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1.
Acta Pharmaceutica Sinica ; (12): 1387-1395, 2022.
Article in Chinese | WPRIM | ID: wpr-924766

ABSTRACT

"Omics" and bioinformatics have brought new ideas to the study of traditional Chinese medicine. This study used metabonomics and network pharmacology to investigate the pharmacodynamic basis and regulation of Qishen Yiqi dropping pill (QDP) improving cardiac energy metabolism in rats with heart failure (HF). 1H NMR metabonomics analysis showed that eight metabolites, including carnitine, glutamine, creatine, proline, homocitrulline, lactic acid, taurine and alanine appeared significant callback after QDP treatment for HF. The results indicate that QDP regulates the metabolism of carbohydrate, lipid, ATP and protein. The animal experiment was conducted in accordance with the regulations of the Ethics Committee for Experimental Animal Management and Animal Welfare of Institute of Materia Medica, Chinese Academy of Medical Sciences. A "drug-component-target-disease" network was established using network pharmacology, and the "component-target" sub-network related to the above energy metabolism processes was extracted by combining metabonomics results. Results revealed 79 chemical compounds and 47 potential targets of QDP involved in the regulation of energy metabolism, and identified key chemical components including ursolic acid, notoginsenoside G, ginsenoside-Rh1, and core targets such as INS, PPARG, and AKT1. The results also demonstrated the complex multi-target and multi-component relationship between QDP and HF from the perspective of energy metabolism. The molecular docking technique verified a strong interaction between some targets and chemical compounds, with affinities less than -5 kcal·mol-1. The results of this study provide useful information for the clinical application, development, and utilization of QDP.

2.
Acta Pharmaceutica Sinica ; (12): 1477-1485, 2022.
Article in Chinese | WPRIM | ID: wpr-924760

ABSTRACT

Da Chaihu decoction is a classic prescription for the treatment of cholecystitis that is widely used in clinical practice, and has a definite curative effect. However, due to its diverse components and complex functions, the traditional indexes fail to capture its overall efficacy. Therefore, this study analyzed and predicted the quality markers (Q-markers) of Da Chaihu decoction based on specific chromatogram and network pharmacology to provide a reference for the comprehensive control of the quality. The study obtained 35 potential practical components of Da Chaihu decoction through virtual screening. The specific chromatogram of 15 batches of Da Chaihu decoction was established by HPLC-DAD with neohesperidin as a reference. Compared with the chromatographic peaks and the reference substance, the chemical components were assigned to predict the nine components of albiflorin, paeoniflorin, naringin, hesperidin, neohesperidin, baicalin, wogonoside, saikosaponin b2, saikosaponin b1 as Q-markers of Da Chaihu decoction. Finally, the network of the "components-key targets-signal pathways-biological processes" was constructed by network pharmacology to explore the mechanism of Da Chaihu decoction in treating cholecystitis to clarify the accuracy of Q-markers. The results indicated that potential Q-markers could act on multiple targets to regulate inflammatory and metabolism, and then combine to treat cholecystitis. Q-markers could combine with the pharmacologic action of Da Chaihu decoction, which could elucidate the overall efficacy of Da Chaihu decoction. This study explored the Q-markers of Da Chaihu decoction combined with the specific chromatogram and network pharmacology, which provided a basis for the quality control and evaluation of Da Chaihu decoction.

3.
Acta Pharmaceutica Sinica ; (12): 1375-1386, 2022.
Article in Chinese | WPRIM | ID: wpr-924758

ABSTRACT

We predicted the anti-hepatitis B virus (HBV) active components and mechanism of Salvia miltiorrhiza based on network pharmacology. The active components of S. miltiorrhiza were obtained through TCMSP, PubChem database and literature research. The potential targets of the active components and HBV infection were predicted by SwissTargetPrediction and GeneCards databases, respectively. The protein-protein interaction (PPI) network was constructed by String database. Cytoscape software was adopted to construct a visual network of active component-disease target and perform topological analysis. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed using DAVID platform. The molecular docking of key components and core targets was carried out by AutoDock Vina software. We screened out a total of 38 active components and 178 disease-component overlapping targets. Enrichment analyses obtained 405 related GO items and 68 signaling pathways, such as T/B cell receptor signaling pathways, PI3K/AKT signaling pathway, and mTOR signaling pathway. According to the results of molecular docking, most characteristic components of S. miltiorrhiza (miltionone Ⅱ, miltirone, protocatechuic acid, lithospermic acid, protocatechualdehyde) showed good affinity with the key targets (PIK3CA, APP, STAT3,AKT1 and mTOR). Furthermore, the anti-HBV activity of lithospermic acid, the representative active component of S. miltiorrhiza, and its regulation on PI3K/AKT and mTOR signaling pathways were investigated in an HBV replicating mouse model. Animal welfare and experimental procedures follow the regulations of the Animal Ethics and Welfare Committee of Hubei University. The results showed that lithospermic acid significantly inhibited HBV DNA replication, reduced serum HBsAg and HBeAg levels, and decreased the phosphorylation protein expression levels of AKT and mTOR in liver, indicating that lithospermic acid might exert the anti-HBV activity by regulating PI3K/AKT and mTOR signaling pathways.

4.
Article in Chinese | WPRIM | ID: wpr-923477

ABSTRACT

Objective @#To explore the medication law and mechanism of traditional Chinese medicine compounds in the treatment of periodontal disease through data mining, network pharmacology, and molecular docking. @* Methods@#First, data mining was used to search single medicinal materials for the treatment of periodontal disease, and the active components and their action targets were screened. Second, the disease target database was employed to download the targets related to the pathogenesis of periodontal disease, map them with the action targets of traditional Chinese medicine, and obtain the targets that are considered potential targets of traditional Chinese medicine in the treatment of periodontal disease. Potential targets were analyzed for gene ontology function and signaling pathway. They were then screened to obtain the key targets for the treatment of periodontal disease. Finally, the active components were docked with key targets.@* Results@# Among the traditional Chinese medicine prescriptions for the treatment of periodontal disease, Shudihuang, Mudanpi, Danggui, Fuling, Jinyinhua, Shanyao and Zhimu had the highest frequencies. Forty-three active components and 118 action targets were screened, and 52 potential targets were obtained by intersection with 856 disease targets. The molecular functions and biological processes in which potential targets may participate mainly focus on vitamin D biosynthesis and RNA polymerase Ⅱ regulation and involve 96 signaling pathways. Through the analysis of network topology parameters, 11 key targets were obtained. The results of molecular docking showed that the active components and RAC-alpha serine/threonine-protein kinase (AKT1), cellular tumor antigen p53 (TP53), and mitogen-activated protein kinase-1 (MAPK-1) have good binding activity. @* Conclusion @#Traditional Chinese medicine compounds may play a role in the treatment of periodontal disease by inhibiting alveolar bone absorption, have antibacterial and anti-inflammatory properties, and promote tissue repair. The effective treatment of periodontal disease by traditional Chinese medicine compounds provides a more scientific reference to the sustainable development of traditional Chinese medicine.

5.
Article in Chinese | WPRIM | ID: wpr-923022

ABSTRACT

Objective To explore the mechanism of motherwort in the treatment of nerve injury. Methods The active components of motherwort were obtained by searching TCMSP and BATMAN-TCM databases. The action targets of candidate compounds were collected and predicted from TCMSP and SwissTargetPrediction (STP) databases. The target genes corresponding to the active components of motherwort were obtained by using the standardized database of disease targets (Uniprot). The potential targets of motherwort in the treatment of nerve injury were obtained by mapping the disease genes of nerve injury with the three databases of Genecards, DisGenet and OMIM. The network topology analysis software Cytoscape 3.6.0 was used to construct the action target network of motherwort active components. The protein interaction platform database (STRING) was used to construct the interaction relationship between action targets. The target protein interaction (PPI) network was constructed by introducing Cytoscape 3.6.0 software. Through STRING database, GO enrichment analysis and KEGG pathway enrichment analysis were carried out to analyze the target points of motherwort in the treatment of nerve injury. Results 19 active components were screened from motherwort, involving 654 action targets, including 426 action targets related to nerve injury and 6 key targets. These target genes were mainly involved in biological regulation, oxidative stress response and cell communication and other biological processes. Molecular functions were mainly related to protein binding, ion binding and catalytic reduction. They were enriched outside the cell membrane. Its mechanism was related to signal pathways such as MAPK, Toll-like receptor, PI3K-Akt, TNF, IL-17, and apoptosis. Conclusion The active components of motherwort may play a protective role on nerve injury through anti-inflammation, anti-apoptosis and promoting cell growth.

6.
Acta Pharmaceutica Sinica ; (12): 399-408, 2022.
Article in Chinese | WPRIM | ID: wpr-922931

ABSTRACT

To investigate the therapeutic effect and molecular mechanism of the main flavonoid components of Silybum marianum (S. marianum) on nonalcoholic fatty liver disease (NAFLD), we identified nine flavonoids in S. marianum through TCMSP, PubChem database and corresponding literatures. The potential therapeutic targets of NAFLD were predicted by SwissTargetPrediction, GeneCards and Venny 2.1.0 platform, while the protein-protein interaction (PPI) network of potential targets was analyzed using String platform and Cytoscape software. Then GO and KEGG pathway enrichment analysis were performed using David 6.8 database, followed by molecular docking verification using AutoDock software. In vitro, components with higher degree value in the "components-targets-pathway" network were chosen for further analysis. L02 cells were used to establish lipid accumulation model and treated with different components. Furthermore, the effects of four pure active compounds from S. marianum on lipid accumulation in hepatocytes were analyzed by oil red O staining. The results showed that the main nine flavonoids extracted from S. marianum contained 24 potential NAFLD targets. Several critical pathways closely related to NAFLD process were identified by GO and KEGG enrichment analysis, including phosphatidylinositol 3-kinase-protein kinase B (PI3K-Akt) pathway, type 2 diabetes pathway, tumor necrosis factor (TNF) pathway and insulin resistance pathway. The results of molecular docking further indicated that the core components displayed strong binding abilities with key targets respectively, and silandrin showed better binding activity as compared to other components. The results obtained from L02 cells showed that the lipid accumulation was reduced by treatment with isosilybin A, isosilybin B, silydianin and silychristin, while the activity of isosilybin B was better than that of isosilybin A. Taken together, we concluded that the main flavone components of S. marianum could improve lipid accumulation through multiple signaling pathway in hepatocytes, and this could be a potential new strategy for the treatment of NAFLD.

7.
Acta Pharmaceutica Sinica ; (12): 375-384, 2022.
Article in Chinese | WPRIM | ID: wpr-922926

ABSTRACT

Drug repositioning provides new clinical indications for existing drugs. The imbalance between body's "immune-inflammation" regulation is one of the important factors in the occurrence and development of diabetic nephropathy (DN). Chinese patent medicine Kunxian capsule is clinically used for treating rheumatoid arthritis with satisfying immune-modulatory and anti-inflammatory actions. Notably, accumulating clinical evidence based on small cohorts had shown that Kunxian capsule may be used to treat DN. But the underlying pharmacological mechanisms remain unclear. Therefore, this study integrated "drug target-disease gene-biological pathway-function module" multi-level associated network analysis, and in vivo and in vitro experiments, to verify the pharmacological effects of Kunxian capsules in DN and to elucidate its molecular mechanisms. The experimental protocol was reviewed by the Laboratory Animal Welfare and Ethics Committee of China Academy of Chinese Medical Sciences, and it complies with the relevant regulations on laboratory animal welfare and ethics. As a result, the network analysis showed that the candidate targets of Kunxian capsule against DN were significantly involved into various functional modules which were related to modulation of immune-inflammation system, basement membrane lesion, abnormal hemorheology, energy metabolism and hormone metabolism, and the number of targets enriched by PI3K/AKT/NF-κB pathway is the largest. In addition, both in vivo and in vitro experiments demonstrated that Kunxian capsule by gavage effectively reduced blood glucose, improved insulin resistance, reduced blood lipid, inhibited renal extracellular matrix protein production and renal inflammation, improved renal function and pathological damages, and inhibited the activity of PI3K/AKT/NF-κB/TNF-α/IL-1β pathway in diabetic nephropathy rats. Collectively, these findings suggest the therapeutic potentials of Kunxian capsule to alleviate DN by regulating the imbalance of immune-inflammation system.

8.
Acta Pharmaceutica Sinica ; (12): 716-723, 2022.
Article in Chinese | WPRIM | ID: wpr-922896

ABSTRACT

This study identified the exact molecular mechanisms of baicalein on neuroinflammation in lipopolysaccharide (LPS)-induced BV-2 cells. Bioinformatics methods and molecular docking were integrated for predicting the potential targets and mechanisms of baicalein. Immunofluorescence staining and Western blot were used to analyze the predicted key targets [inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2)], the expression level of protein related to signal transducer and activator of transcription 1/nuclear factor kappa-B (STAT1/NF-‍κB) signaling pathway and its upstream regulator NADPH oxidase-2 (NOX2), and then the mechanism of baicalein in alleviating neuroinflammation was explored. The results showed that iNOS and COX-2 were predicted as the key targets and NF-κB signaling pathway was one of the important pathways by bioinformatics methods and molecular docking. Experimental verification showed that baicalein could significantly reduce the expression of iNOS and COX-2, inhibit the phosphorylation of NF-κB and STAT1 and the production of NOX2 in LPS-induced BV-2 cells. To sum up, baicalein could effectively inhibit the inflammatory reaction in LPS-induced BV-2 cells through regulating NOX2 (gp91phox/p47phox)/STAT1/NF-κB pathway.

9.
Acta Pharmaceutica Sinica ; (12): 766-774, 2022.
Article in Chinese | WPRIM | ID: wpr-922889

ABSTRACT

Aa a characteristic medicinal plant in China, Gentiana rigescens Franch. has the function of protecting the liver and invigorating the spleen. At present, there are a few studies on the content determination method of characteristic components of G. rigescens, so it is necessary to establish a scientific and effective quality control method; In this study, The high performance liquid chromatography (HPLC) fingerprint of G. rigescens was established, based on literature reviewed and characteristic spectrum identified, the source range of G. rigescens quality marker (Q-marker) was screened. The effectiveness of the ingredients and the corresponding targets and pathways was analyzed through network pharmacology, and drew the diagram of ''component-target-pathway''. Qualitative and quantitative analysis of G. rigescens was performed by HPLC, and screen the main marker components leading to the differences between groups which were determined the Q-marker of G. rigescens; The literature and HPLC had determined that five iridoids were the main source of G. rigescens Q-marker. The network pharmacology (effectiveness) and qualitative and quantitative (detectability) analysis of G. rigescens from different producing areas confirmed that gentiopicroside, swertiamarin, and sweroside can be used as the main landmark components, and there were significant differences in their contents among different producing areas; The analysis of G. rigescens from different producing areas was carried out by network pharmacology and chemical fingerprints, it is confirmed can be used as potential Q-marker to provide sufficient theoretical basis for the quality control of G. rigescens in the later period.

10.
China Pharmacy ; (12): 293-298, 2022.
Article in Chinese | WPRIM | ID: wpr-913086

ABSTRACT

OBJ ECTIVE To predict the quality marker (Q-Marker)of Forsythia suspensa . METHODS The fingerprints of 10 batches of F. suspensa were established by high performance liquid chromatography. The common peaks were confirmed. The candidate components of Q-Marker in F. suspensa were screened. The volatile oil of F. suspensa were analyzed by gas chromatography-mass spectrometry (GC-MS),and the candidate components of Q-Marker in volatile oil were screened. The network pharmacology analysis was performed for the candidate components of Q-Marker. The network diagram of the “candidate components of F. suspensa Q-Marker-target-pathway”was constructed to predict the Q-marker of F. suspensa . RESULTS & CONCLUSIONS Twenty-one common peaks were obtained for 10 batches of F. suspensa ,and four components were identified as phillyrin,forsythoside A ,pinoresinol-4-O-β-D-glucoside and rutin. Seven candidate components were obtained by GC-MS analysis,such as β-pinene,α-pinene,terpinen-4-ol,limonene,γ-terpinene,α-phellandrene,β-myrcene. By network pharmacology analysis, 16 key targets and 17 pathways were obtained. It was preliminarily predicted that phillyrin , forsythoside A , pinoresinol-4-O-β-D-glucoside,rutin,terpinen-4-ol,α-phellandrene,α-pinene and β-pinene were Q-marker of F. suspensa .

11.
Article in Chinese | WPRIM | ID: wpr-907149

ABSTRACT

Objective To explore the potential mechanism of Erchen decoction in the treatment of obese polycystic ovary syndrome and obese infertility, in order to provide theoretical basis for “treating different diseases with same method”. Methods The active ingredients and targets of Erchen decoction were obtained from TCMSP database, and the targets of obese polycystic ovary syndromes and obese infertility were obtained from GeneCard database. Active ingredient-target network was constructed by Cytoscape 3.7.1, and protein-protein interaction network and core target were obtained from STRING. GO and KEGG enrichment analysis were performed by Cytoscape 3.7.1 and online software. Results 125 ingredients and 218 targets of Erchen decoction were obtained. There were 2 783 target genes for obese infertility and 2 962 target genes for obese polycystic ovary syndrome. Erchen decoction has a total of 117 target genes in the treatment of obese infertility and obese polycystic ovary syndromes, which proves the principle of “treating different diseases with same method”. Potential active ingredients include quercetin, kaempferol, naringin, baicalin and formononetin. PPI showed that STAT3, JUN, AKT1, MAPK3, MAPK1, MAPK14, IL-6 and FOS were the core targets of “treating different diseases with same method”. Molecular docking results showed that quercetin, kaempferol, etc. had good binding ability with JUN. GO and KEGG enrichment analysis showed that AGE-RAGE signaling pathway, IL-17 signaling pathway and endocrine resistance might be the key pathways for the “treating different diseases with same method” of Erchen decoction. Conclusion Erchen decoction treating "different diseases with same method" involves same targets and same pathways, which can provide reference for future experimental research.

12.
Acta Pharmaceutica Sinica B ; (6): 2239-2251, 2022.
Article in English | WPRIM | ID: wpr-929406

ABSTRACT

The potential medicinal value of Ma bamboo (Dendrocalamus latiflorus), one of the most popular and economically important bamboo species in China, has been underestimated. In the present study, we found that D. latiflorus leaf extract (DLE) reduced fasting blood glucose levels, body weight, and low-density lipoprotein cholesterol with low liver toxicity in db/db mice. In addition, gene expression profiling was performed and pathway enrichment analysis showed that DLE affected metabolic pathways. Importantly, DLE activated the AKT signaling pathway and reduced glucose production by downregulating glucose-6-phosphatase (G6PC) and phosphoenolpyruvate carboxykinase 1 (PCK1) expression. Moreover, network pharmacology analysis identified rutin as an active component in DLE through targeting insulin growth factor 1 receptor (IGF1R), an upstream signaling transducer of AKT. Due to its hypoglycemic effects and low toxicity, DLE may be considered an adjuvant treatment option for type 2 diabetes patients.

13.
Acta Pharmaceutica Sinica B ; (6): 890-906, 2022.
Article in English | WPRIM | ID: wpr-929333

ABSTRACT

Antrodia cinnamomea is extensively used as a traditional medicine to prevention and treatment of liver cancer. However, its comprehensive chemical fingerprint is uncertain, and the mechanisms, especially the potential therapeutic target for anti-hepatocellular carcinoma (HCC) are still unclear. Using UPLC‒Q-TOF/MS, 139 chemical components were identified in A. cinnamomea dropping pills (ACDPs). Based on these chemical components, network pharmacology demonstrated that the targets of active components were significantly enriched in the pathways in cancer, which were closely related with cell proliferation regulation. Next, HCC data was downloaded from Gene Expression Omnibus database (GEO). The Cancer Genome Atlas (TCGA) and DisGeNET were analyzed by bioinformatics, and 79 biomarkers were obtained. Furtherly, nine targets of ACDP active components were revealed, and they were significantly enriched in PI3K/AKT and cell cycle signaling pathways. The affinity between these targets and their corresponding active ingredients was predicted by molecular docking. Finally, in vivo and in vitro experiments showed that ACDPs could reduce the activity of PI3K/AKT signaling pathway and downregulate the expression of cell cycle-related proteins, contributing to the decreased growth of liver cancer. Altogether, PI3K/AKT-cell cycle appears as the significant central node in anti-liver cancer of A. Cinnamomea.

14.
Article in English | WPRIM | ID: wpr-929240

ABSTRACT

The infiltration of immune cells into the hepatocellular carcinoma microenvironment is the main reason why hepatocellular carcinoma patients are prone to carcinoma recurrence and the disease are incurable. Notably, the infiltration of Treg cells is the main trigger. Dahuang Zhechong pill (DHZCP) is a traditional Chinese herbal compound successful in the treatment of hepatitis and hepatocellular carcinoma. DHZCP can heal and nourish while slowing the onset of the disease, thereby strengthening the body's immune function. It can localize tumors and ultimately achieve the goal of eliminating tumors. In this study, an orthotopic liver cancer model of mice was used to explore the mechanism of DHZCP enhancing anti-tumor immunity, which showed more Th1 cells in the peripheral blood and spleen after DHZCP treatment, while more IFN-γ was secreted to activate CD8+ T cells and Treg cell production was inhibited, thereby suppressing the growth of HCC. Finally, we also analyzed the potential components of DHZCP from the perspective of modern targets using network pharmacology methods and experimental results.


Subject(s)
Animals , CD8-Positive T-Lymphocytes , Carcinoma, Hepatocellular/drug therapy , Drugs, Chinese Herbal , Humans , Liver Neoplasms/drug therapy , Mice , T-Lymphocytes, Regulatory , Tumor Microenvironment
15.
Article in English | WPRIM | ID: wpr-929235

ABSTRACT

Bladder cancer is the most common malignancy of the urinary system. Compound Kushen Injection (CKI) is a Chinese medicinal preparation that has been widely used in the treatment of various types of cancers in the past two decades. However, the pharmacological effect of CKI on bladder cancer is not still completely understood. In the current study, network pharmacology combined with bioinformatics was used to elucidate the therapeutic mechanism and potential targets of CKI in bladder cancer. The mechanism by which CKI was effective against bladder cancer was further verified in vitro using human bladder cancer cell line T24. Network pharmacology analysis identified 35 active compounds and 268 target genes of CKI. Bioinformatics data indicated 5500 differentially expressed genes associated with bladder cancer. Common genes of CKI and bladder cancer suggested that CKI exerted anti-bladder cancer effects by regulating genes such as MMP-9, JUN, EGFR, and ERK1. Functional enrichment analysis indicated that CKI exerted therapeutic effects on bladder cancer by regulating certain biological processes, including cell proliferation, cell migration, and cell apoptosis. In addition, Kyoto Encyclopedia of Genes and Genomes enrichment analysis implicated pathways related to cancer, bladder cancer, and the PI3K-Akt signaling pathway. Consistently, cell experiments indicated that CKI inhibited the proliferation and migration of T24 cells, and induced their apoptosis. Moreover, RT-qPCR and Western blot results demonstrated that CKI was likely to treat bladder cancer by down-regulating the gene and protein expression of MMP-9, JUN, EGFR, and ERK1. CKI inhibited the proliferation and migration, and induced the apoptosis of T24 bladder cancer cells through multiple biological pathways and targets. CKI also exhibited significant effects on the regulation of key genes and proteins associated with bladder cancer. Overall, our findings provide solid evidence and deepen current understanding of the therapeutic effects of CKI for bladder cancer, and further support its clinical use.


Subject(s)
Computational Biology , Drugs, Chinese Herbal , Humans , Network Pharmacology , Phosphatidylinositol 3-Kinases , Urinary Bladder Neoplasms/genetics
16.
Article in English | WPRIM | ID: wpr-928956

ABSTRACT

OBJECTIVE@#To investigate the pharmacodynamic material basis, mechanism of actions and targeted diseases of Salicornia europaea L. (SE) based on the network pharmacology method, and to verify the antidepressant-like effect of the SE extract by pharmacological experiments.@*METHODS@#Retrieval tools including Chinese medicine (CM), PubMed, PharmMapper, MAS 3.0 and Cytoscape were used to search the components of SE, predict its targets and related therapeutic diseases, and construct the "Component-Target-Pathway" network of SE for central nervous system (CNS) diseases. Further, protein-protein interaction (PPI) network, Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) function annotation of depression-related targets were analyzed to predict the antidepressant mechanism of SE. Chronic unpredictable mild stress (CUMS) model was used to construct a mouse model with depression-like symptoms. And the animals were randomly divided into 6 groups (n=10) including the normal group (nonstressed mice administered with distilled water), the CUMS group (CUMS mice administered with distilled water), the venlafaxine group (CUMS mice administered with venlafaxine 9.38 mg/kg), SE high-, medium-, and low-dose groups (CUMS mice administered with SE 1.8, 1.35 and 0.9 g/kg, respectively). Then some relevant indicators were determined for experimental verification by the forced swim test (FST), the tail suspension test (TST) and open-field test (OFT). Dopamine (DA) concentration in hippocampus and cerebral cortex, IL-2 and corticosterone (CORT) levels in blood, and nuclear factor E2 related factor 2 (Nrf2), kelch-like epichlorohydrin related protein 1 (Keap1), NAD(P) H dehydrogenase [quinone] 1 (NQO1) and heme oxygenase-1 (HO-1) levels in mice were measured by enzyme linked immunosorbent assay (ELISA) and Western blot respectively to explore the possible mechanisms.@*RESULTS@#The "target-disease" network diagram predicted by network pharmacology, showed that the potential target of SE involves a variety of CNS diseases, among which depression accounts for the majority. The experimental results showed that SE (1.8, 1.35 g/kg) significantly decreased the immobility period, compared with the CUMS group in FST and TST in mice after 3-week treatment, while SE exhibited no significant effect on exploratory behavior in OFT in mice. Compared with CUMS group, the SE group (0.9 g/kg) showed significant differences (P<0.05) in DA levels in the hippocampus and cerebral cortex. In addition, compared with CUMS control group, SE (1.8 g/kg) group showed a significant effect on decreasing the activities of CORT (P<0.05), and serum IL-2 level with no statistical significance. Finally, Western blot results showed that compared with the model group, Nrf2, Keap1, NQO1 and HO-1 protein expressions in SE group (1.8 g/kg) were up-regulated (all P<0.01).@*CONCLUSION@#The SE extract may have an antidepressant effect, which appeared to regulate Nrf2-ARE pathway and increased levels of DA and CORT in the hippocampus and cortex.


Subject(s)
Animals , Antidepressive Agents/therapeutic use , Behavior, Animal , Chenopodiaceae/metabolism , Depression/drug therapy , Disease Models, Animal , Hippocampus , Kelch-Like ECH-Associated Protein 1/metabolism , Mice , NF-E2-Related Factor 2/metabolism , Network Pharmacology , Plant Extracts/therapeutic use , Stress, Psychological/drug therapy
17.
Article in English | WPRIM | ID: wpr-928941

ABSTRACT

OBJECTIVE@#To study the mechanism of Chinese herbal medicine Fuzheng Kang'ai Formula (, FZKA) on tumor microenvironment (TME).@*METHODS@#CIBERSORTx was used for analysis of TME. Traditional Chinese Medicine Systems Pharmacology and Analysis Platform was applied to identify compounds-targets network and the Cancer Genome Atlas (TCGA) was employed to identify the differential expression genes (DEGs) between tumor and paracancerous tissues in lung adenocarcinoma (LUAD) from TCGA-LUAD. Additionally, DEGs with prognosis in LUAD was calculated by univariable and multivariate Cox regression. The core targets of FZKA were analyzed in lung adenocarcinoma TME. Protein-protein interaction database was employed to predict down-stream of target. Quantitative reverse transcription polymerase chain reaction was employed for biological experiment in A549, H1299 and PC9 cell lines.@*RESULTS@#The active and resting mast cells were significantly associated with prognosis of LUAD (P<0.05). Of the targets, CCNA2 as an important target of FZKA (hazard ratio=1.41, 95% confidential interval: 1.01-2.01, P<0.05) was a prognostic target and significantly associated with mast cells. CCNA2 was positively correlated with mast cell activation and negatively correlated with mast cell resting state. BCL1L2, ACTL6A and ITGAV were down-stream of CCNA2, which were validated by qRT-PCR in A549 cell.@*CONCLUSION@#FZKA could directly bind to CCNA2 and inhibit tumor growth by regulating CCNA2 downstream genes and TME of NSCLC closely related to CCNA2.


Subject(s)
Actins , Adenocarcinoma of Lung/pathology , Carcinoma, Non-Small-Cell Lung/metabolism , Chromosomal Proteins, Non-Histone , DNA-Binding Proteins , Drugs, Chinese Herbal/therapeutic use , Humans , Lung Neoplasms/metabolism , Tumor Microenvironment
18.
Article in English | WPRIM | ID: wpr-928657

ABSTRACT

To explore the mechanism of ovarian toxicity of Hook. F. (TwHF) by network pharmacology and molecular docking. The candidate toxic compounds and targets of TwHF were collected by the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) and the Comparative Toxicogenomics Database (CTD). Then, the potential ovarian toxic targets were obtained from CTD, and the target genes of ovarian toxicity of TwHF were analyzed using the STRING database. The protein-protein interaction (PPI) network was established by Cytoscape and analyzed by the cytoHubba plug-in to identify hub genes. Additionally, the target genes of ovarian toxicity of TwHF were subjected to Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses by using the R software. Finally, Discovery Studio software was used for molecular docking verification of the core toxic compounds and the hub genes. Nine candidate toxic compounds of TwHF and 56 potential ovarian toxic targets were identified in this study. Further network analysis showed that the core ovarian toxic compounds of TwHF were triptolide, kaempferol and tripterine, and the hub ovarian toxic genes included , , , , , , , , and . Besides, the GO and KEGG analysis indicated that TwHF caused ovarian toxicity through oxidative stress, reproductive system development and function, regulation of cell cycle, response to endogenous hormones and exogenous stimuli, apoptosis regulation and aging. The docking studies suggested that 3 core ovarian toxic compounds of TwHF were able to fit in the binding pocket of the 10 hub genes. TwHF may cause ovarian toxicity by acting on 10 hub genes and 140 signaling pathways.


Subject(s)
Drugs, Chinese Herbal/toxicity , Medicine, Chinese Traditional , Molecular Docking Simulation , Network Pharmacology , Protein Interaction Maps
19.
Article in English | WPRIM | ID: wpr-928653

ABSTRACT

To investigate the therapeutic effect and mechanism of Qingfei oral liquid in idiopathic pulmonary fibrosis. Seventy-two male SD rats were divided into control group, model group, pirofenidone group and Qingfei group with 18 animals in each group. The idiopathic pulmonary fibrosis was induced in last three groups by intratracheal injection of bleomycin; pirofenidone group was given oral administration of pirofenidone b.i.d for 21 d, and Qingfei group was given Qingfei oral liquid 3.6 mL/kg q.d for Lung tissues were obtained for HE staining, Masson staining and transforming growth factor (TGF)-β immunohistochemical staining. Superoxide dismutase (SOD), malondialdehyde (MDA) and glutathione (GSH) were detected in tissue homogenates. The BATMAN-TCM database was used to retrieve the chemical components and their corresponding targets of Qingfei oral solution by network pharmacology method, and then the component-target-disease network diagram was constructed. Finally, the pathway enrichment analysis was carried out to explore the molecular mechanism of Qingfei oral liquid against idiopathic fibrosis. Histopathology results showed that Qingfei oral liquid had a similar relieving effect on pulmonary fibrosis as the positive drug pirfenidone; TGF-β secretion had a significant reduction in lung tissues of Qingfei group; and Qingfei oral liquid had better regulatory effect on SOD, MDA and GSH than pirfenidone. The results of component-target-disease network and pathway enrichment analysis showed that the related molecular pathways were concentrated in inflammation, extracellular matrix and cytokines. Qingfei oral liquid has a good therapeutic effect on idiopathic pulmonary fibrosis in rats via regulation of inflammation, extracellular matrix and cytokines.


Subject(s)
Animals , Bleomycin/pharmacology , Cytokines , Drugs, Chinese Herbal , Glutathione , Idiopathic Pulmonary Fibrosis/drug therapy , Inflammation , Lung/pathology , Male , Network Pharmacology , Rats , Rats, Sprague-Dawley , Superoxide Dismutase/metabolism , Transforming Growth Factor beta/pharmacology
20.
Article in Chinese | WPRIM | ID: wpr-928175

ABSTRACT

This study aims to establish a method for analyzing the chemical constituents in Cistanches Herba by high performance liquid chromatography(HPLC) and quadrupole-time-of-flight tandem mass spectrometry(HPLC-Q-TOF-MS/MS), and to reveal the pharmacological mechanism based on network pharmacology for mining the quality markers(Q-markers) of Cistanches Herba. The chemical constituents of Cistanche deserticola and C. tubulosa were analyzed via HPLC-Q-TOF-MS/MS. The potential targets and pathways of Cistanches Herba were predicted via SwissTargetPrediction and DAVID. The compound-target-pathway-pharmacological action-efficacy network was constructed via Cytoscape. A total of 47 chemical constituents were identified, involving 95 targets and 56 signaling pathways. We preliminarily elucidated the pharmacological mechanisms of echinacoside, acteoside, isoacteoside, cistanoside F, 2'-acetylacteoside, cistanoside A, campneoside Ⅱ, salidroside, tubuloside B, 6-deoxycatalpol, 8-epi-loganic acid, ajugol, bartsioside, geniposidic acid, and pinoresinol 4-O-β-D-glucopyranoside, and predicted them to be the Q-markers of Cistanches Herba. This study identified the chemical constituents of Cistanches Herba, explained the pharmacological mechanism of the traditional efficacy of Cistanches Herba based on network pharmacology, and introduced the core concept of Q-markers to improve the quality evaluation of Cistanches Herba.


Subject(s)
Chromatography, High Pressure Liquid/methods , Cistanche , Drugs, Chinese Herbal/pharmacology , Network Pharmacology , Tandem Mass Spectrometry/methods
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