Ghrelin, a brain-gut peptide that induces anxiety and other abnormal emotions, contributes to the effects of insomnia on emotional behavior. In contrast, the traditional Chinese Medicine remedy Wen Dan Tang reduces insomnia-related anxiety, which may perhaps correspond to changes in the brain-gut axis. This suggests a possible relationship between Wen Dan Tang's pharmacological mechanism and the brain-gut axis. Based on this hypothesis, a sleep-deprived rat model was induced and Wen Dan Tang was administered using oral gavage during model establishment. Wen Dan Tang significantly reduced insomnia-related anxiety and prevented Ghrelin level decreases following sleep deprivation, especially in the hypothalamus. Increased expression of Ghrelin receptor mRNA in the hypothalamus was also observed, suggesting that reduced anxiety may be a result of Wen Dan Tang's regulation of Ghrelin-Ghrelin receptors.

Chinese medicine xiangshaliujunzi decoction (XSLJZD) plays a key role in treating functional dyspepsia (FD), a common clinical gastrointestinal disorder. However, the mechanism of this disease is unclear. Brain–gut axis regulates food intake behaviour, and this regulatory mechanism is mediated by neuropeptides. Brain–gut axis impairment and neuropeptide alteration may be the pathological mechanisms of FD, and brain–gut axis regulation may influence the action of medicine. In our experiment, the effect of XSLJZD on FD was evaluated in terms of food intake, sucrose preference test and electromyogram. Changes in neuropeptides [ghrelin, cholecystokinin (CCK) and vasoactive intestinal polypeptide (VIP)] were detected through immunohistochemistry, real-time PCR and ELISA. XSLJZD increased food intake and the percentage of sucrose preference (>75 %). However, the response to gastric detention decreased. Furthermore, XSLJZD increased ghrelin, CCK, VIP proteins and genes in the stomach. XSLJZD also increased ghrelin, CCK and VIP proteins in serum. By contrast, XSLJZD decreased the mRNA expression of these neuropeptides in the hypothalamus. XSLJZD alleviated the symptoms of FD by upregulating the production of ghrelin, CCK and VIP and by increasing the levels of these neuropeptides in circulation. This finding can help elucidate the mechanism of FD and can provide further insight into the pharmacokinetics of XSLJZD.

In recent years, the incidence of fatigue has been increasing, and the effective prevention and treatment of fatigue has become an urgent problem. As a result, the genetic research of fatigue has become a hot spot. Transcriptome-level regulation is the key link in the gene regulatory network. The transcriptome includes messenger RNAs (mRNAs) and noncoding RNAs (ncRNAs). MRNAs are common research targets in gene expression profiling. Noncoding RNAs, including miRNAs, lncRNAs, circRNAs and so on, have been developed rapidly. Studies have shown that miRNAs are closely related to the occurrence and development of fatigue. MiRNAs can regulate the immune inflammatory reaction in the central nervous system (CNS), regulate the transmission of nerve impulses and gene expression, regulate brain development and brain function, and participate in the occurrence and development of fatigue by regulating mitochondrial function and energy metabolism. LncRNAs can regulate dopaminergic neurons to participate in the occurrence and development of fatigue. This has certain value in the diagnosis of chronic fatigue syndrome (CFS). CircRNAs can participate in the occurrence and development of fatigue by regulating the NF-κB pathway, TNF-α and IL-1β. The ceRNA hypothesis posits that in addition to the function of miRNAs in unidirectional regulation, mRNAs, lncRNAs and circRNAs can regulate gene expression by competitive binding with miRNAs, forming a ceRNA regulatory network with miRNAs. Therefore, we suggest that the miRNA-centered ceRNA regulatory network is closely related to fatigue. At present, there are few studies on fatigue-related ncRNA genes, and most of these limited studies are on miRNAs in ncRNAs. However, there are a few studies on the relationship between lncRNAs, cirRNAs and fatigue. Less research is available on the pathogenesis of fatigue based on the ceRNA regulatory network. Therefore, exploring the complex mechanism of fatigue based on the ceRNA regulatory network is of great significance. In this review, we summarize the relationship between miRNAs, lncRNAs and circRNAs in ncRNAs and fatigue, and focus on exploring the regulatory role of the miRNA-centered ceRNA regulatory network in the occurrence and development of fatigue, in order to gain a comprehensive, in-depth and new understanding of the essence of the fatigue gene regulatory network.

In recent years, the World Health Organization (WHO) has included fatigue as a major risk factor for human life and health. The incidence rate of fatigue is high. In Europe and America, nearly 1/3 of the population is suffering from fatigue. Due to the acceleration of modern people’s life rhythm and the increase of work pressure, more and more attention has been paid to central fatigue. The activation of NF-κB is related to central fatigue, which has been paid little attention by previous studies. At the same time, previous studies have mostly focused on the immune regulation function of NF-κB, while the NF-κB pathway plays an equally important role in regulating nerve function. NF-κB can participate in the occurrence and development of central fatigue by mediating immune inflammatory response, regulating central excitability and inhibitory transmitters, regulating synaptic plasticity and regulating central nervous system (CNS) functional genes. In addition to neuroprotective effects, NF-κB also has nerve damage effects, which is also closely related to the occurrence and development of central fatigue. In this review, we focus on the relationship between NF-κB pathway and central fatigue and further explore the biological mechanism of central fatigue. At the same time, the clinical application and potential of typical NF-κB inhibitors in the treatment of fatigue were analyzed to provide reference for the clinical treatment of central fatigue.

Objective. To study the effect of the essential oils of Citrus sinensis L., Mentha piperita L., Syzygium aromaticum L., and Rosmarinus officinalis L. on physical exhaustion in rats. Methods. Forty‐eight male Wistar rats were randomly divided into a control group, a fatigue group, an essential oil mixture (EOM) group, and a peppermint essential oil (PEO) group. Loaded swimming to exhaustion was used as the rat fatigue model. Two groups were nebulized with EOM and PEO after swimming, and the others were nebulized with distilled water. After continuous inhalation for 3 days, the swimming time, blood glucose, blood lactic acid (BLA), blood urea nitrogen (BUN), superoxide dismutase (SOD), glutathione peroxidase (GSH‐PX), and malondialdehyde (MDA) in blood were determined. Results. While an increased time to exhaustion and SOD activity were apparent in both the EOM and PEO groups, the BLA and MDA were lower in both groups, in comparison with the fatigue group, and the changes in the EOM group were more dramatic. Additionally, the EOM group also showed marked changes of the rise of blood glucose and the decrease of BUN and GSH‐PX. Conclusion. The results suggested that the inhalation of an essential oil mixture could powerfully relieve exercise‐induced fatigue.