Xiaojie Liu1, Fuxiao Wei2, Huanle Liu2, Sijun Zhao3, Guanhua Du4, Xuemei Qin5. 1. Modern Research Center for Traditional Chinese Medicine, Shanxi University, Taiyuan, 030006, Shanxi, China; Shanxi Key Laboratory of Active Constituents Research and Utilization of TCM, Taiyuan, 030006, Shanxi, China. Electronic address: liuxiaojie@sxu.edu.cn. 2. Modern Research Center for Traditional Chinese Medicine, Shanxi University, Taiyuan, 030006, Shanxi, China; Shanxi Key Laboratory of Active Constituents Research and Utilization of TCM, Taiyuan, 030006, Shanxi, China. 3. Modern Research Center for Traditional Chinese Medicine, Shanxi University, Taiyuan, 030006, Shanxi, China; Shanxi Key Laboratory of Active Constituents Research and Utilization of TCM, Taiyuan, 030006, Shanxi, China; Shanxi Institute for Food and Drug Control, Taiyuan, 030001, Shanxi, China. 4. Beijing Key Laboratory of Drug Target and Screening Research, Institute of Materia Medica, Chinese Academy of Medical Sciences, Beijing, 100050, China. 5. Modern Research Center for Traditional Chinese Medicine, Shanxi University, Taiyuan, 030006, Shanxi, China; Shanxi Key Laboratory of Active Constituents Research and Utilization of TCM, Taiyuan, 030006, Shanxi, China. Electronic address: qinxm@sxu.edu.cn.
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE: Xiaoyaosan (XYS), a classic description, has a history of thousands of years for treating depression through invigorating the liver and strengthening the spleen, which have been verified both clinically and experimentally. However, explanation of its underlying mechanisms remains a great challenge. AIM OF THE STUDY: The mechanisms of XYS in treating depression were investigated, with emphasis on the important biomarkers, targets and pathways. MATERIALS AND METHODS: In this study, taking the targeted organ of depression, hippocampus, as the object, a combination of GC-MS based metabolomics and network pharmacology was established to illustrate the abnormality of metabolic characteristics of hippocampus of depression rats and to demonstrate the antidepressant mechanisms of XYS. Hippocampal metabolomics demonstrated potential metabolites involving in the antidepressant effects of XYS, as well as the corresponding metabolic pathways. Network pharmacology screened the potential ingredients and the targets of XYS against depression. RESULTS: Metabolomics revealed that XYS significantly regulated the abnormal levels of lactic acid, glycerol, glutamine, glutamic acid, hypoxanthine, myo-inositol and cholesterol, which involved in the D-glutamine and D-glutamate metabolism, arginine biosynthesis and alanine, aspartate and glutamate metabolism. Network pharmacology showed that XYS exhibited anti-depression effects through paeoniflorin, quercetin, licochalcone a, naringenin, β-sitosterol, formononetin and kaempferol acting on interleukin-6 (IL6), mitogen-activated protein kinase 1 (MAPK1), signal transducer and activator of transcription 3 (STAT3) and transcription factor AP-1 (JUN). CONCLUSION: Based on hippocampal metabolomics and network pharmacology, this study proved that the actions of XYS in treating depression depend on multi-components, multi-targets and multi-pathways, the unique characteristics of TCMs.
ETHNOPHARMACOLOGICAL RELEVANCE: Xiaoyaosan (XYS), a classic description, has a history of thousands of years for treating depression through invigorating the liver and strengthening the spleen, which have been verified both clinically and experimentally. However, explanation of its underlying mechanisms remains a great challenge. AIM OF THE STUDY: The mechanisms of XYS in treating depression were investigated, with emphasis on the important biomarkers, targets and pathways. MATERIALS AND METHODS: In this study, taking the targeted organ of depression, hippocampus, as the object, a combination of GC-MS based metabolomics and network pharmacology was established to illustrate the abnormality of metabolic characteristics of hippocampus of depressionrats and to demonstrate the antidepressant mechanisms of XYS. Hippocampal metabolomics demonstrated potential metabolites involving in the antidepressant effects of XYS, as well as the corresponding metabolic pathways. Network pharmacology screened the potential ingredients and the targets of XYS against depression. RESULTS: Metabolomics revealed that XYS significantly regulated the abnormal levels of lactic acid, glycerol, glutamine, glutamic acid, hypoxanthine, myo-inositol and cholesterol, which involved in the D-glutamine and D-glutamate metabolism, arginine biosynthesis and alanine, aspartate and glutamate metabolism. Network pharmacology showed that XYS exhibited anti-depression effects through paeoniflorin, quercetin, licochalcone a, naringenin, β-sitosterol, formononetin and kaempferol acting on interleukin-6 (IL6), mitogen-activated protein kinase 1 (MAPK1), signal transducer and activator of transcription 3 (STAT3) and transcription factor AP-1 (JUN). CONCLUSION: Based on hippocampal metabolomics and network pharmacology, this study proved that the actions of XYS in treating depression depend on multi-components, multi-targets and multi-pathways, the unique characteristics of TCMs.