infarction). Cardiomyocytes from neonatal rat hearts were cultured and treated with different concentrations of
bilobalide (500-0.5 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 RT-PCR (reverse transcription PCR) respectively. With the MI model we tested for
bilobalide's cardioprotective effects and the involvement of PAFR and PAF-AH.
Bilobalide (5 ng/ml) significantly decreased the mortality of cells in a concentration-dependent way.
mRNA expression of PAFR was up-regulated in hypoxic cells but in the groups treated with
bilobalide, its expression was down-regulated to the level of the normal control. In hypoxic tissue, PAFR
protein expression was also up-regulated, but was reduced in the
bilobalide (10 mg/kg of
body weight) treated group. 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.