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.

BACKGROUND: Chaihu Shugan powder (CSP) plays an important role in the prevention and treatment of nonalcoholic fatty liver disease (NAFLD) through a variety of biological mechanisms. However, whether the mechanism involves microRNA (miRNA) regulation remains unknown.
OBJECTIVE: To investigate the effects of CSP on the miRNA expression profile of rats with NAFLD induced by high-fat diet (HFD), and to explore the mechanism of CSP in the treatment of NAFLD.
METHODS: NAFLD rat models were established by an 8-week HFD. The therapeutic effects of CSP on NAFLD were evaluated by physiological, biochemical and pathological analysis and hepatic surface microcirculation perfusion test. MicroRNA sequencing was used to study the effect of CSP on the miRNA expression profile of NAFLD rats, and the target genes of differentially expressed (DE) miRNAs were predicted for further function enrichment analysis. Next, targets of CSP and NAFLD were collected by a network pharmacological approach, and Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) analysis were performed for the common target genes of CSP, NAFLD and DE miRNAs, and the expression levels of key genes and proteins were verified by quantitative Real-time PCR and Western blot. Finally, a network among formula-herb-compound-miRNA-target-biological processes-disease was established to explained the complex regulation mechanism of CSP on NAFLD.
RESULTS: The results showed that CSP significantly improved liver lipid accumulation, serum lipid and transaminase levels and liver surface microcirculation disturbance in HFD-induced NAFLD rats. The intervention of CSP reversed the high expression of 15 miRNAs in liver tissues induced by HFD, including miR-34a-5p, miR-146a-5p, miR-20b-5p and miR-142-3p. The results of pathway and functional enrichment analysis showed that, CSP might play an anti-NAFLD role via regulating DE miRNAs related to fatty acid metabolic process. Combined with the network pharmacological analysis, it was found that the DE miRNAs might affected the fatty acid biosynthesis pathway in the treatment of NAFLD by CSP. Molecular biology experiments have conformed the decreased the gene and protein levels of acetyl-CoA carboxylase alpha (ACACA), fatty acid synthase (FASN) and other fatty acid biosynthesis related enzymes on NAFLD rats after intervention of CSP.
CONCLUSIONS: CSP can significantly reduce hepatic lipid accumulation of NAFLD rat model induced by HFD, and its mechanism may be through the action of 15 miRNAs such as miR-34a-5p, miR-146a-5p, miR-20b-5p and miR-142-3p. Reduce the gene and protein expression levels of ACACA, FASN and other fatty acid biosynthesis related enzymes, thus reducing fatty acid biosynthesis. Based on an epigenetic perspective, this study explains the key anti-NAFLD mechanism of CSP via combination of microRNA sequencing and network pharmacological analysis, providing a new reference for the modernization of traditional Chinese medicine.

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.
CONCLUSIONS: This study provides a theoretical evidence for the analysis of the molecular targets and mechanisms of the action of CSP in FD.

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.

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.

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-1β (IL-1β), 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.

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.

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.
CONCLUSIONS: CSP can improve depression-like behavior in rats exposed to CUMS, possibly by suppressing CHOP and caspase-12 mediated apoptosis in the rat hippocampus.

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.

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.
CONCLUSIONS: 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.