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Grape seed proanthocyanidins modulate the hepatic molecular clock via microRNAs.

SCOPE
Circadian rhythm is an endogenous and self-sustained timing system, responsible for the coordination of daily processes in 24-h timescale. It is regulated by an endogenous molecular clock, which is sensitive to external cues as light and food. We have previously shown that grape seed proanthocyanidins extract (GSPE) regulates the hepatic molecular clock. Moreover, GSPE is known to interact with some microRNAs (miRNAs). Therefore, the aim of this study was to evaluate if the activity of GSPE as modulator of hepatic clock genes could be mediated by miRNAs.


METHODS AND RESULTS
250 mg/kg of GSPE was administered to Wistar rats before a 6-hour jet lag and sacrificed at different time points. GSPE modulated both expression of Bmal1 and miR-27b-3p in the liver. Cosinor-based analysis revealed that both Bmal1 and miR-27b-3p expression followed a circadian rhythm, a negative interaction between them, and the role of GSPE adjusting the hepatic peripheral clock via miRNA. Additionally, in vitro studies showed that Bmal1 was sensitive to GSPE (25 mg/L). However, this effect was independent of miR-27b-3p.


CONCLUSION
miRNA regulation of peripheral clocks via GSPE may be part of a complex mechanism that involves the crosstalk with the central system rather than a direct effect. This article is protected by copyright. All rights reserved.