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. This study has 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 is to evaluate if the activity of GSPE as modulator of hepatic clock genes can be mediated by miRNAs. Methods and results 250 mg kg(-1) of GSPE is administered to Wistar rats before a 6-h jet lag and sacrificed at different time points. GSPE modulated both expression of Bmal1 and miR-27b-3p in the liver. Cosinor-based analysis reveals that both Bmal1 and miR-27b-3p expression follow a circadian rhythm, a negative interaction between them, and the role of GSPE adjusting the hepatic peripheral clock via miRNA. Additionally, in vitro studies show that Bmal1 is sensitive to GSPE (25 mg L-1). However, this effect is 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.

Automated summary

This study investigates the modulation of hepatic clock genes by grape seed proanthocyanidins extract (GSPE) through miRNAs. The results demonstrate that GSPE regulates the expression of Bmal1 and miR-27b-3p in the liver, and the modulation of peripheral clocks by GSPE via miRNA may involve a complex mechanism that interacts with the central system.