Abstract
Sleep disorders significantly impact physical health and quality of life. However, the current treatment strategies have several limitations. Panax ginseng has been traditionally employed to calm the mind, but its active components and their mechanisms remain elusive. This study aimed to elucidate the sleep-improving actions of Panax ginseng active component, ginseng Rc, and its potential mechanisms. Sleep duration and rhythm of Drosophila were assessed via a behavior analysis system. Furthermore, the potential addictive side effects of ginsenoside Rc were assessed through capillary ingestion. Changes in mRNA levels of core clock genes and stress response-related genes were determined via RT-qPCR. In addition, the potential mechanisms underlying the efficacy of ginsenoside Rc were evaluated by transcriptomic methodologies. A molecular operating environment (MOE)-Dock simulation was conducted to predict the binding affinity between Pink1 and ginsenoside Rc and verified by surface plasmon resonance. Lastly, Western blotting was carried out to assess Sir2 expression and acetylation of brain proteins. It was observed that ginsenoside Rc improved sleep duration, latency, fragmentation, and amplitude. Furthermore, it upregulated the expression of the clock gene and was not addictive or dependency-inducing. Moreover, it increased antioxidant-related gene expression and reduced stress-related gene expression. In addition, transcriptomic analysis demonstrated that ginsenoside Rc also upregulated autophagy-related genes. Mechanistic studies showed that it improves sleep homeostasis by activating the Pink1/Sir2 signaling pathway, reducing oxidative stress, and modulating protein acetylation levels. This study identified ginsenoside Rc, a novel compound from ginseng, and revealed that it can maintain sleep homeostasis. Mechanistically, ginsenoside Rc alleviated oxidative stress by targeting Pink1 and Sir2. These findings provide evidence for the potential clinical application of ginsenoside Rc for treating sleep disorders.
