250 mg kg of grape seed proanthocyanidins extract (GSPE) administered to Wistar rats modulated the expression of liver clock genes.
GSPE influenced the expression of both Bmal1 and miR-27b-3p in the liver.
Both Bmal1 and miR-27b-3p exhibited a in their expression.
There was a negative interaction observed between Bmal1 and miR-27b-3p.
GSPE may adjust the hepatic peripheral clock through miRNA modulation.
In vitro studies indicated that Bmal1 is sensitive to GSPE, but this effect did not involve miR-27b-3p.
Simplified
SCOPE: 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 (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 kgof 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). However, this effect is independent of miR-27b-3p. -1 -1
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.
Key numbers
250 mg/kg
GSPE Dose
Administered to Wistar rats before a 6-hour jet lag.
3 hours after lights off
miR-27b-3p Expression Increase
Observed significant upregulation in treated jet lag group.
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