AIM To investigate gut microbial diversity and the interventional effect of Xiaoyaosan(XYS) in a rat model of functional dyspepsia(FD) with liver depression-spleen deficiency syndrome. METHODS The FD with liver depres...AIM To investigate gut microbial diversity and the interventional effect of Xiaoyaosan(XYS) in a rat model of functional dyspepsia(FD) with liver depression-spleen deficiency syndrome. METHODS The FD with liver depression-spleen deficiency syndrome rat model was established through classic chronic mild unpredictable stimulation every day. XYS group rats received XYS 1 h before the stimulation. The models were assessed by parameters including state ofthe rat, weight, sucrose test result and open-field test result. After 3 wk, the stools of rats were collected and genomic DNA was extracted. PCR products of the V4 region of 16 S rD NA were sequenced using a barcoded Illumina paired-end sequencing technique. The primary composition of the microbiome in the stool samples was determined and analyzed by cluster analysis.RESULTS Rat models were successfully established, per data from rat state, weight and open-field test. The microbiomes contained 20 phyla from all samples. Firmicutes, Bacteroidetes, Proteobacteria, Cyanobacteria and Tenericutes were the most abundant taxonomic groups. The relative abundance of Firmicutes, Proteobacteria and Cyanobacteria in the model group was higher than that in the normal group. On the contrary, the relative abundance of Bacteroidetes in the model group was lower than that in the normal group. Upon XYS treatment, the relative abundance of all dysregulated phyla was restored to levels similar to those observed in the normal group. Abundance clustering heat map of phyla corroborated the taxonomic distribution. CONCLUSION The microbiome relative abundance of FD rats with liver depression-spleen deficiency syndrome was significantly different from the normal cohort. XYS intervention may effectively adjust the gut dysbacteriosis in FD.展开更多
Objective:To observe changes in the molecular expression of the NLR Family Pyrin Domain Containing Protein 3(NLRP3)pathway in depressed rats after treatment with Xiaoyaosan,and identify the regulatory mechanism of thi...Objective:To observe changes in the molecular expression of the NLR Family Pyrin Domain Containing Protein 3(NLRP3)pathway in depressed rats after treatment with Xiaoyaosan,and identify the regulatory mechanism of this compound.Methods:Male SpragueeD awley rats were randomly divided into five groups with 12 rats in each group,including the control group,model group,Fluoxetine group,Xiaoyaosan group,and MCC950 group.A depression model was generated by chronic immobilization stress(induced by 3 h of restraint immobilization every day),and the drugs were administered at the same time in each group for 21 days.The effects of Xiaoyaosan on behavioral changes of depressed rats were observed through macroscopic characterization,body mass,open field experiments,and a sucrose preference test.The m RNA and protein expression of the NLRP3 signaling pathway was examined by fluorescence real-time quantitative PCR and Western blot assays.Results:The Xiaoyaosan group,Fluoxetine group,and MCC950 group rats showed improved depressive behavior and an increased weight of sucrose water consumption.The protein and mRNA expression levels of NLRP3,Caspase-1,and IL-1 b were also decreased in the Fluoxetine,Xiaoyaosan,and MCC950 groups.Conclusion:NLRP3,Caspase-1,and IL-1 b protein and mRNA expression levels were increased in the cortex of depressed rats,while Xiaoyaosan protected cortical tissue in these rats by decreasing NLRP3,Caspase-1,and IL-1 b protein and mRNA expression.展开更多
OBJECTIVE Depression is one of the prevalent and prominent complex psychiatric diseases and the number of depressed patients has been on the rise globally during the recent decades.Xiaoyaosan,as a famous Chinese herba...OBJECTIVE Depression is one of the prevalent and prominent complex psychiatric diseases and the number of depressed patients has been on the rise globally during the recent decades.Xiaoyaosan,as a famous Chinese herbal formula,has been widely used in depression patients for a long time. However,the therapeutic mechanisms remain uncertain because of difficulty of depression pathophysiology and the lack of bioinformatic approach to understand the molecular connection. METHODS In this thesis,we applied a network pharmacology approach to explain the potential mechanisms between Xiaoyaosan and depression involved in oral bioavailability screening,drug-likeness assessment,caco-2 permeability,blood-brain barrier target recognition and network analysis. RESULTS 66 active compounds in Xiaoyaosan formula with favorable pharmacokinetic profiles are predicted as active compounds for anti-depression treatment. Network analyses show that these 66 compounds target 40depression-associated proteins including especially HTR2A,NR 3C1,MAOB,XDH and CNR2. These proteins are mainly involved in the neuroactive ligand-receptor interaction,serotonergic synapse,cAMP signaling pathways and calcium signaling pathways. CONCLUSION The integrated network pharmacology method is an effective approach to illustrate the anti-depression mechanisms of herbs,and this in silico approach can be applied in drug discovery.展开更多
in hippocampal neurons is an important contributor to depression. [Ca^2＋]i of hippocampal neurons may raise rapidly with increased corticosterone concentrations, leading to apoptosis. The anti-depressant effects of X...in hippocampal neurons is an important contributor to depression. [Ca^2＋]i of hippocampal neurons may raise rapidly with increased corticosterone concentrations, leading to apoptosis. The anti-depressant effects of Xiaoyaosan （Free and Easy Wanderer＇s Powder） may inhibit apoptosis by down regulating the [Ca^2＋]i overload. PC12 cells were containing with corticosterone to simulate neuronal injury, dosed with Xiaoyaosan-containing serum, and the following parameters were measured： apoptosis,[Ca^2＋]i overload, and changes in mitochondrial membrane potential （△ψm） and bioenergetics. High-dose Xiaoyaosan-containing serum （the dose of intragastric administration was 2.633 g herb/mL） not only inhibited morphological injury and cell apoptosis, but also suppressed [Ca^2＋]i overload induced by corticosterone. Xiaoyaosan also blocked the decrease in mitochondrial membrane potential and adenosine triphosphate levels induced by corticosterone. Xiaoyaosan dose-dependently suppresses corticosterone-induced apoptosis, potentially via inhibiting [Ca^2＋]ioverload, and prevents impaired mitochondrial bioenergetics by maintaining mitochondrial membrane potential and adenosine triphosphate production, providing a putative mechanism for its antidepressant effects.展开更多
The antidepressive effect of Xiaoyaosan is doubtless by researches while the potential antidepressive ac- tive ingredients and their mechanisms remain unclear. In order to explain the antidepressive effect of Xiaoyaos...The antidepressive effect of Xiaoyaosan is doubtless by researches while the potential antidepressive ac- tive ingredients and their mechanisms remain unclear. In order to explain the antidepressive effect of Xiaoyaosan, all of the recent reports were sought out on the current situation of the antidepressive monomer compositions of Xi- aoyaosan and their mechanism. By exploring the relationship between the effects and the active ingredients, the mechanism and the active ingredients, the antidepressive active ingredients such as quercetin, isorhamnetin, isoliquiritigenin, saikosaponinA, saikosaponinD, glycyrrhiz- kaempferol, liquiritin, isoliquiritin, liquiritigenin, inate, paeoniflorin, albiflorin, ferulic acid, curcumin and their mechanism of antidepressive such as regulating the monoamine neurotransmitter systems, regulating the neuroendocrine system, affecting the neural plasticity and neu- affecting the cytokines level, anti-oxidative stress were rotrophic, affecting the cellular and molecular mechanisms , summarized. By the overview in the level of monomer rather than formulae, we uncovered the antidepressive mech- anism of Xiaoyaosan and further confirmed that Xiaoyaosan, as a classic antidepressive Chinese prescription, had many characteristics, such as multi-level , multi-channel, multi-target and so on .展开更多
Aim The study focused on identification and antidepression active verification of constituents from An- gelica Sinensis Radix contrubuting to Xiaoyaosan based on UPLC-PDA guided isolation technique. Methods The UPLC-P...Aim The study focused on identification and antidepression active verification of constituents from An- gelica Sinensis Radix contrubuting to Xiaoyaosan based on UPLC-PDA guided isolation technique. Methods The UPLC-PDA chromatogram of Xiaoyaosan was compared with that of Angelica Sinensis Radix. The relative retention time of each peak and the Uhraviolet spectra providing by PDA were used in the analyses. Constituents were isola- ted from Angelica Sinensis Radix under the guidance of UPLC-PDA investigation. Structures of the isolates were elu- cidated by NMR techniques. Anti-depression effect was evaluated on glutamate-induced neurons. Results Five marker peaks of Xiaoyaosan fingerprint were belong to Angelica Sinensis Radix, and they were determined as conife- ryl ferulate（ I）, E-butylidenephthalide （ II）, ligustilide （III）, Z-butylidenephthalide （ IV ）, 14-Acetoxy-12-sene- cioyloxytetradeca-2E,8E,10E-trien-4,6-diyn-l-ol（V）. Compound V was isolated from the plants of Umbelliferae for the first time. Treatment with compound I, III, IV can protect PC12 and SH-SY5Y cell from glutamate-induced cytotoxicity. Antidepression bioactivity of compound I was first investigated. Conclusion UPLC-PDA guided iso-lation technique was confirmed to be a rapid and accurate method to identify the main active constituents from An- gelica Sinensis Radix contrubuting to Xiaoyaosan.展开更多
The hippocampus is one of the most commonly studied brain regions in the context of depression.The volume of the hippocampus is significantly reduced in patients with depression,which severely disrupts hippocampal neu...The hippocampus is one of the most commonly studied brain regions in the context of depression.The volume of the hippocampus is significantly reduced in patients with depression,which severely disrupts hippocampal neuroplasticity.However,antidepressant therapies that target hippocampal neuroplasticity have not been identified as yet.Chinese medicine(CM)can slow the progression of depression,potentially by modulating hippocampal neuroplasticity.Xiaoyaosan(XYS)is a CM formula that has been clinically used for the treatment of depression.It is known to protect Gan(Liver)and Pi(Spleen)function,and may exert its antidepressant effects by regulating hippocampal neuroplasticity.In this review,we have summarized the association between depression and aberrant hippocampal neuroplasticity.Furthermore,we have discussed the researches published in the last 30 years on the effects of XYS on hippocampal neuroplasticity in order to elucidate the possible mechanisms underlying its therapeutic action against depression.The results of this review can aid future research on XYS for the treatment of depression.展开更多
Depression is one of the most prevalent and serious mental disorders with a significant burden of disease.Xiaoyaosan(XYS),a well-known Chinese formula,has been widely used in the treatment of depression.Both clinical ...Depression is one of the most prevalent and serious mental disorders with a significant burden of disease.Xiaoyaosan(XYS),a well-known Chinese formula,has been widely used in the treatment of depression.Both clinical studies and animal experiments have indicated that XYS has an obvious antidepressant activity.How to select objective pharmacodynamic markers for traditional Chinese medicine(TCM)treatments based on clinical metabolites,linking pathogenic genes,and drug targets,is a bottleneck problem in the modernization of TCM.To address this issue,we sorted out clinical metabonomics experiments of XYS in treating depression,constructed a metabolic profile of therapeutic biomarkers,and deduced metabolic biomarker-protein interactions networks.The therapeutic biomarkers found for XYS were involved in neurotransmitter synthesis,energy metabolism,and gut microbial metabolism.This study aims to provide a scientific basis for the clinical diagnosis of depression and evaluate the efficacy of XYS in its treatment.展开更多
Objective: Depression is one of the prevalent and prominent complex psychiatric diseases, and the number of depressed patients has been on the rise globally during the recent decades.Xiaoyaosan, as a famous Chinese he...Objective: Depression is one of the prevalent and prominent complex psychiatric diseases, and the number of depressed patients has been on the rise globally during the recent decades.Xiaoyaosan, as a famous Chinese herbal formula, has been widely used in depression patients for a long time.However, the therapeutic mechanisms remain uncertain because of the difficulty of depression pathophysiology and the lack of bioinformatic approach to understand the molecular connection.Materials and Methods: In this thesis, we applied a network pharmacology approach to explain the potential mechanisms between Xiaoyaosan and depression involved in oral bioavailability screening, drug-likeness assessment, caco-2 permeability, blood–brain barrier target recognition, and network analysis.Results: Sixty-six active compounds in Xiaoyaosan formula with favorable pharmacokinetic profiles are predicted as active compounds for antidepression treatment.Network analyses showed that these 66 compounds target 40 depression-associated proteins including especially HTR2A, NR3C1, monoamine oxidase inhibitor B, XDH, and CNR2.These proteins are mainly involved in the neuroactive ligand–receptor interaction, serotonergic synapse, cAMP signaling pathways, and calcium signaling pathways.Conclusion: The integrated network pharmacology method can provide a new approach for understanding the pathogenesis of depression and uncovering the molecular mechanisms of Xiaoyansan, which will also facilitate the application of traditional Chinese herbs in modern medicine.展开更多
目的利用液相色谱质谱(liquid chromatography-tandem mass spectrometry,LC-MS)技术进行逍遥散治疗抑郁症的代谢组学实验研究。方法纳入2021年6月—2022年6月在南阳市第四人民医院经逍遥散治疗的36例抑郁症患者作为研究对象,采集患者...目的利用液相色谱质谱(liquid chromatography-tandem mass spectrometry,LC-MS)技术进行逍遥散治疗抑郁症的代谢组学实验研究。方法纳入2021年6月—2022年6月在南阳市第四人民医院经逍遥散治疗的36例抑郁症患者作为研究对象,采集患者的空腹血液样本。采用高效液相色谱(high performance liquid chromatography,HPLC)和质谱联用技术对代谢物样本进行分析,采用逆向相色谱柱进行分离,质谱采用高分辨质谱测量碎片;通过质谱化合物的浓度和碎片图谱特征,得到代谢物的定性和定量结果。结果逍遥散治疗后抑郁症患者血浆代谢轮廓发生了显著改变,在代谢组学谱图中鉴定出19个差异显著的代谢物。逍遥散治疗后抑郁症患者的代谢物谱主要集中在为甘油磷脂代谢、脂肪酸代谢等9种代谢途径。逍遥散治疗后上述代谢组学指标水平趋于正常组。结论通过LC-MS技术,可以有效地鉴定出逍遥散治疗抑郁症的代谢物谱,为进一步的药物研究和临床应用提供了重要的参考依据。展开更多
基金Supported by National Natural Science Foundation of China,No.81273919 and No.81673727National Basic Research Program of China(973 Program)No.2013CB531703
文摘AIM To investigate gut microbial diversity and the interventional effect of Xiaoyaosan(XYS) in a rat model of functional dyspepsia(FD) with liver depression-spleen deficiency syndrome. METHODS The FD with liver depression-spleen deficiency syndrome rat model was established through classic chronic mild unpredictable stimulation every day. XYS group rats received XYS 1 h before the stimulation. The models were assessed by parameters including state ofthe rat, weight, sucrose test result and open-field test result. After 3 wk, the stools of rats were collected and genomic DNA was extracted. PCR products of the V4 region of 16 S rD NA were sequenced using a barcoded Illumina paired-end sequencing technique. The primary composition of the microbiome in the stool samples was determined and analyzed by cluster analysis.RESULTS Rat models were successfully established, per data from rat state, weight and open-field test. The microbiomes contained 20 phyla from all samples. Firmicutes, Bacteroidetes, Proteobacteria, Cyanobacteria and Tenericutes were the most abundant taxonomic groups. The relative abundance of Firmicutes, Proteobacteria and Cyanobacteria in the model group was higher than that in the normal group. On the contrary, the relative abundance of Bacteroidetes in the model group was lower than that in the normal group. Upon XYS treatment, the relative abundance of all dysregulated phyla was restored to levels similar to those observed in the normal group. Abundance clustering heat map of phyla corroborated the taxonomic distribution. CONCLUSION The microbiome relative abundance of FD rats with liver depression-spleen deficiency syndrome was significantly different from the normal cohort. XYS intervention may effectively adjust the gut dysbacteriosis in FD.
文摘Objective:To observe changes in the molecular expression of the NLR Family Pyrin Domain Containing Protein 3(NLRP3)pathway in depressed rats after treatment with Xiaoyaosan,and identify the regulatory mechanism of this compound.Methods:Male SpragueeD awley rats were randomly divided into five groups with 12 rats in each group,including the control group,model group,Fluoxetine group,Xiaoyaosan group,and MCC950 group.A depression model was generated by chronic immobilization stress(induced by 3 h of restraint immobilization every day),and the drugs were administered at the same time in each group for 21 days.The effects of Xiaoyaosan on behavioral changes of depressed rats were observed through macroscopic characterization,body mass,open field experiments,and a sucrose preference test.The m RNA and protein expression of the NLRP3 signaling pathway was examined by fluorescence real-time quantitative PCR and Western blot assays.Results:The Xiaoyaosan group,Fluoxetine group,and MCC950 group rats showed improved depressive behavior and an increased weight of sucrose water consumption.The protein and mRNA expression levels of NLRP3,Caspase-1,and IL-1 b were also decreased in the Fluoxetine,Xiaoyaosan,and MCC950 groups.Conclusion:NLRP3,Caspase-1,and IL-1 b protein and mRNA expression levels were increased in the cortex of depressed rats,while Xiaoyaosan protected cortical tissue in these rats by decreasing NLRP3,Caspase-1,and IL-1 b protein and mRNA expression.
文摘OBJECTIVE Depression is one of the prevalent and prominent complex psychiatric diseases and the number of depressed patients has been on the rise globally during the recent decades.Xiaoyaosan,as a famous Chinese herbal formula,has been widely used in depression patients for a long time. However,the therapeutic mechanisms remain uncertain because of difficulty of depression pathophysiology and the lack of bioinformatic approach to understand the molecular connection. METHODS In this thesis,we applied a network pharmacology approach to explain the potential mechanisms between Xiaoyaosan and depression involved in oral bioavailability screening,drug-likeness assessment,caco-2 permeability,blood-brain barrier target recognition and network analysis. RESULTS 66 active compounds in Xiaoyaosan formula with favorable pharmacokinetic profiles are predicted as active compounds for anti-depression treatment. Network analyses show that these 66 compounds target 40depression-associated proteins including especially HTR2A,NR 3C1,MAOB,XDH and CNR2. These proteins are mainly involved in the neuroactive ligand-receptor interaction,serotonergic synapse,cAMP signaling pathways and calcium signaling pathways. CONCLUSION The integrated network pharmacology method is an effective approach to illustrate the anti-depression mechanisms of herbs,and this in silico approach can be applied in drug discovery.
基金a Grant from the Ministry of Education of the People’s Republic of China,No.NCET-05-0750a Grant from Guangdong Provincial Natural Science Research Team,No.5200491
文摘in hippocampal neurons is an important contributor to depression. [Ca^2＋]i of hippocampal neurons may raise rapidly with increased corticosterone concentrations, leading to apoptosis. The anti-depressant effects of Xiaoyaosan （Free and Easy Wanderer＇s Powder） may inhibit apoptosis by down regulating the [Ca^2＋]i overload. PC12 cells were containing with corticosterone to simulate neuronal injury, dosed with Xiaoyaosan-containing serum, and the following parameters were measured： apoptosis,[Ca^2＋]i overload, and changes in mitochondrial membrane potential （△ψm） and bioenergetics. High-dose Xiaoyaosan-containing serum （the dose of intragastric administration was 2.633 g herb/mL） not only inhibited morphological injury and cell apoptosis, but also suppressed [Ca^2＋]i overload induced by corticosterone. Xiaoyaosan also blocked the decrease in mitochondrial membrane potential and adenosine triphosphate levels induced by corticosterone. Xiaoyaosan dose-dependently suppresses corticosterone-induced apoptosis, potentially via inhibiting [Ca^2＋]ioverload, and prevents impaired mitochondrial bioenergetics by maintaining mitochondrial membrane potential and adenosine triphosphate production, providing a putative mechanism for its antidepressant effects.
文摘The antidepressive effect of Xiaoyaosan is doubtless by researches while the potential antidepressive ac- tive ingredients and their mechanisms remain unclear. In order to explain the antidepressive effect of Xiaoyaosan, all of the recent reports were sought out on the current situation of the antidepressive monomer compositions of Xi- aoyaosan and their mechanism. By exploring the relationship between the effects and the active ingredients, the mechanism and the active ingredients, the antidepressive active ingredients such as quercetin, isorhamnetin, isoliquiritigenin, saikosaponinA, saikosaponinD, glycyrrhiz- kaempferol, liquiritin, isoliquiritin, liquiritigenin, inate, paeoniflorin, albiflorin, ferulic acid, curcumin and their mechanism of antidepressive such as regulating the monoamine neurotransmitter systems, regulating the neuroendocrine system, affecting the neural plasticity and neu- affecting the cytokines level, anti-oxidative stress were rotrophic, affecting the cellular and molecular mechanisms , summarized. By the overview in the level of monomer rather than formulae, we uncovered the antidepressive mech- anism of Xiaoyaosan and further confirmed that Xiaoyaosan, as a classic antidepressive Chinese prescription, had many characteristics, such as multi-level , multi-channel, multi-target and so on .
文摘Aim The study focused on identification and antidepression active verification of constituents from An- gelica Sinensis Radix contrubuting to Xiaoyaosan based on UPLC-PDA guided isolation technique. Methods The UPLC-PDA chromatogram of Xiaoyaosan was compared with that of Angelica Sinensis Radix. The relative retention time of each peak and the Uhraviolet spectra providing by PDA were used in the analyses. Constituents were isola- ted from Angelica Sinensis Radix under the guidance of UPLC-PDA investigation. Structures of the isolates were elu- cidated by NMR techniques. Anti-depression effect was evaluated on glutamate-induced neurons. Results Five marker peaks of Xiaoyaosan fingerprint were belong to Angelica Sinensis Radix, and they were determined as conife- ryl ferulate（ I）, E-butylidenephthalide （ II）, ligustilide （III）, Z-butylidenephthalide （ IV ）, 14-Acetoxy-12-sene- cioyloxytetradeca-2E,8E,10E-trien-4,6-diyn-l-ol（V）. Compound V was isolated from the plants of Umbelliferae for the first time. Treatment with compound I, III, IV can protect PC12 and SH-SY5Y cell from glutamate-induced cytotoxicity. Antidepression bioactivity of compound I was first investigated. Conclusion UPLC-PDA guided iso-lation technique was confirmed to be a rapid and accurate method to identify the main active constituents from An- gelica Sinensis Radix contrubuting to Xiaoyaosan.
基金Supported by the National Natural Science Foundation of China(No.82304746)Jinan University Innovation and Entrepreneurship Training Program for Undergraduate(No.CX21255 and CX22481)。
文摘The hippocampus is one of the most commonly studied brain regions in the context of depression.The volume of the hippocampus is significantly reduced in patients with depression,which severely disrupts hippocampal neuroplasticity.However,antidepressant therapies that target hippocampal neuroplasticity have not been identified as yet.Chinese medicine(CM)can slow the progression of depression,potentially by modulating hippocampal neuroplasticity.Xiaoyaosan(XYS)is a CM formula that has been clinically used for the treatment of depression.It is known to protect Gan(Liver)and Pi(Spleen)function,and may exert its antidepressant effects by regulating hippocampal neuroplasticity.In this review,we have summarized the association between depression and aberrant hippocampal neuroplasticity.Furthermore,we have discussed the researches published in the last 30 years on the effects of XYS on hippocampal neuroplasticity in order to elucidate the possible mechanisms underlying its therapeutic action against depression.The results of this review can aid future research on XYS for the treatment of depression.
基金funded by the National S and T Major Projects for“orjec New Drugs Innovation and Developmente(2017ZX09301047)the Science and Technology of Shanxi Province(No.201701D121137 and No.201903D321210)。
文摘Depression is one of the most prevalent and serious mental disorders with a significant burden of disease.Xiaoyaosan(XYS),a well-known Chinese formula,has been widely used in the treatment of depression.Both clinical studies and animal experiments have indicated that XYS has an obvious antidepressant activity.How to select objective pharmacodynamic markers for traditional Chinese medicine(TCM)treatments based on clinical metabolites,linking pathogenic genes,and drug targets,is a bottleneck problem in the modernization of TCM.To address this issue,we sorted out clinical metabonomics experiments of XYS in treating depression,constructed a metabolic profile of therapeutic biomarkers,and deduced metabolic biomarker-protein interactions networks.The therapeutic biomarkers found for XYS were involved in neurotransmitter synthesis,energy metabolism,and gut microbial metabolism.This study aims to provide a scientific basis for the clinical diagnosis of depression and evaluate the efficacy of XYS in its treatment.
基金supported by The key R and D projects of Shanxi Province(No.201603D3113013)The Science and Technology of Shanxi Province(No.201603D321077 and 201701D121137)+2 种基金The Creative Project for Postgraduate Education in Shanxi province in 2016(No.2016SY007)Shanxi Key Laboratory of Active constituents Research and Utilization of TCM(No.201605D111004)and the Program for the Outstanding Innovative Teams of Higher Learning Institutions of Shanxi(OIT)(No.201605D131045‑18)
文摘Objective: Depression is one of the prevalent and prominent complex psychiatric diseases, and the number of depressed patients has been on the rise globally during the recent decades.Xiaoyaosan, as a famous Chinese herbal formula, has been widely used in depression patients for a long time.However, the therapeutic mechanisms remain uncertain because of the difficulty of depression pathophysiology and the lack of bioinformatic approach to understand the molecular connection.Materials and Methods: In this thesis, we applied a network pharmacology approach to explain the potential mechanisms between Xiaoyaosan and depression involved in oral bioavailability screening, drug-likeness assessment, caco-2 permeability, blood–brain barrier target recognition, and network analysis.Results: Sixty-six active compounds in Xiaoyaosan formula with favorable pharmacokinetic profiles are predicted as active compounds for antidepression treatment.Network analyses showed that these 66 compounds target 40 depression-associated proteins including especially HTR2A, NR3C1, monoamine oxidase inhibitor B, XDH, and CNR2.These proteins are mainly involved in the neuroactive ligand–receptor interaction, serotonergic synapse, cAMP signaling pathways, and calcium signaling pathways.Conclusion: The integrated network pharmacology method can provide a new approach for understanding the pathogenesis of depression and uncovering the molecular mechanisms of Xiaoyansan, which will also facilitate the application of traditional Chinese herbs in modern medicine.
