[Mechanism of Xiaoyao San in treatment of depression,breast hyperplasia,and functional dyspepsia based on network pharmacology].

This study aimed to explore the mechanism of Xiaoyao San(XYS) in the treatment of three diseases of liver depression and spleen deficiency, ie, depression, breast hyperplasia, and functional dyspepsia, and to provide a theoretical basis for the interpretation of the scientific connotation of "treating different diseases with the same method" of traditional Chinese medicines. Traditional Chinese medicine systems pharmacology database and analysis platform(TCMSP) was used to screen the active components of XYS which underwent principal component analysis(PCA) with the available drugs for these three diseases to determine the corresponding biological activities. The targets of XYS on depression, breast hyperplasia, and functional dyspepsia were obtained from GeneCards, TTD, CTD, and DrugBank databases. Cytoscape was used to plot the "individual herbal medicine-active components-potential targets" network. The resulting key targets were subjected to Kyoto encyclopedia of genes and genomes(KEGG) pathway analysis and gene ontology(GO) enrichment analysis. A total of 121 active components of XYS and 38 common targets in the treatment of depression, breast hyperplasia, and functional dyspepsia were collected. The key biological pathways were identified, including advanced glycation and products(AGEs)-receptor for advanced glycation and products(RAGE) signaling pathway in diabetic complications, HIF-1 signaling pathway, and cancer-related pathways. The key targets of XYS in the treatment of depression, breast hyperplasia, and functional dyspepsia included IL6, IL4, and TNF, and the key components were kaempferol, quercetin, aloe-emodin, etc. As revealed by the molecular docking, a strong affinity was observed between the key components and the key targets, which confirmed the results. The therapeutic efficacy of XYS in the treatment of diseases of liver depression and spleen deficiency was presumedly achieved by reducing the inflammatory reactions. The current findings are expected to provide novel research ideas and approaches to classify the scientific connotation of "treating different diseases with the same method" of Chinese medicines, as well as a theoretical basis for understanding the mechanism of XYS and exploring its clinical applications.

[Research progress in combination applications of antidepressant drugs].

Depression is a common affective disorder. The application of antidepressants can significantly alleviate the symptoms of depression, which is the most important way to treat depression in clinical practice. Due to the complex etiology, wide variety, as well as diversity and severity of serious concomitant symptoms, rational addition of other drugs into antidepressants can significantly improve the cure rates of depression, reduce adverse reactions, and improve patient compliances. Therefore, the combined applications of differential drugs have been commonly used in clinic. In this paper, more than 600 literatures about depression from 2010 to 2019 were collected based on the key words of antidepressant, depression, combined medication, synergism and increase efficiency. Based on this, by summarizing and classifying the existing combinations of antidepressant drugs, this paper systematically expounds the current combined applications of antidepressant drugs in three categories, i.e. western medicines combined with western medicines, western medicines combined with traditional Chinese medicines, and traditional Chinese medicines combined with traditional Chinese medicines, in the expectation of providing the direction and basis for the selection of rational combinations of antidepressant drugs in clinic.

The synergistic anti-depression effects of different efficacy groups of Xiaoyaosan as demonstrated by the integration of network pharmacology and serum metabolomics.

Compatibility investigations are vital but also the most difficult aspect of traditional Chinese medicine (TCM) prescriptions. Previous researches have demonstrated that Xiaoyaosan (XYS) is an effective treatment for depression. However, the compatibility rules of XYS and the underlying mechanisms remain unclear. Herein, we combined network pharmacology and serum metabolomics to investigate the scientific connotations and the compatibility effects of XYS. First, the Traditional Chinese Medicine Systems Pharmacology (TCMSP) and the GeneCards databases were applied to identify the chemical components and the putative targets of XYS, and its efficacy groups. We then analyzed the herb-component-target pathways and constructed PPI networks. Potential pathways were determined by gene ontology (GO) and pathway enrichment analyses. Additionally, a chronic unpredictable mild stress (CUMS) model was applied on rats. A proton nuclear magnetic resonance spectrometry (1H NMR) based serum metabolomics was then used to identify potential metabolites and the corresponding pathways that were involved in depression and the potential anti-depression effects of XYS and its efficacy groups. A total of 121 components of XYS and 111 targets were associated with depression. Additionally, we screened 105 targets of 24 components in Shugan (SG) group and 106 targets of 95 components in Jianpi (JP) group. 13 targets were common to all three groups. Protein-protein interaction network analysis showed that Caspase-3 and Nitric oxide synthase-3 were nodes that overlapped with proteins known to be associated with depression. Pathway enrichment analysis further indicated that the putative targets of XYS and its efficacy groups mostly participated in pathways associated with cancer. Also, XYS and its efficacy groups significantly reversed abnormalities of serum metabolites and metabolic pathways, but to different degrees. Overall, different efficacy groups of XYS exhibit synergistic anti-depression effects and contribute to the whole prescription against depression. This study shows that the combination of network pharmacology and metabolomics is an effective approach to demonstrate scientific connotations and compatibility of TCMs from a holistic perspective.

Hepatic metabolomics of the compatibility effect of Xiaoyaosan on CUMS-induced depression based on the TCM theory of "Treating Diseases via Regulating the Liver's Function".

This study aimed to demonstrate the scientific connotations and compatibility effects of Xiaoyaosan (XYS) based on the theory of "Treating Diseases via Regulating the Liver's Function" by hepatic metabolomics. XYS was divided into two efficacy groups, i.e. the Shugan (SG) and the Jianpi (JP) groups, according to the strategy of "Efficacy Compositions". The chronic unpredictable mild stress (CUMS) depression model was constructed. A 1H NMR-based hepatic metabolomics approach coupled with multivariate data (MVD) analysis was performed. Meanwhile, relative distance (RD) and Efficacy Index (EI) were calculated. XYS and its efficacy groups significantly reversed the abnormality of behavior and hepatic metabolomics of depression rats, but to different degrees. The results of ethology and metabolomics showed the same order, i.e. XYS > JP > SG. Two metabolites, i.e. tyrosine and malate, were regulated by all the treatment groups. Four metabolites were significantly regulated only by XYS group. Of note, the results showed the two efficacy groups of XYS exhibited synergistic anti-depression effects, and glutamate, malate and taurine could be the key hepatic metabolites for these synergistic effects. The current study not only complements and consummates the mechanisms of depression and the anti-depression effects of XYS from the perspective of hepatic metabolomics, but also lays a solid foundation for comprehensively and deeply understanding the compatibility effects of XYS against depression, especially from the points of view of compatibility in Traditional Chinese medicine (TCM) theory and synergism in modern medicine theory.