# Cornelian Cherry (Cornus mas) Fruit Extract Administration in Sleep Deprived Wistar Rats—Friend or Foe?

## TL;DR

This study explores how Cornelian cherry extract affects organ damage in sleep-deprived rats, finding mixed results including some protection and unexpected harm.

## Contribution

The study reveals that antioxidant supplements like Cornelian cherry extract may have mixed effects, offering protection in some organs while causing harm in others during sleep deprivation.

## Key findings

- Cornelian cherry extract partially protected the liver from sleep deprivation-induced damage.
- The extract unexpectedly increased lipid oxidative damage in the aorta.
- Sleep deprivation caused oxidative stress and inflammation in multiple peripheral organs.

## Abstract

While the negative effects of sleep deprivation on the brain are well known, the impact on other organs has been less studied. The use of dietary supplements has become increasingly common, even though scientific evidence for their overall health benefits is often limited. Antioxidant supplements may also have side effects and may sometimes act in unexpected ways depending on the biological environment or dose. In this study, we examined the effects of a Cornelian cherry (Cornus mas) fruit extract on several peripheral organs in rats exposed to prolonged REM sleep deprivation. After seven days of sleep loss, the animals showed signs of damage in most examined organs. This included oxidative stress and ultrastructural injury in the liver, oxidative stress in the kidneys, spleen, and aorta, as well as increased levels of inflammatory cytokines in different organs. Treatment with Cornus mas partially protected the liver but had limited effects elsewhere. In the aorta, the extract partly restored some antioxidant parameters but also unexpectedly increased lipid oxidative damage. These findings highlight that the effects of sleep deprivation extend beyond the brain. Furthermore, while based on limited data, extracts with antioxidant properties may prove to be a double-edged sword in some cases.

Supplement use has increased in recent years, despite limited evidence for its broad health benefits. Furthermore, exogenous antioxidants may determine pro-oxidant effects, depending on various factors such as dose, circadian window, and presence of metal ions. Although the effects of sleep deprivation (SD) on the brain are well-documented, its impact on peripheral organs remains relatively underexplored. The goal of this study was to evaluate the effects of a Cornus mas (C. mas) fruit extract on multiple peripheral sites in rats undergoing paradoxical sleep deprivation (PSD). Male Wistar rats were randomly distributed in four groups, including control, C. mas (CM), sleep deprivation (SD), and sleep deprivation and C. mas (SD+CM) (n = 7/group). Seven days of PSD were associated with ultrastructural liver injury and evidence of oxidative dysfunction in several organs: liver, kidney, spleen, and aorta. These alterations were accompanied by marked increases in the evaluated cytokines, including testicular Interleukin-1β, hepatic Interleukin-6, and aortic Interleukin-4. Although the C. mas extract largely maintained hepatic ultrastructure, its effects on other organs were limited. In the aorta, it normalized GSSG values but was also associated with a significant increase in lipid peroxidation. These findings highlight both the systemic impact of SD and caution against assuming uniform benefits of exogenous antioxidants across organ systems in this context.