Under the current COVID-19 pandemic, many people with depression and insomnia may be related to environmental mutations and social anxiety. The study found that the symptom levels of depression, anxiety and insomnia in the quarantine area were significantly higher than those in the nonquarantine area, and they were at higher risk of depression, anxiety and insomnia, especially the severity of depression . TCM believes that the main pathogenesis of insomnia is the imbalance of Qi and the inability of Yang to enter Yin. The Yellow Emperor’s Internal Classic states, "If you are unable to make decisions, or if your emotions are not smooth, the liver qi will be stagnant, and the qi axis will not turn, but if you want to stretch, you will be inward. Disturb the soul and cause insomnia", and depression is due to stagnation of liver qi, so liver-regulating qi is the basic rule for the treatment of insomnia and depression, suggesting that qi-regulating drugs are potential drugs for the treatment of depression.
CHSGP is composed of 7 herbs: Chaihu, Xiangfu, Chuanxiong, Chenpi, Zhike, Baishao, and Gancao. Saikosaponin, the main chemical component of Chaihu, has sedative, antipyretic, immune enhancement, anti-inflammatory, antiviral, liver, and antitumor effects. The α-germanone of Xiangfu has an antidepressant-like effect , and Jiawei Xiangfu Decoction combined with acupuncture can significantly improve the sleep state of menopausal insomnia patients with liver stagnation and qi stagnation . The main active ingredients of Chuanxiong have both a sedative effect and the potential to improve depression. The antidepressant mechanism of Chenpi and its main active ingredients, chuanchenein, hesperidin and naringenin, is related to the improvement of neurobiochemical, neuroendocrine and neurotrophic systems . Zhike exerts antidepressant effects mainly through its monoaminergic mechanism and prokinetic effects . Fructus aurantii can enhance gastrointestinal motility by changing the expression level of 5-HT in the gastrointestinal tract of rats , suggesting that it can affect sleep to a certain extent. Paeoniflorin has neuroprotective and antidepressant biological activities, and it can treat related insomnia diseases through adenosine A1R to play a hypnotic effect . Regulating the calmodulin/calmodulin-dependent protein kinase II (CaM/CaMKII) pathway and its downstream signaling molecules play an important role in the treatment and alleviation of affective disorders . Glycyrrhizin can reduce IL-6 cytokines in brain tissue, and it is also a cytokine closely related to sleep/deprivation. IL-6 can inhibit the synthesis of IL-1 and reduce IL-6 cytokines, and then IL-1 increases synthesis, which in turn enhances the patient’s nonrapid eye movement sleep time .
The results of the study showed that topological analysis identified the key components of quercetin, kaempferol, β-sitosterol, 7-methoxy-2-methyl isoflavones, luteolin, naringenin and other key components in CHSGP as the disease. It was the material basis for the treatment of insomnia and depression with the same treatment of different diseases. It had the largest number of targets and was also its core compound. Studies have shown that quercetin enhanced the hypnotic activity of pentobarbital in a dose-dependent manner by prolonging sleep time  and reducing anxiety and depression-like behaviors, immune dysfunction and brain oxidative stress , related to its improvement of neurotrophic function and anti-inflammatory effects. Kaempferol has a wide range of pharmacological activities, which can reduce oxidative stress and proinflammatory cytokines, inhibit vascular endothelial inflammation , and have an effective antidepressant effect [26, 43]. Studies have found  that some Chinese herbal extracts contain β-sitosterol, which has anti-inflammatory, sedative and hypnotic activities . Luteolin is a widely used flavonoid compound that has anti-anxiety and sleep-promoting effects . Naringenin can activate Sirt1, enhance antioxidant capacity by reducing oxidative stress, and effectively improve inflammation and dopamine levels , thereby alleviating the pain caused by chronic sleep deprivation .
According to the drug-disease target intersection, CHSGP can treat insomnia and depression at the same time through 113 target proteins in different diseases. According to the degree value and the betweenness centrality, PPI analysis network topology analysis screened AKT1 and IL-6, and 42 core targets, such as IL1B, CASP3, and MAPK3, were mainly related to immunity, inflammation, oxidative stress, and neovascularization. AKT1 is involved in the regulation of processes such as metabolism, proliferation, growth and angiogenesis . IL-6 is one of the most biologically active cytokines and can be called a sleepy mediator. Its circadian rhythm pattern reflects the steady-state drive of sleep , and increased IL-6 activity may cause depression by activating the hypothalamus-pituitary-adrenal axis or affecting neurotransmitter metabolism . IL-1B protein is an important mediator of the inflammatory response, is involved in a variety of cell activities, such as cell proliferation, differentiation, and apoptosis, and is related to the diagnosis, specific symptoms, and antidepressant treatment response of major depression . Caspase-3 (CASP3) belongs to the cysteine aspartic protease (Caspase) family of proteases and plays an irreplaceable role in the apoptosis pathway. Hippocampal apoptosis caused by sleep deprivation includes the number of apoptotic cells, caspase-3 activation, and Bax and Bcl-2 regulation. MAPK3, called mitogen-activated protein kinase 3, is an important part of the MAP kinase signal transduction pathway and plays an important role in the cellular response cascade caused by extracellular stimulation. Another study showed that the expression of the AKT1, MAPK3 and IL-6 genes in anxiety patients often increased significantly. The MCODE cluster analysis in the PPI network screened 7 core genes, including FOS, GABRA2, GSK3B, PON1, APOB, CYP1B1, and ADRA1A. FOS, also known as c-Fos, is a proto-oncogene that participates in cell growth, differentiation, information transmission, animal learning and memory and maintains wakefulness. Studies have shown that  FOS protein is involved in the normal differentiation, growth, learning, memory and other processes of cells, and it is more highly expressed in the brain endothelium, hippocampus, and striatum. GABA is found only in the nervous tissues of animals. It is an important inhibitory neurotransmitter and plays a role in the development process. It participates in a variety of metabolic activities and has high physiological activity. The GABRA2 gene encodes the GABAA-2 subunit, which is an ionotropic receptor related to anxiety, depression, and other behavioral disorders (including drug dependence and schizophrenia). Studies have found that a higher expression level of α2 may have antidepressant effects through the signal transduction of GABAAR containing α2.
PPI network and GO analysis showed that the strong interactions of these target genes affected the synaptic membrane and postsynaptic membrane by participating in biological processes such as drug response, regulation of blood vessel diameter, and oxidative stress response, which included the molecular functions of synaptic membrane, postsynaptic membrane and its components, and which involved cell functions such as neurotransmitter receptor activity, postsynaptic neurotransmitter receptor activity, G protein coupled amine receptor activity, etc. The KEGG pathway enrichment analysis mainly involved the AGE-RAGE signaling pathway, neuroactive ligand–receptor interaction, IL-17 signaling pathway, TNF signaling pathway, endocrine resistance, Th17 cell differentiation, dopaminergic synapses, hepatitis B, Toll-like receptor signaling pathways and other signaling pathways related to inflammation, immunity, and oxidative stress.
Studies have found that the inhibition of the AGE/RAGE pathway and oxidative stress might be a possible mechanism by which melatonin exerts antidepressant and anti-anxiety effects in diabetic rats. AGE-RAGE signaling is among the signaling pathways related to obstructive sleep apnea (OSA). A number of network pharmacology studies have found that TCM has neuroactive ligand–receptor interaction pathways in the treatment of depression or insomnia [16, 58–60]. A literature study found that it might have a beneficial effect on the pathogenic conditions of the central nervous system by inhibiting the function of the IL-17 cytokine family .
The molecular docking results showed that the molecular docking in compounds (kaempferol, luteolin, quercetin, 7-methoxy-2-methyl isoflavone and beta-sitosterol) and five target proteins (AKT1, IL1B, IL-6, FOS, GSK3B, and GABRA) matched well, and the binding energy was less than − 6 kcal/mol, which could form stable complexes and indirectly verified that these compounds had a regulatory effect on targets such as AKT1.
This study is aimed at the high incidence of global depression and insomnia under the current situation of the COVID-19 epidemic, and it is difficult to find effective prevention methods in clinical practice. At the same time, the network pharmacology of CHSGP provides us with an opportunity to explore the “Same Treatment for Different Diseases” potential pharmacological mechanism of CHSGP in treating insomnia and depression caused by the COVID-19 epidemic. Existing network pharmacology studies have screened 121 active ingredients and 15 depression-related targets of CHSGP from the database, mainly involving the regulation of neurotransmitters (serotonin, dopamine and adrenaline), the regulation of inflammatory mediators of TRP channels, calcium signaling pathway, cyclic adenosine monophosphate signaling pathway, and neural active ligand–receptor interaction, which are the channels through which signals play an antidepressant effect. It can have an antidepressant effect by improving neuronal plasticity, growth, transfer conditions and gene expression in neuronal cells and increasing the expression of gap junction proteins . Animal experiments  confirmed that CHSGP can improve the depression-like behavior of rats exposed to chronic unpredictable mild stress (CUMS), possibly by inhibiting CHOP and caspase-12-mediated apoptosis of rat hippocampal cells. CHSGP can significantly improve the depression state of model rats by increasing the expression of BDNF and TrkB mRNA in the hippocampus, amygdala and frontal lobe . A large number of clinical studies [64–66] have shown that CHSGP alone or combined with Western medicine has a significant effect on the treatment of insomnia, and network pharmacology data mining CHSGP may play a role in the treatment of insomnia through multiple components, multiple targets, and multiple pathways .
Although the research has some findings, it still has many limitations. First, due to incomplete information, the role of some CHSGP compounds in “Same Treatment for Different Diseases” may be ignored. Second, it is difficult to screen specific targets and key active ingredients directly from the complex cognitive CHSGP. Third, although CHSGP has antidepressant and sleep-improving effects in previous clinical studies and animal model experiments, its mechanism of action is still unclear, and further analysis and excavation are needed in subsequent clinical and animal experiments. Therefore, it is necessary to further study the role and specific targets and pathways of the important single components of the CHSGP in the process of treating insomnia and depression with the “Same Treatment for Different Diseases”.