Cordycepin Increases Nonrapid Eye Movement Sleep via Adenosine Receptors in Rats

Abstract

Cordycepin (3′-deoxyadenosine) is a naturally occurring adenosine analogue and one of the bioactive constituents isolated from Cordyceps militaris/Cordyceps sinensis, species of the fungal genus Cordyceps. It has traditionally been a prized Chinese folk medicine for the human well-being. Because of similarity of chemical structure of adenosine, cordycepin has been focused on the diverse effects of the central nervous systems (CNSs), like sleep regulation. Therefore, this study was undertaken to know whether cordycepin increases the natural sleep in rats, and its effect is mediated by adenosine receptors (ARs). Sleep was recorded using electroencephalogram (EEG) for 4 hours after oral administration of cordycepin in rats. Sleep architecture and EEG power spectra were analyzed. Cordycepin reduced sleep-wake cycles and increased nonrapid eye movement (NREM) sleep. Interestingly, cordycepin increased θ (theta) waves power density during NREM sleep. In addition, the protein levels of AR subtypes (A1, A2A, and A2B) were increased after the administration of cordycepin, especially in the rat hypothalamus which plays an important role in sleep regulation. Therefore, we suggest that cordycepin increases theta waves power density during NREM sleep via nonspecific AR in rats. In addition, this experiment can provide basic evidence that cordycepin may be helpful for sleep-disturbed subjects.

Sleep-Aids Derived from Natural Products

“…The signal of EEG was measured for 6 hours between 11:00 am and 5:00 pm. Each group has 5–6 rats ( Hu et al ., 2013 ).…”

“…However, cordycepin ( Cordyceps militaris/sinensis ) increased theta waves power density during NREM sleep. Adenosine receptors (AR) subtypes (A1, A2A and A2B) were over-expressed by cordycepin, and they are showing non-specific AR activation ( Hu et al ., 2013 ).…”

Cordycepin Suppresses Thymic Stromal Lymphopoietin Expression <i>via</i> Blocking Caspase-1 and Receptor-Interacting Protein 2 Signaling Pathways in Mast Cells

“…11,12) In this study, we first reported that cordycepin inhibited the level of TSLP by down-regulating caspase-1, RIP2, IKKβ, and NF-κB signal cascade in activated mast cells.…”

3’-Deoxyadenosine (Cordycepin) Produces a Rapid and Robust Antidepressant Effect via Enhancing Prefrontal AMPA Receptor Signaling Pathway

“…Other beneficial effects of 3’-dA, such as the anti-viral and anti-fungal effects, may also provide additional benefits to depressed patients, because viral or fungal infections contribute to or even cause depressive symptoms ( Tuli et al, 2013 ). 3’-dA also improves the quality of sleep by increasing non-rapid eye movement sleep ( Hu et al, 2013 ). Therefore, 3’-dA is considered relatively safe and beneficial for use as a potential novel antidepressant drug.…”

“…Moreover, 3’-deoxyadenosine (3’-dA, Cordycepin), one of the major bioactive metabolites in the Cordyceps Militaris ( Tuli et al, 2013 ), exerted a beneficial effect in a 6-week chronic unpredictable mild stress (CUMS) mouse model via the forced swim test (FST; Tianzhu et al, 2014 ). 3’-dA possesses a wide range of beneficial effects of therapeutic potential, including anti-insomnia, anti-inflammatory, anti-cancer, anti-viral, and anti-fungal activities ( Hu et al, 2013 ; Tuli et al, 2013 ). However, whether or not 3’-dA has a fast-acting antidepressant effect remains unknown.…”