Abstract

This study investigated delayed protection of Ferulic acid (FA), a natural polyphenol commonly found in fruits, vegetables and whole grains. Hearts of mice that were fed a FA diet were protected against ischemia/reperfusion (I/R) injury, even if FA-containing chow was replaced with standard chow for 27h before initiating I/R. FA showed an increased recovery in cardiac function and reduction in infarct size. These findings were confirmed in cardiomyocytes that were pretreated with FA, 24h before anoxia/reoxygenation. Moreover, FA significantly upregulated HSP70 expression. Selective knockdown of HSP70, FA treatment failed to render resistance to I/R. Additionally, FA induced an increase in NO production, and activated ERK1/2. The delayed protection of FA was abolished by NOS inhibitor L-NAME, or ERK1/2 inhibitor PD184352. Treatment with L-NAME or PD184352 inhibited HSP70 upregulation. In conclusion, FA treatment results in delayed cardioprotection against I/R, which is mediated through upregulation of HSP70 via NO-ERK1/2 pathway.

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