# Eurycoma longifolia (Tongkat Ali) supplementation enhances sleep and wake consolidation in wild-type, but not in narcoleptic mice

## TL;DR

Tongkat Ali improves sleep and wake patterns in healthy mice but not in narcoleptic mice, suggesting it may help with sleep consolidation in normal aging.

## Contribution

The study reveals that Tongkat Ali enhances sleep-wake consolidation in wild-type mice but not in narcoleptic models.

## Key findings

- TA supplementation consolidated wakefulness and NREM sleep in wild-type mice.
- TA increased slow wave activity during the active period in wild-type mice.
- DTA mice showed no improvement in sleep or wake cycles with TA supplementation.

## Abstract

Tongkat Ali (TA), also known as Eurycoma longifolia, has been used as a traditional herbal medicine for anti-aging, evidenced by clinical trials presenting the beneficial effects on energy, fatigue, and mood disturbance. We have recently shown that TA supplementation dose-dependently enhances the rest–activity pattern in C57BL/6 mice. Since destabilization of wakefulness and sleep is one of the typical symptoms of not only the elderly but also narcolepsy, we performed sleep analysis with and without dietary TA extract supplementation in middle-aged (10–12 months old) wild-type (WT) and narcoleptic DTA mice. We found that TA supplementation enhanced diurnal rhythms of locomotion and temperature in a time-of-day-dependent manner in WT mice but attenuated in DTA mice. In WT mice, TA supplementation consolidated wakefulness with a long bout duration and led to less entries into the sleep state during the active period, while it consolidated NREM sleep with long bout duration during the resting period. Neither disturbed sleep and wake cycles nor cataplexy was sufficiently improved in DTA mice. EEG spectral analysis revealed that TA supplementation enhanced slow wave activity (SWA) at both delta and low delta frequencies (0.5–4.0 and 0.5–2.0 Hz) during the light period, suggesting TA extract may induce vigilance during the active period, which then elicits a rebound effect during the resting period. Interestingly, DTA mice also slightly, but significantly, increased SWA at low frequencies during the light period. Taken together, our results suggest that TA supplementation enhances the Yin-Yang balance of sleep, temperature, and locomotion in WT mice, while its efficacy is limited in narcoleptic mice.