Effects and mechanisms of traditional Chinese medicines on functional dyspepsia: A review.

Functional dyspepsia (FD) is a common and frequently occurring disease in clinic. With the influence of environmental factors, social factors and dietary factors, the incidence rate of FD in the general population is yearly increasing. Traditional Chinese medicine has a long history and far-reaching influence in the treatment of FD. It can prevent and treat FD in the form of multiple-components, targets and channels, with obvious effect and prominent advantages. This article starts with the common syndrome types of FD, and discusses the research progress of single Chinese medicine, effective ingredients and the mechanism of traditional Chinese medicines in treating FD, in order to provide a theoretical basis for the treatment of FD with traditional Chinese medicines.

Network pharmacology and experimental studies for deciphering the molecular targets and mechanisms of Chaihu Shugan powder in the treatment of functional dyspepsia.

BACKGROUND: Chaihu Shugan powder (CSP) is a prevalent prescription product used in the treatment functional dyspepsia (FD) in China. However, the underlying pharmacological mechanisms involved in the treatment of FD remain unclear. OBJECTIVE: To explore the key components of CSP and their molecular targets and mechanisms in the treatment of FD. METHODS: Active compounds for CSP were identified from the TCMSP and SymMap databases, and the relevant targets were predicted. FD-related targets were obtained from the GeneCards and CTD database. In addition, using the protein-protein interactions (PPI) analysis, the common targets were obtained. Furthermore, the compound-target networks were created with Cytoscape. Finally, molecular docking was performed to identify the core targets and validate them experimentally. RESULTS: In total, 78 active compounds and 671 related targets of CSP were obtained. PPI network analysis identified 15 key FD-related compound targets. Molecular docking revealed that sitosterol and hyndarin exhibited good binding activities with AKT1 and IL6, respectively. Animal experiments have shown that CSP effectively increased the protein levels of AKT1 and reduced the serum levels of IL-6 in FD rats. CONCLUSION: This study provides a theoretical evidence for the analysis of the molecular targets and mechanisms of the action of CSP in FD.

Effects and mechanisms of traditional Chinese medicines on functional dyspepsia: A review / 中草药·英文版

Functional dyspepsia (FD) is a common and frequently occurring disease in clinic. With the influence of environmental factors, social factors and dietary factors, the incidence rate of FD in the general population is yearly increasing. Traditional Chinese medicine has a long history and far-reaching influence in the treatment of FD. It can prevent and treat FD in the form of multiple-components, targets and channels, with obvious effect and prominent advantages. This article starts with the common syndrome types of FD, and discusses the research progress of single Chinese medicine, effective ingredients and the mechanism of traditional Chinese medicines in treating FD, in order to provide a theoretical basis for the treatment of FD with traditional Chinese medicines.

Effects of Chaihu Shugan Powder （柴胡疏肝散） on Duodenal Mucosal Barrier and Intestinal Flora in Functional Dyspepsia Model Rats / 中医杂志

ObjectiveTo study the possible mechanism of Chaihu Shugan Powder （柴胡疏肝散， CSP） in the treatment of functional dyspepsia （FD）. MethodsTwenty-four SD rats were randomly divided into a normal group， a model group， a CSP group and a probiotic group， with six rats in each group.The tail-clamping provocation method was used in all groups except for the normal group to replicate the FD rat model. Simultaneously， the normal group and the model group were given 10 ml/（kg·d） of saline by gavage， while the CSP group and the probiotic group were given 9.6 g/（kg·d） of CSP aqueous decoction and 0.945 g/（kg·d） of probiotic aqueous solution by gavage， respectively， twice daily for four weeks. After four weeks， the gastric emptying and small intestinal propulsion rates were detected in each group of rats. Hematoxylin-eosin （HE） staining was used to observe the histopathological changes in the gastric sinusoids and duodenum of the rats. The changes in the intestinal flora were analyzed by 16s rDNA high-throughput gene sequencing， and the expressions of the duodenal zona occludin 1 （ZO-1） and Occludin were detected by immunohistochemistry and western blotting. Pearson correlation analysis was performed on intestinal flora and ZO-1 and Occludin protein expression. ResultsThe gastric antrum tissue structure was clear in all groups， and the gland structure was regular， with smooth gastric tissue mucosa and no pathological changes such as erosion and ulcer. Compared to those in the normal group， the intestinal villi in the duodenal tissue in the model group were significantly reduced or atrophied， and the goblet cells were arranged in disorder， with eosinophilic infiltration； the gastric emptying rate and small intestinal propulsion rate， as well as ZO-1 and Occludin protein expression in duodenal tissue significantly decreased （P＜0.01）. Compared to those in the model group， the duodenal tissue structure was clear， and the length intestinal villi was longer， with goblet cells neatly arranged in the CSP group and the probiotic group； no obvious eosinophil infiltration was found， and the gastric emptying rate and small intestinal propulsion rate as well as ZO-1 and Occludin protein expression significantly increased in the CSP group； a small amount of eosinophil infiltration was found， and the gastric emptying rate and Occludin protein expression significantly increased in the probiotic group （P＜0.05 or P＜0.01）. Beta diversity analysis of intestinal flora showed that the overall structure of intestinal flora in the model group changed significantly compared to that in the normal group （P＜0.01）. The overall structure of the intestinal flora in the CSP group and the probiotic group was closer to the normal group than the model group. Species composition analysis showed that the relative abundance of the Firmicutes decreased， while the relative abundance of the Bacteroidetes and norank_f_Muribaculaceae increased， and the Bacteroidetes/Firmicutes value increased in the model group than those in the normal group （P＜0.05 or P＜0.01）. Compared to those in the model group， the relative abundance of the Firmicutes increased， while the relative abundance of the Bacteroidetes and norank_f_Muribaculaceae， as well as the Bacteroidetes/Firmicutes value decreased in the CSP group and the probiotic group （P＜0.05 or P＜0.01）. There was no statistically significant difference in each indicator between the probiotic group and the CSP group （P＞0.05）. Pearson correlation analysis showed that at the phylum level， Firmicutes was positively correlated with ZO-1 （r=0.610， P=0.016） and Occludin （r=0.694， P=0.004） protein expression. Bacteroidetes was negatively correlated with ZO-1 （r=-0.557， P=0.031） and Occludin （r=-0.662， P=0.007） protein expression. At the genus level， norank_f_Muribaculaceae was negatively correlated with ZO-1 （r=-0.727， P=0.002） and Occludin （r=-0.760，P=0.001） protein expression. ConclusionCSP can restore the structure of intestinal flora， regulate the abundance levels of Firmicutes， Bacteroidetes and norank_f_Muribaculaceae， up-regulate ZO-1 and Occludin proteins， and thus repairing the duodenal mucosal barrier， and playing a therapeutic role in FD rats.

[Study on protective effect of Chaihu Shugan Powder against liver injury in rats with intrahepatic cholestasis by regulating FXR/Nrf2/ARE pathway].

This study aims to investigate the effect of Chaihu Shugan Powder(CHSG) on liver injury in rats with intrahepatic cholestasis by regulating farnesoid X receptor(FXR)/nuclear factor erythroid-2-related factor(Nrf2)/antioxidant response element(ARE) pathway. Eighty-four SD rats were classified into normal group, model group, CHSG-L group(0.5 g·kg~(-1)), CHSG-H group(2.5 g·kg~(-1)), ursodeoxycholic acid group(UDCA group, 100 mg·kg~(-1)), CHSG-H+sh-NC group(2.5 g·kg~(-1) CHSG+subcutaneous injection of sh-NC lentivirus), CHSG-H+sh-FXR group(2.5 g·kg~(-1) CHSG+subcutaneous injection of sh-FXR lentivirus), with 12 rats in each group. Rats were treated with corresponding drugs except for the normal group and the model group, once a day, for 7 days. On 5 th day, rats, except the normal group, were given α-naphthalene isothiocyanate(ANIT) at a dose of 100 mg·kg~(-1), once a day for 3 days to induce intrahepatic cholestasis, and the normal group was given the same amount of normal saline. Rats were anesthetized 1 h after the last administration and the 2 h bile flow was measured. Aeroset chemistry analyzer was employed to detect the levels of alanine aminotransferase(ALT), aspartate aminotransferase(AST), total bilirubin(TBIL), and total bile acid(TBA) in rat serum. Based on hematoxylin and eosin(HE) staining, the pathological changes of rat liver tissue were observed. Glutathione peroxidase(GSH-Px), superoxide dismutase(SOD), and malondialdehyde(MDA) in rat liver tissue homogenate were monitored with corresponding kits. Western blot was used to detect the expression of FXR, Nrf2, and heme oxygenase-1(HO-1) proteins in rat liver tissue. Compared with the normal group, the model group showed many spots or concentrated necrotic areas in the liver tissue, infiltration of a large number of inflammatory cells, swelling liver cells with nuclear shrinkage. The 2 h bile flow, levels of GSH-Px and SOD, and relative expression of FXR, Nrf2, and HO-1 proteins were significantly lower, and the levels of ALT, AST, TBIL, TBA and MDA were significantly higher in the model group than in the normal group. Compared with the model group, CHSG-L group, CHSG-H group, and UDCA group demonstrated significant alleviation of pathological damage of the liver tissue, significantly high 2 h bile flow, levels of GSH-Px and SOD, and expression of FXR, Nrf2 and HO-1 proteins, and significantly low levels of ALT, AST, TBIL, TBA and MDA. Compared with the CHSG-H group, the CHSG-H+sh-FXR group had worse liver pathological damage, significantly low levels of 2 h bile flow, levels of GSH-Px and SOD, and expression of FXR, Nrf2, and HO-1 proteins, and significantly high levels of ALT, AST, TBIL, TBA, and MDA. CHSG may protect against liver injury in rats with intrahepatic cholestasis by activating the FXR/Nrf2/ARE pathway.

Chaihu Shugan powder alleviates liver inflammation and hepatic steatosis in NAFLD mice: A network pharmacology study and in vivo experimental validation.

Background: Nonalcoholic fatty liver disease (NAFLD) is the most common metabolic disease and is intertwined with cardiovascular disorders and diabetes. Chaihu Shugan powder (CSP) is a traditional Chinese medicine with a significant therapeutic effect on metabolic diseases, such as NAFLD. However, its pharmacological mechanisms remain to be elucidated. Methods: The main compounds of CSP were measured using LC-MS/MS. A network pharmacology study was conducted on CSP. Its potential active ingredients were selected according to oral bioavailability, drug similarity indices, and phytochemical analysis. After obtaining the intersected genes between drug targets and disease-related targets, the component-disease-target network and protein-protein interaction analysis were visualized in Cytoscape. GO and KEGG enrichment analyses were performed using the Metascape database. Six-week-old male C57BL/6 mice fed a high-fat high-fructose diet for 16 weeks plus chronic immobilization stress for 2 weeks, an in vivo model, were administered CSP or saline intragastrically. Liver histology, triglyceride and cholesterol levels, ELISA, and RT-PCR were used to assess hepatic inflammation and steatosis. Immunohistochemistry and western blotting were performed to assess protein levels. Results: A total of 130 potential target genes in CSP that act on NAFLD were identified through network pharmacology assays, including tumor necrosis factor (TNF), interleukin-6 (IL6), interleukin-1ß (IL-1ß), and peroxisome proliferator-activated receptor γ (PPARG). KEGG enrichment analysis showed that the main pathways were involved in inflammatory pathways, such as the TNF and NF-κB signaling pathways, and metabolism-related pathways, such as the MAPK, HIF-1, FoxO, and AMPK signaling pathways. The results in vivo showed that CSP ameliorated liver inflammation and inhibited hepatic fatty acid synthesis in the hepatocyte steatosis model. More specifically, CSP therapy significantly inhibited the expression of tumor necrosis factor α (TNFα), accompanied by a decrease in TNF receptor 1 (TNFR1) and the ligand availability of TNFR1. Conclusion: Through the combination of network pharmacology and in vivo validation, this study elucidated the therapeutic effect of CSP on NAFLD, decreasing liver inflammation and inhibiting hepatic fatty acid synthesis. More specifically, the anti-inflammatory action of CSP was at least partially mediated by inhibiting the TNFα/TNFR1 signaling pathway.

A Chinese Classical Prescription Chaihu Shugan Powder in Treatment of Post-Stroke Depression: An Overview.

Post-stroke depression (PSD) is the most common mental health problem after a stroke with an incidence of up to 33%. PSD has a negative impact on the rehabilitation and recovery of motor and cognitive dysfunction after a stroke and significantly increases the chance of the recurrence of neurovascular events. At present, medication is the preferred method of coping with PSD. Modern medicine is still unclear regarding the pathogenesis of PSD, with clinical drug treatment mostly using antidepressants, such as selective serotonin reuptake inhibitor (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs). However, a high proportion of patients fail to show an adequate antidepressant response and have adverse reactions after taking antidepressants. In recent years, as the advantages of traditional Chinese medicine (TCM) in clinical treatment continue to emerge, Chinese herbal and TCM formulae have begun to enter the awareness of Chinese scholars and even scholars around the world. As a classic formula with a history of more than 400 years, Chaihu Shugan powder (CHSG) has great advantages in the clinical treatment of PSD. Based on existing clinical and experimental studies, this article comprehensively analyzes clinical cases, mechanisms of action, and drug and chemical effects of CHSG in the treatment of PSD in order to provide more clinical experience and experimental theoretical support for CHSG in the treatment of PSD.

[Antidepressant mechanism of Shugan Lipi recipe in regulating tryptophan metabolism and its common pharmacodynamic substances].

This article is to explore the antidepressant mechanism of Shugan Lipi recipe in regulating tryptophan metabolism,and to find out their common pharmacodynamic substances. UPLC-Q-TOF-MS technology was used to establish fingerprints of Shugan Lipi recipe,and 124 components were identified. The depressed mouse model was replicated by triple-one multiple stress method. Chaihu Shugan Powder,Sini Powder and Xiaoyao Powder were administered in groups to observe the changes in body weight and behavior of the mice. The results showed that compared with the model group,the body weight,sucrose preference percentage and autonomous activity behavior of each administration group were improved. Among them,the effect of Chaihu Shugan Powder was better than that of Sini Powder and Xiaoyao Powder. LC-MS/MS method was used to determine the contents of 5-hydroxytryptamine( 5-HT),kynurenine( KYN) and tryptophan( TPP) in blood,liver,brain,colon and other tissues,as well as TDO enzyme activity in liver. Western blot and RT-PCR were used to detect the protein and gene expression of TDO enzyme,respectively. It was found that the three prescriptions increased the ratio of 5-HT/KYN in different degrees,decreased the ratio of KYN/TRP in liver,colon and brain,and decreased the expression level and activity of TDO enzyme in liver. The order of their ability to regulate tryptophan metabolism was Chaihu Shugan Powder>Sini Powder>Xiaoyao Powder. In addition,the correlation between the chromatographic peaks in the fingerprints of Shugan Lipi recipes and the pharmacodynamic indexes of tryptophan metabolism was analyzed by the grey relation analysis. The grey relation analysis found that the chemical components with the highest correlation with tryptophan metabolism were mainly from Paeoniae Radix Alba,Citri Reticulatae Pericarpium,Aurantii Fructus Immaturus and Aurantii Fructus. UPLC-Q-TOF-MS was used to analyze the migration components in the plasma of mice after administration of Shugan Lipi recipe,and to verify the common pharmacodynamic substances of Shugan Lipi recipe. The migration of these detected components in plasma was studied,and a total of 18 prototype components and 36 metabolites were identified. Therefore,it was believed that Chaihu Shugan Powder,Sini Powder and Xiaoyao Powder could play an antidepressant role by reducing the expression of TDO enzyme in the liver and regulating the metabolism of tryptophan.The components contained in Paeoniae Radix Alba,Citri Reticulatae Pericarpium,Aurantii Fructus Immaturus and Aurantii Fructus were the common pharmacodynamic substances of Shugan Lipi recipe,which played an important role in regulating tryptophan metabolism.

Antidepressant-Like Effects of Chaihu Shugan Powder () on Rats Exposed to Chronic Unpredictable Mild Stress through Inhibition of Endoplasmic Reticulum Stress-Induced Apoptosis.

OBJECTIVE: To investigate the antidepressant-like effects of Chaihu Shugan Powder (CSP, ) and to explore its underlying mechanisms. METHODS: Thirty-two Sprague-Dawley rats were randomly divided into control (CON), chronic unpredictable mild stress (CUMS), fluoxetine (FLU), and CSP groups, 8 rats in each group. All of the rats except for those in the control group were subjected to 3 consecutive weeks of CUMS to establish the depression model. The open field test (OFT), forced swimming test (FST), and sucrose preference test were used to assess the anti-anxiety and antidepressant effects of CSP. Terminal deoxynucleotidyl transferase (TdT) dUTP nick-end labeling was used to determine the apoptosis rate in the hippocampal tissues. The mRNA and protein levels of glucose-regulated protein (GRP) 78, spliced X-box-binding protein (XBP)-1, CCAAT/enhancer-binding protein homologous protein (CHOP), caspase-12, and c-Jun N-terminal kinase (JNK) in the hippocampus of rats were evaluated by real-time PCR and Western blot analysis, respectively. RESULTS: Administration of CSP alleviated anxiety and depression-like behavior in CUMS rats, as revealed by enhanced time and distance in the center of the OFT (P<0.05), an increased preference for sucrose, and longer swimming time and shorter immobility time during the FST (all P<0.05). In addition, CSP treatment significantly reduced the rate of apoptosis in rat hippocampal neurons (P<0.05). The mRNA and protein expression levels of GRP78, spliced XBP-1, and CHOP were down-regulated along with the expression of caspase-12 and cleaved caspase-12 proteins (all P<0.05), whereas total and phosphorylated JNK1 protein levels did not differ significantly between control and CSP-treated rats. CONCLUSION: CSP can improve depression-like behavior in rats exposed to CUMS, possibly by suppressing CHOP and caspase-12 mediated apoptosis in the rat hippocampus.

Antidepressant-Like Effects of Chaihu Shugan Powder () on Rats Exposed to Chronic Unpredictable Mild Stress through Inhibition of Endoplasmic Reticulum Stress-Induced Apoptosis / 中国结合医学杂志

OBJECTIVE@#To investigate the antidepressant-like effects of Chaihu Shugan Powder (CSP, ) and to explore its underlying mechanisms.@*METHODS@#Thirty-two Sprague-Dawley rats were randomly divided into control (CON), chronic unpredictable mild stress (CUMS), fluoxetine (FLU), and CSP groups, 8 rats in each group. All of the rats except for those in the control group were subjected to 3 consecutive weeks of CUMS to establish the depression model. The open field test (OFT), forced swimming test (FST), and sucrose preference test were used to assess the anti-anxiety and antidepressant effects of CSP. Terminal deoxynucleotidyl transferase (TdT) dUTP nick-end labeling was used to determine the apoptosis rate in the hippocampal tissues. The mRNA and protein levels of glucose-regulated protein (GRP) 78, spliced X-box-binding protein (XBP)-1, CCAAT/enhancer-binding protein homologous protein (CHOP), caspase-12, and c-Jun N-terminal kinase (JNK) in the hippocampus of rats were evaluated by real-time PCR and Western blot analysis, respectively.@*RESULTS@#Administration of CSP alleviated anxiety and depression-like behavior in CUMS rats, as revealed by enhanced time and distance in the center of the OFT (P<0.05), an increased preference for sucrose, and longer swimming time and shorter immobility time during the FST (all P<0.05). In addition, CSP treatment significantly reduced the rate of apoptosis in rat hippocampal neurons (P<0.05). The mRNA and protein expression levels of GRP78, spliced XBP-1, and CHOP were down-regulated along with the expression of caspase-12 and cleaved caspase-12 proteins (all P<0.05), whereas total and phosphorylated JNK1 protein levels did not differ significantly between control and CSP-treated rats.@*CONCLUSION@#CSP can improve depression-like behavior in rats exposed to CUMS, possibly by suppressing CHOP and caspase-12 mediated apoptosis in the rat hippocampus.

Antidepressant mechanism of Shugan Lipi recipe in regulating tryptophan metabolism and its common pharmacodynamic substances / 中国中药杂志

This article is to explore the antidepressant mechanism of Shugan Lipi recipe in regulating tryptophan metabolism,and to find out their common pharmacodynamic substances. UPLC-Q-TOF-MS technology was used to establish fingerprints of Shugan Lipi recipe,and 124 components were identified. The depressed mouse model was replicated by triple-one multiple stress method. Chaihu Shugan Powder,Sini Powder and Xiaoyao Powder were administered in groups to observe the changes in body weight and behavior of the mice. The results showed that compared with the model group,the body weight,sucrose preference percentage and autonomous activity behavior of each administration group were improved. Among them,the effect of Chaihu Shugan Powder was better than that of Sini Powder and Xiaoyao Powder. LC-MS/MS method was used to determine the contents of 5-hydroxytryptamine( 5-HT),kynurenine( KYN) and tryptophan( TPP) in blood,liver,brain,colon and other tissues,as well as TDO enzyme activity in liver. Western blot and RT-PCR were used to detect the protein and gene expression of TDO enzyme,respectively. It was found that the three prescriptions increased the ratio of 5-HT/KYN in different degrees,decreased the ratio of KYN/TRP in liver,colon and brain,and decreased the expression level and activity of TDO enzyme in liver. The order of their ability to regulate tryptophan metabolism was Chaihu Shugan Powder>Sini Powder>Xiaoyao Powder. In addition,the correlation between the chromatographic peaks in the fingerprints of Shugan Lipi recipes and the pharmacodynamic indexes of tryptophan metabolism was analyzed by the grey relation analysis. The grey relation analysis found that the chemical components with the highest correlation with tryptophan metabolism were mainly from Paeoniae Radix Alba,Citri Reticulatae Pericarpium,Aurantii Fructus Immaturus and Aurantii Fructus. UPLC-Q-TOF-MS was used to analyze the migration components in the plasma of mice after administration of Shugan Lipi recipe,and to verify the common pharmacodynamic substances of Shugan Lipi recipe. The migration of these detected components in plasma was studied,and a total of 18 prototype components and 36 metabolites were identified. Therefore,it was believed that Chaihu Shugan Powder,Sini Powder and Xiaoyao Powder could play an antidepressant role by reducing the expression of TDO enzyme in the liver and regulating the metabolism of tryptophan.The components contained in Paeoniae Radix Alba,Citri Reticulatae Pericarpium,Aurantii Fructus Immaturus and Aurantii Fructus were the common pharmacodynamic substances of Shugan Lipi recipe,which played an important role in regulating tryptophan metabolism.

A network pharmacology-based approach to explore the effects of Chaihu Shugan powder on a non-alcoholic fatty liver rat model through nuclear receptors.

The pathogenesis of non-alcoholic fatty liver disease (NAFLD) is still not fully understood, and currently, no effective pharmacotherapy is available. Nuclear receptors (NRs) are important biological participants in NAFLD that exhibit great therapeutic potential. Chaihu Shugan powder (CSP) is a traditional Chinese medicine (TCM) formula that has a wide therapeutic spectrum including NAFLD, but the effective components and functional mechanisms of CSP are unclear. We adopted a network pharmacology approach using multiple databases for Gene Ontology (GO) enrichment analysis and the molecular complex detection (MCODE) method for a protein-protein interaction (PPI) analysis, and we used molecular docking method to screen the NR targets and determine the corresponding CSP components. The screening results were validated through a NAFLD rat model that was used to explain the possible relationship between CSP and NAFLD. Finally, we screened PPARγ, FXR, PPARα, RARα and PPARδ as target genes and quercetin, kaempferol, naringenin, isorhamnetin and nobiletin as target compounds. The five components were detected through high-performance liquid chromatography-mass spectrometry (HPLC-MS), the results of which aligned with the docking experiments of PPARγ, PPARα and PPARδ. After CSP intervention, the NAFLD rat model showed ameliorated effects in terms of bodyweight, hepatic histopathology, and serum and liver lipids, and the mRNA levels of PPARγ, FXR, PPARα and RARα were significantly changed. The results from this study indicate that CSP exhibits healing effects in an NAFLD model and that the network pharmacology approach to screening NR targets and determining the corresponding CSP components is a practical strategy for explaining the mechanism by which CSP ameliorates NAFLD.

Mechanism of Chaihu Shugan Powder () for Treating Depression Based on Network Pharmacology.

OBJECTIVE: To analyze the effective components of Chinese medicine (CM) contained in Chaihu Shugan Powder (, CSP) in the treatment of depressive disorders and to predict its anti-depressant mechanism by network pharmacology. METHODS: Absorption, distribution, metabolism, excretion, and toxicity calculation method was used to screen the active components of CSP. Traditional Chinese Medicine System Pharmacological Database Analysis Platform and text mining tool (GoPuMed database) were used to predict and screen the active ingredients of CSP and anti-depressive targets. Through Genetic Association Database, Therapeutic Target Database, and PharmGkb database targets for depression were obtained. Cytoscape3.2.1 software was used to establish a network map of the active ingredients-targets of CSP, and to analyze gene function and metabolic pathways through Database for Annotation, Visualization and Integrated Discovery and the Omicshare database. RESULTS: The 121 active ingredients and 15 depression-related targets which were screened from the database can exert antidepressant effects by improving the neural plasticity, growth, transfer condition and gene expression of neuronal cell, and the raise of the expression of gap junction protein. The 15 targets passed 14 metabolic pathways, mainly involved in the regulation of neurotransmitters (5-hydroxytryptamine, dopamine and epinephrine), inflammatory mediator regulation of TRP channels, calcium signaling pathway, cyclic adenosine monophosphate signaling pathway and neuroactive ligand-receptor interaction and other signal channels to exert anti-depressant effects. CONCLUSION: This article reveals the possible mechanism of CSP in the treatment of depression through network pharmacology research, and lays a foundation for further target studies.

Mechanism of Chaihu Shugan Powder () for Treating Depression Based on Network Pharmacology / 中国结合医学杂志

OBJECTIVE@#To analyze the effective components of Chinese medicine (CM) contained in Chaihu Shugan Powder (, CSP) in the treatment of depressive disorders and to predict its anti-depressant mechanism by network pharmacology.@*METHODS@#Absorption, distribution, metabolism, excretion, and toxicity calculation method was used to screen the active components of CSP. Traditional Chinese Medicine System Pharmacological Database Analysis Platform and text mining tool (GoPuMed database) were used to predict and screen the active ingredients of CSP and anti-depressive targets. Through Genetic Association Database, Therapeutic Target Database, and PharmGkb database targets for depression were obtained. Cytoscape3.2.1 software was used to establish a network map of the active ingredients-targets of CSP, and to analyze gene function and metabolic pathways through Database for Annotation, Visualization and Integrated Discovery and the Omicshare database.@*RESULTS@#The 121 active ingredients and 15 depression-related targets which were screened from the database can exert antidepressant effects by improving the neural plasticity, growth, transfer condition and gene expression of neuronal cell, and the raise of the expression of gap junction protein. The 15 targets passed 14 metabolic pathways, mainly involved in the regulation of neurotransmitters (5-hydroxytryptamine, dopamine and epinephrine), inflammatory mediator regulation of TRP channels, calcium signaling pathway, cyclic adenosine monophosphate signaling pathway and neuroactive ligand-receptor interaction and other signal channels to exert anti-depressant effects.@*CONCLUSION@#This article reveals the possible mechanism of CSP in the treatment of depression through network pharmacology research, and lays a foundation for further target studies.

Review of the application and mechanism of Chaihu-Shugan powder for digestive system / 国际中医中药杂志

This review summarizes the clinical and functional mechanisms of Chaihu-Shugan powder in the treatment of digestive system diseases. This prescription shows good curative effect on peptic ulcer, functional dyspepsia, chronic gastritis, nonalcoholic fatty liver, chronic hepatitis B, chronic pancreatitis and ulcerative colitis. The main mechanism is to reduce the immune inflammatory response, improve lipid metabolism, regulate the level of gastrointestinal hormones, and affect Cajal interstitial cells (ICC).

Regulation of Chaihu Shugan Powder on kynurenine in raphe nucleus of depressive rats induced by reserpine / 中华行为医学与脑科学杂志

Objective To investigate the antidepressant effects of Chaihu Shugan Powder(CSP) on depressive rats induced by reserpine and its influences on the kynurenine (KYN),indoleamine 2,3-dioxyge-nase(IDO),interleukin-6(IL-6) and tumor necrosis factor-α( TNF-α). Methods Forty rats with similar behavior results were divide into 4 groups randomly,including Control group(Con),Model group(Res),Flu- oxetine group(Res+Flu) and Chaihu Shugan Powder group(CSP). The depressive rat model was established by intraperitoneal injection reserpine. The rats in Res+Flu group were administered with fluoxetine by intrap-eritoneal and rats in Res+CSP group were administered with CSP by intraperitoneal. After 14 days,the be-havior of rats was measured and then the rats were executed and sampled. The content of tryptophan and kynurenine in raphe nuclei tissue were detected. The mRNA expression level of IDO,IL-6,TNF-α in raphe nuclei tissue were detected. Results ( 1) Compared with Con group (( 81. 81 ± 36. 13) s, ( 83. 51 ± 5. 34)%), the swimming immobility time((150. 50±31. 45)s) in Res group increased(t=68. 7, P<0. 05) and the sucrose perference (59. 73±11. 30)%) in Res group decreased(t=23. 8,P<0. 05). Compared with Res group, the swimming immobility time in Res+Flu group((114. 90± 14. 29) s) and Res+CSP group ((111. 7±11. 34)s) decreased(t=35. 6,35. 8,both P<0. 05). Compared with Res group, the sucrose pref-erence in Res+Flu group((78. 21±10. 07)%) increased(t=18. 3, P<0. 05). (2)Compared with Con group (KYN/TRP:(0. 023±0. 016),IDO mRNA:(1. 00±0. 05),IL-6 mRNA:(1. 00±0. 58),TNF-α mRNA:(1. 00±0. 32)), the activity of IDO(KYN/TRP(0. 039±0. 003)) and the mRNA levels of IDO mRNA(3. 63± 0. 31),IL-6 mRNA(2. 36±0. 23),TNF-α mRNA( 3. 56± 0. 14) of Raphe Nuclei tissue in Res group were significantly increased (t=21. 2,12. 9,38. 3,19. 7,all P<0. 05). Compared with Res group, the activity of IDO(KYN/TRP(0. 030±0. 013)),the mRNA expression levels of IDO mRNA( 1. 56±0. 36),IL-6 mRNA (1. 62±0. 16),TNF-α mRNA(2. 64±0. 20)of Raphe Nuclei tissue in Res+Flu group were significantly de-creased(t=38. 8,15. 8,12. 8,26. 4,all P<0. 05). And compared with Res group,the activity of IDO( KYN/TRP(0. 028±0. 021)) ,the mRNA expression level of IDO mRNA( 1. 33± 0. 29),IL-6 mRNA(1. 36± 0. 34),TNF-α mRNA(1. 93±0. 21)of raphe nuclei tissue in Res+CSP group were also significantly decreased (t=23. 21,17. 3,19. 8,29. 8,all P<0. 05). Compared with Res+Flu group,the level of IDO mRNA and in-flammatory factors' mRNA in Res+CSP group were significantly decreased(t=18. 3,20. 8,31. 5,all P<0. 05). Conclusion Chaihu Shugan Powder has antidepressant effect,and the mechanism is related with de-creasing the inflammatory factors,inhibiting IDO activation and decreasing the IDO mRNA.

Network pharmacology of Chaihu Shugan Powder for treating post-stroke depression / 中草药

Objective: To assess the effective components of Chaihu Shugan Powder in the treatment of post-stroke depression and its potential mechanisms. Methods: The chemical constituents and targets of Chaihu Shugan Powder were obtained from Traditional Chinese Medicine Systems Pharmacology (TCMSP) database. Common targets for stroke and depression were obtained from OMIM, TTD, and PharmGkb databases. Excel was used to filter molecules and targets, so as the Cytoscape software to establish the network between Chinese medicine molecules and target. The biological information annotation database was used to analyze gene function and metabolic pathway. Results: There were 122 Chinese medicine ingredients from databases mteracting with 42 target proteins of post-stroke depression. Finally, five targets including Estrogen receptor (ESR1), prostaglandin G/H synthase 2 (PTGS2), glycogen synthase kinase-3 beta (GSK3β), sodium-dependent dopamine transporter (SLC6A4), and leukotriene A-4 hydrolase (LTA4H) were selected as the action targets for treating post-stroke depression, involved the arachidonic acid metabolism, 5-serotonin ergic synaptic pathway, prolactin signaling pathway, and thyroid hormone signaling pathways, which can treat post-stroke depression by regulating inflammatory response, synapse synthesis, estrogen response, recollection, biosynthesis, drug reaction, and circadian rhythm.Conclusion: The network pharmacology study revealed the underlying mechanisms of Chaihu Shugan Powder for treating the post-stroke depression.

Research Progress in Pharmacological Effects and Mechanism of Chaihu Shugan Powder / 中国中医药信息杂志

Chaihu Shugan Powder has the function of soothing liver and promoting qi flow, activating blood and relieving pain. In clinic, it is mainly used for the syndrome of liver qi stagnation, with wide application. This article reviewed the literature about effects of Chaihu Shugan Powder on neurobiochemistry, endocrine regulation, immunity and antioxidant pharmacological effects and mechanism, with a purpose to provide references for clinical medication and new medicine research.

Effects of Chaihu Shugan powder on hepatic lipid metabolism and AMPK/SIRT1 pathway in rats with non-alcoholic fatty liver disease / 中国病理生理杂志

[ ABSTRACT] AIM:To investigate the effects of Chaihu Shugan powder ( CSP) on lipid metabolism and the pro-teins involved in adenosine 5’-monophosphate-activated protein kinase (AMPK)/sirtuin 1 (SIRT1) pathway in the liver tissues of the rats with non-alcoholic fatty liver disease (NAFLD).METHODS: Sprague-Dawley rats were randomly di-vided into normal control ( NC) group, with HFD ( HFD) group and CSP group.The NAFLD models were established by feeding with HFD for 16 weeks in the rats.The rats in CSP group were intragastrically administered with CSP extracts (9.6 g· kg-1 · d-1 ) , and blood and liver samples were collected 16 weeks later.Serum and liver levels of total cholesterol ( TC) and triglyceride ( TG) , and serum levels of alanine aminotransferase ( ALT) and aspartate aminotransferase ( AST) were measured using an automatic biochemical analyzer.The histological changes of liver tissues were observed with HE staining, while the lipid deposition was observed with Oil Red O staining.The ultrastructural changes of the liver tissues were observed under transmission electron microscope.Moreover, the protein levels of AMPK, phosphorylated AMPK (pAMPK), SIRT1 and uncoupling protein 2 (UCP2) in the liver were detected by Western blot.RESULTS:The results of HE staining, Oil Red O staining and electron microscopy demonstrated that NAFLD rat model was successfully estab-lished.Compared with NC group, the serum and liver levels of TC and TG, and serum level of AST in model group were markedly elevated ( P<0.01) .Moreover, the protein levels of pAMPK and SIRT1 in HFD group were markedly reduced (P<0.01), whereas UCP2 level was elevated (P<0.01).Furthermore, liver levels of TC and TG, and serum level of AST in GSP group were markedly reduced as compared with HFD group ( P<0.05 ) .The protein levels of pAMPK and SIRT1 were elevated ( P<0.05 ) , whereas the UCP2 level was reduced as compared with HFD group ( P<0.01 ) .The protein level of AMPK between the 3 groups had no significant difference.CONCLUSION: CSP attenuates hepatic lipid disorder and hepatic lipid deposition in NAFLD rats induced by feeding with HFD for 16 weeks, which is associated with the activation of AMPK/SIRT1 pathway.

Clinical Observation of Chaihu Shugan Powder Combined with Clonazepam in the Treatment of Liver Qi Stagnation Type Anxiety / 中国药房

OBJECTIVE:To observe clinical efficacy and safety of Chaihu shugan powder combined with clonazepam in the treatment of liver qi stagnation type anxiety. METHODS:96 patients with liver qi stagnation type anxiety were randomly divided in-to observation group and control group,with 48 cases in each group. Control group was given Clonazepam tablet with initial dose of 0.5 mg,increasing to 4.0 mg gradually,tid;observation group was additionally given Chaihu shugan powder 300 ml,bid,on the basis of control group. Both groups were treated for 6 weeks. Clinical efficacy of 2 groups were observed,and HAMA and SAS were observed before and after treatment;the incidence of ADR were compared between 2 groups. RESULTS:The total effective rate of observation group(97.92%)was significantly higher than that of control group(83.33%),with statistical significance(P0.05);HAMA and SAS of 2 groups decreased significantly 1,3 and 6 weeks after treatment,and the observation group was lower than the control group, with statistical significance(P0.05). CONCLUSIONS:Chaihu shugan powder combined with clonazepam is effective,improve patient anxiety and safe in the treatment of liver qi stagnation type anxiety.