Resveratrol, a constituent of red wine, and γ-tocotrienol, a constituent of palm 
oil are important for cardioprotection. Although microRNAs are known regulators 
for genes involved in cardiac remodelling, the regulatory pathway involving 
microRNA has not been studied so far. We explored the cardioprotection by 
resveratrol, longevinex and γ-tocotrienol in ischaemia/reperfusion(I/R) model of 
rat and determined miRNA profile from isolated RNA. Systemic analyses of miRNA 
array and theirs targets were determined using a number of computational 
approaches. Resveratrol and γ-tocotrienol, either alone or in combination, 
modulated the expression pattern of miRNAs close to the control level based on 
PCA analyses. Differential expression was observed in over 75 miRNAs, some of 
them, such as miR-21 and miR-20b (anti-angiogenic) were previously implicated in 
cardiac remodelling. The target genes for the highest differentially expressed 
miRNA include genes of various molecular functions such as TGFβ1-Smad3 
signalling pathway, inflammation and their transcription factors, which may play 
key role in reducing I/R injury. Administration of antagomiR-20 attenuated I/R 
induced vascular endothelial growth factor and HIF1α level. All the 
interventions treated for 3 weeks lead to significant cardioprotection against 
ischaemia/reperfusion injury. A unique signature of miRNA profile is observed in 
control heart pretreated with resveratrol or γ-tocotrienol. We have determined 
specific group of miRNA in heart that have altered during IR injuries. Most of 
those altered microRNA expressions modulated close to their basal level in 
resveratrol or longevinex treated I/R rat. Interestingly, resveratrol and 
γ-tocotrienol resulted in synergestic action.