Mechanism of Xiaoyao San in treating non-alcoholic fatty liver disease with liver depression and spleen deficiency: based on bioinformatics, metabolomics and in vivo experiments.

Xiaoyao san (XYS) plays an important role in treatment of non-alcoholic fatty liver disease (NAFLD) with liver stagnation and spleen deficiency, but its specific mechanism is still unclear. This study aimed to investigate the material basis and mechanism by means of network pharmacology, metabolomics, systems biology and molecular docking methods. On this basis, NAFLD rat model with liver stagnation and spleen deficiency was constructed and XYS was used to intervene, and liver histopathology, biochemical detection, enzyme-linked immunosorbent assay, quantitative PCR assay and western blotting were used to further verify the mechanism. Through the above research methods, network pharmacology study showed that there were 94 targets in total for XYS in the treatment of NAFLD. Metabolomics study showed that NAFLD with liver depression and spleen deficiency had a total of 73 differential metabolites. Systems biology found that PTGS2 and PPARG were the core targets; Quercetin, kaempferol, naringenin, beta-sitosterol and stigmasterol were the core active components; AA, cAMP were the core metabolites. And molecular docking showed that the core active components can act well on the key targets. Animal experiments showed that XYS could improve liver histopathology, increase 5HT and NA, decrease INS and FBG, improve blood lipids and liver function, decrease AA, increase cAMP, down-regulate PTGS2, up-regulate PPARG, and decrease PGE2 and 15d-PGJ2. In conclusion, XYS might treat NAFLD with liver depression and spleen deficiency by down-regulating PTGS2, up-regulating PPARG, reducing AA content, increasing cAMP, improving insulin resistance, affecting glucose and lipid metabolism, inhibiting oxidative stress and inflammatory response.Communicated by Ramaswamy H. Sarma.

Network pharmacological results found that XYS might treat NAFLD through multiple targets and multiple pathways. Quercetin and kaempferol were main components of XYS in treatment of NAFLD.System biology research results found that PPARG and PTGS2 were the core targets of XYS in the treatment of NAFLD.Metabolomic results suggest that AA and cAMP were differential metabolites of NAFLD.In vivo animal experiments showed that XYS might treat NAFLD by increasing PPARG and decreasing PTGS2, reducing AA and increasing cAMP to regulate glucose metabolism and lipid metabolism.

[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.

Mechanism of Xiaoyao San in treatment of depression,breast hyperplasia,and functional dyspepsia based on network pharmacology / 中国中药杂志

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.