PURPOSE: To explore the underlying mechanism of AP in exerting anti-fatigue effects.
METHODS: In this study, we developed a chronic sleep deprivation-induced fatigue model and used physiological, hematological, and biochemical indicators to evaluate the anti- fatigue efficacy of AP. Additionally, a multi-omics approach was employed to reveal the anti-fatigue mechanisms of AP from the perspective of microbiome, metabolome, and proteome.
RESULTS: The detection of physiology, hematology and biochemistry index indicated that AP markedly alleviate mice fatigue state induced by sleep deprivation. The 16S rRNA sequencing showed the AP promoted the abundance of probiotics (Odoribacter, Dubosiella, Marvinbryantia, and Eubacterium) and suppressed harmful bacteria (Ruminococcus). On the other hand, AP was found to regulate the expression of colonic proteins, such as increases of adenosine triphosphate (ATP) synthesis and mitochondrial function related proteins, including ATP5A1, ATP5O, ATP5L, ATP5H, NDUFA, NDUFB, NDUFS, and NDUFV. Serum metabolomic analysis revealed AP upregulated the levels of anti-fatigue amino acids, such as taurine, leucine, arginine, glutamine, lysine, and l-proline. Hepatic proteins express levels, especially tricarboxylic acid (TCA) cycle (CS, SDHB, MDH2, and DLST) and redox-related proteins (SOD1, SOD2, GPX4, and PRDX3), were significantly recovered by AP administration. Spearman correlation analysis uncovered the strong correlation between microbiome, metabolome and proteome, suggesting the anti-fatigue effects of AP is attribute to the energy homeostasis and redox balance through gut-liver axis.
CONCLUSION: AP increased colonic ATP production and improve mitochondrial function by regulating gut microbiota, and further upregulated anti-fatigue amino acid levels in the blood. Based on the gut-liver axis, AP upregulated the hepatic tricarboxylic acid cycle and oxidoreductase-related protein expression, regulating energy homeostasis and redox balance, and ultimately exerting anti-fatigue effects. This study provides insights into the anti-fatigue mechanisms of AP, highlighting its potential as a therapeutic agent.
METHODS: A prospective cross-sectional study was performed among young doctors less than 40 years old, working at King Chulalongkorn Memorial Hospital, Bangkok, Thailand, and Hospital Kuala Lumpur, Kuala Lumpur, Malaysia, using questionnaires and home sleep apnea testing (Apnealink™Plus). The primary objective of this study was to evaluate the prevalence of OSA (apnea-hypopnea index (AHI) ≥5). The secondary objectives were to evaluate the prevalence of obstructive sleep apnea syndrome (OSAS) defined by AHI ≥5 + excessive daytime sleepiness (EDS), sleep deprivation (the difference of weekend (non-workdays) and weekday (workdays) wake-up time of at least 2 h), EDS (Epworth Sleepiness Scale score ≥10), tiredness, and perception of inadequate sleep as well as to identify their predictors.
RESULTS: Total of 52 subjects completed the study. Mean age and mean body mass index (BMI) were 31.3 ± 4 and 23.3 ± 3.6, respectively. The prevalence of OSA and OSAS were 40.4 and 5.8 %, respectively. One third of OSA subjects were at least moderate OSA. Prevalence of sleep deprivation, EDS, tiredness, and perception of inadequate sleep were 44.2, 15.4, 65.4, and 61.5 %, respectively. History of snoring, being male, and perception of inadequate sleep were significant predictors for OSA with the odds ratio of 34.5 (p = 0.016, 95 % CI = 1.92-619.15), 18.8 (p = 0.001, 95 % CI = 3.10-113.41), and 7.4 (p = 0.037, 95 % CI = 1.13-48.30), respectively. Only observed apnea was a significant predictor for OSAS with odds ratio of 30.7 (p = 0.012, 95 % CI = 2.12-442.6). Number of naps per week was a significant predictor for EDS with the odds ratio of 1.78 (p = 0.007, 95 % CI = 1.17-2.71). OSA and total number of call days per month were significant predictors for tiredness with the odds ratio of 4.8 (p = 0.036, 95 % CI = 1.11-20.72) and 1.3 (p = 0.050, 95 % CI = 1.0004-1.61), respectively. OSA was the only significant predictor for perception of inadequate sleep with the odd ratios of 4.5 (p = 0.022, 95 % CI = 1.24-16.59).
CONCLUSIONS: Our results demonstrated relatively high prevalence of OSA and OSAS among young doctors. Snoring, being male, and perception of inadequate sleep were significant predictors for OSA. Observed apnea was a significant predictor for OSAS. OSA was a significant predictor for tiredness and perception of inadequate sleep.
ABSTRACT: Oxidative stress-mediated lipid peroxidation is a known cause of endothelial injury or dysfunction. Deprivation of rapid eye movement (REM) sleep is associated with oxidative stress. To date, the pathogenesis of increased blood pressure after sleep deprivation remains poorly understood, particularly in the REM sleep phase. Our aim was to investigate the effects of REM sleep deprivation on blood vessels in the REM sleep-deprived rat model. Twenty-eight male Sprague-Dawley rats were divided into four equal groups: free-moving control rats, rats deprived of REM sleep for 72 h (REMsd), tank control rats and 72 h sleep-recovered rats after 72 h of REM sleep deprivation. The rats were deprived of REM sleep using the inverted flowerpot technique. Food consumption, body weight gain and systolic blood pressure were monitored. At the end of the experiment, the descending thoracic aorta was isolated for the measurement of oxidative stress markers. Despite a significant increase in food consumption in the REMsd group compared with the other groups, there was a significant reduction in body weight gain. Systolic blood pressure also showed a significant increase in the REMsd group compared with the other groups. Superoxide dismutase activity was significantly lower and malondialdehyde concentrations significantly higher in the REMsd group compared with the other groups. Increased levels of malondialdehyde are suggestive of lipid peroxidation in the blood vessels, and oxidative stress may be attributed to the initiation of the process. The changes after REM sleep deprivation revert during sleep recovery. In conclusion, the findings of the present study provide convincing evidence that REM sleep deprivation induced lipid peroxidation, leading to endothelial damage.