Abstract
Cinnamic acid (CA) derivatives have recently received focus due to their anticancer, antioxidant, and antidiabetic properties. The present study aimed to determine the effects of cinnamic acid on the circadian clock, which is a cell-autonomous endogenous system that generates circadian rhythms that govern the behavior and physiology of most organisms. Cinnamic acid significantly shortened the circadian period of PER2::LUC expression in neuronal cells that differentiated from neuronal progenitor cells derived from PER2::LUC mouse embryos. Cinnamic acid did not induce the transient mRNA expression of clock genes such as Per1 and Per2 in neuronal cells, but significantly shortened the half-life of PER2::LUC protein in neuronal cells incubated with actinomycin D, suggested that CA post-transcriptionally affects the molecular clock by decreasing Per2 mRNA stability. A continuous infusion of CA into mice via an Alzet osmotic pump under constant darkness significantly shortened the free-running period of wheel-running rhythms. These findings suggest that CA shortens the circadian period of the molecular clock in mammals.
Highlights
The central clock located in the suprachiasmatic nucleus (SCN) of the anterior hypothalamus governs various behavioral and physiological circadian rhythms in mammals such as sleep/wake cycles, body temperature and blood pressure [1]
The present study found that Cinnamic acid (CA) dose-dependently shortens the circadian period of the molecular clock by monitoring bioluminescence in neuronal cells derived from PER2::LUC mice
We evaluated whether caffeine and lithium affect rhythmic PER2::LUC activity in neuronal cells derived from
Summary
The central clock located in the suprachiasmatic nucleus (SCN) of the anterior hypothalamus governs various behavioral and physiological circadian rhythms in mammals such as sleep/wake cycles, body temperature and blood pressure [1]. Functional clock molecules are essential to maintain the normal periodicity of behavioral rhythms [4]. Deletion of other clock genes such as Per, Clock, Cry, and Cry affects the free-running period of circadian behavior in a gene-specific manner, whereas Bmal knockout results in behavioral arrhythmicity under constant darkness [4]. Perturbed clock function is implicated in numerous pathologies including sleep disorders associated with circadian rhythms, psychiatric conditions, hypertension, cardiovascular diseases, cancer and metabolic disorders [3]. Vegetables and flowers, and have attracted attention due to their anticancer, antimicrobial, antioxidant and antidiabetic properties [10,11]. Cinnamic acid derivatives such as ferulic acid and cinnamide derivatives have neuronal effects including anticonvulsant, antidepressant, neuroprotective, analgesic, anti-inflammatory, muscle re-. B27 were purchased from Life Technologies (Carlsbad, CA, USA)
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