Abstract
Background Although the traditional Chinese medicine Shan-Zhu-Yu may be efficacious against depression, its mechanism of action is unknown. In this study, we aimed to explore the possible mechanisms of action of Shan-Zhu-Yu in the treatment of depression using network pharmacology. Methods The active ingredients and targets of Shan-Zhu-Yu were obtained from the Traditional Chinese Medicine System Pharmacology Database (TCMSP) database and converted into gene names using UniProt. Then, the target genes of depression were collected using GeneCards and OMIM. Drug disease intersection genes were obtained using a Venn tool, and a protein-protein interaction network was constructed using STRING. Cytoscape was used to construct an active ingredients-targets-drug-disease network. GO and KEGG pathway enrichment analyses were performed using DAVID. Furthermore, Autodock was used to evaluate drug and target binding and explore possible molecular mechanisms. Results We identified 9721 disease genes, 13 active ingredients, 50 target genes, and 48 drug disease intersecting genes. The results of the GO enrichment analysis suggested that Shan-Zhu-Yu affects the activity of G protein-coupled amine, neurotransmitter, steroid hormone, nuclear, and G protein-coupled neurotransmitter receptors in the treatment of depression by acting on hormone and nuclear receptor binding. The main signaling pathways were associated with neuroactive ligand-receptor interaction, calcium, cGMP-PKG, apoptosis, estrogen, p53, and AGE-RAGE. Molecular docking confirmed that the active components of Shan-Zhu-Yu (e.g., telocinobufagin and β-sitosterol) docked suitably with NR3C1, Bax, Bcl-2, and caspase-3. Shan-Zhu-Yu may exert its therapeutic effects on depression via multiple targets and pathways. Conclusions The present study elucidates that Shan-Zhu-Yu suppresses the expression of Bax and caspase-3 and promotes that of NR3C1 and Bcl-2 through neuroactive ligand-receptor interaction and apoptosis signaling pathways. Therefore, Shan-Zhu-Yu is a potential treatment option for depression, and the results of this study will provide new reference points for future experimental research and a scientific basis for its widespread clinical application.
Highlights
Depression, a mood or affective mental disorder characterized by anxiety or depressive behaviors, can be caused by various factors. e main symptoms of depression include permanent low spirit, mental retardation, physical discomfort, decreased volitional activity, and cognitive impairment, and the main clinical manifestations are low mood, lack of pleasure, decreased self-worth, and even suicidal thoughts [1]
Evidence-Based Complementary and Alternative Medicine showed that unipolar major depression accounted for 3.7% of disability-adjusted life years (DALYs) in 1990, ranking the fourth, and predicted this to be up to 5.7% in 2020
oral bioavailability (OB), which is a measure of the pharmacokinetic process and druggability in vivo, and DL, which represents the similarity between unknown components and the known chemical structure of drugs, are important parameters to analyze the effectiveness of traditional Chinese medicine [21]. e study combined OB ≥30% and DL ≥0.18 and identified 13 active ingredients (Figure 1(a))
Summary
Depression, a mood or affective mental disorder characterized by anxiety or depressive behaviors, can be caused by various factors. e main symptoms of depression include permanent low spirit, mental retardation, physical discomfort, decreased volitional activity, and cognitive impairment, and the main clinical manifestations are low mood, lack of pleasure, decreased self-worth, and even suicidal thoughts [1]. E antidepressants developed based on this theory include selective serotonin reuptake inhibitors and serotonin and norepinephrine reuptake inhibitors These drugs are tolerated and cause only mild side effects, they have a single-target and slow onset [8]. We aimed to explore the possible mechanisms of action of Shan-Zhu-Yu in the treatment of depression using network pharmacology. E results of the GO enrichment analysis suggested that Shan-Zhu-Yu affects the activity of G protein-coupled amine, neurotransmitter, steroid hormone, nuclear, and G protein-coupled neurotransmitter receptors in the treatment of depression by acting on hormone and nuclear receptor binding. E present study elucidates that Shan-Zhu-Yu suppresses the expression of Bax and caspase-3 and promotes that of NR3C1 and Bcl-2 through neuroactive ligand-receptor interaction and apoptosis signaling pathways. Conclusions. e present study elucidates that Shan-Zhu-Yu suppresses the expression of Bax and caspase-3 and promotes that of NR3C1 and Bcl-2 through neuroactive ligand-receptor interaction and apoptosis signaling pathways. erefore, Shan-Zhu-Yu is a potential treatment option for depression, and the results of this study will provide new reference points for future experimental research and a scientific basis for its widespread clinical application
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