scholarly journals Antidiarrheal Effect of Sechang-Zhixie-San on Acute Diarrhea Mice and Network Pharmacology Deciphering Its Characteristics and Potential Mechanisms

2020 ◽  
Vol 2020 ◽  
pp. 1-16
Author(s):  
Zhiyong Li ◽  
Jianliang Li ◽  
Fengrong Zhang ◽  
Na Zhu ◽  
Zijun Sha ◽  
...  

Sechang-Zhixie-San (SCZX) is an ancient prescription used for pediatric diarrhea by the Yi people in China, which consists of Rodgersia sambucifolia Hemsley (known as Yantuo and abbreviated as YT) and Bentonite (BN). Now, it is also a Chinese patent medicine used in the clinic to treat infantile diarrhea. Besides evaluating the antidiarrheal effect of SCZX on diarrhea mice induced by Folium Sennae, the purpose of this study is to outline the characteristics of the antidiarrheal effect and reveal the potential mechanisms of SCZX through the analysis of the mechanism and active components of YT via network pharmacology and molecular docking, combined with the research progress of BN obtained from the literature. SCZX (3.12 and 12.48 g/kg) effectively inhibited diarrhea in mice, significantly lowering the loose stool rate (LSR), loose stool level (LSL), and loose stool index (LSI). Using network pharmacology, the “herb-compound-target-pathway-pharmacological action” network was mapped to indicate the antidiarrheal mechanism of YT. And the docking results revealed that 4 components of YT including quercetin, geranyl-1-O-α-L-arabinopyranosyl-(1 ⟶ 6)-β-D-glucopyranoside, 3α-O-(E)-p-hydroxy-cinnamoyl-olean-12-en-27-oic acid, and daucosterol showed significant docking activities with STAT3, EGFR, and SLC10A2, involving 11 pathways such as Th17 cell differentiation, Jak-STAT signaling pathway, ErbB signaling pathway, and HIF-1 signaling pathway. According to our research results and literature reports, the antidiarrheal could be summarized into five aspects: inhibiting intestinal inflammation, acting as a barrier to the intestinal mucosal, regulating water and ion transport, involving the purification of intestinal microorganisms, and intestinal transmission, which might be dependent on multiple proteins and intervention in multiple pathways.

2021 ◽  
Vol 2021 ◽  
pp. 1-9
Author(s):  
Yi-ding Yu ◽  
Yi-ping Xiu ◽  
Yang-fan Li ◽  
Juan Zhang ◽  
Yi-tao Xue ◽  
...  

Radix Astragali and Semen Lepidii (HQ-TLZ) is a commonly used herbal medicine combination for treatment of heart failure, which has a good clinical effect. However, its active components and mechanism of action are not clear, which limits its clinical application and development. In this study, we explored the mechanism of action of HQ-TLZ in the treatment of heart failure based on network pharmacology. We obtained 11 active ingredients and 109 targets from the TCMSP database and SwissTargetPrediction database. Next, we constructed the action network and carried out enrichment analysis. The results showed that HQ-TLZ treatment of heart failure is primarily achieved by regulating the insulin resistance, erbB signaling pathway, PI3K-Akt signaling pathway, and VEGF signaling pathway. After inverse targeting, molecular docking, and literature search, we determined that the equivalent molecular groups of HQ-TLZ in the treatment of heart failure were quercetin and kaempferol. Based on network pharmacology, we reveal the mechanism of action of HQ-TLZ in the treatment of heart failure to a certain extent. At the same time, we determined the composition of the equivalent molecular group. This provides a bridge for the consistency evaluation of natural herbs and molecular compounds, which is beneficial to the development of novel drugs and further research.


2021 ◽  
Author(s):  
Xiaojian Wang ◽  
Rui Wang ◽  
Ting Xu ◽  
Hongting Jin ◽  
Peijian Tong ◽  
...  

Abstract Background The lesion of marrow is a crucial factor in orthopedic diseases, which is recognized by orthopedics-traumatology expert from "Zhe-School of Chinese Medicine". The Chinese herbs of regulating marrow has been widely used to treat osteonecrosis of the femoral head (ONFH) in China, while the interaction mechanisms were still elucidated. Thus, we conducted this study to explore the underlying mechanism of the five highest-frequency Chinese herbs of regulating marrow(HF-CHRM) in the treatment of ONFH with the aid of network pharmacology(NP) and molecular docking(MD). Methods The active components and potential targets of HF-CHRM were obtained through several online databases, such as Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP), UniProt database. The gene targets related to ONFH were collected with the help of the OMIM and GeneCards disease-related databases. The "drug- component-target-disease" network and protein-protein interaction(PPI) network of the drug and disease intersecting targets were constructed by using Cytoscape software and the STRING database. R software was used for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. The MD of critical components and targets was carried out using Autodock Vina and Pymol to validate the binding affinity. Results A total of 54 active components, 1074 drug targets and 195 gene targets were obtained. There were 1219 ONFH related targets. 39 drug and disease intersection targets(representative genes: IL6, TP53, VEGFA, ESR1, IL1B) were obtained and considered potential therapeutic targets. 1619 items were obtained by the GO enrichment analysis, including 1517 biological processes, 10 cellular components and 92 molecular functions, which is mainly related to angiogenesis, bone and lipid metabolism and inflammatory reaction. The KEGG pathway enrichment analysis revealed 119 pathways, including AGE-RAGE signaling pathway, PI3K-Akt signaling pathway and IL-17 signaling pathway. MD results showed that quercetin, wogonin, and kaempferol active components had good affinity with IL6, TP53, and VEGFA core proteins. Conclusion The HF-CHRM can treat ONFH by multi-component, multi-target, and multi-pathway comprehensive action.


2021 ◽  
Author(s):  
Xuedong An ◽  
LiYun Duan ◽  
YueHong Zhang ◽  
De Jin ◽  
Shenghui Zhao ◽  
...  

Abstract BackgroundOur previous randomized, double-blind, placebo-controlled, multi-center clinical study showed that Compound Danshen Dripping Pills (CDDP) had a significant and safe effect in the treatment of diabetic retinopathy (DR), but its mechanism is still unclear, which we would explain based on network pharmacology and molecular docking.MethodThe active ingredients of CDDP (composed of Panax notoginseng, Salvia miltiorrhiza Bge., and Borneol) were searched in the TCMSP database. The validated target and Smiles number of the active ingredient are queried through the PubChem database, and the predicted target of the active ingredient is obtained through the Swisstarget Prediction database. The Drugbank, TTD, and DisGeNET databases were retrieved to obtain the related targets of DR. The core targets were obtained by the cluster analysis function of Cytoscape, and then the Protein-Protein Interaction was performed. The GO and KEGG signal pathways were enriched and clustered in David database. The potential active components and targets were docking with Autodock Vina, and the results were visualized by PyMOL.Result51 active components and 922 validation and prediction targets of CDDP, 715 targets of DR and 154 co-targets were obtained. Cluster analysis showed that there were two clusters, a total of 64 targets. Go and KEGG signal pathway enrichment analysis showed that the top 20 mainly included TNF and HIF-1 signaling pathway. In GO analysis, BP mainly includes positive regulation of smooth muscle cell proliferation and response to hypoxia, CC mainly includes extracellular space and extracellular domain, MF mainly includes protein binding and protein binding recognition. In KEGG database, the key genes in the TNF signaling pathway were TNF, NFkB and VEGF, in HIF-1 signaling pathway were the IL-6, STAT3, HIF1A and VEGF. Molecular docking results showed that all components of CDDP had a certain docking ability with TNF, NFkB, VEGF, IL-6, STAT3 and HIF1A, which of Asiatic acid and Salvianolic acid j was the strongest.Conclusion Based on the network pharmacology and molecular docking, the core active components of CDDP, mainly including Asiatic acid and Salvianolic acid j, which may play a role in regulating cell proliferation and response to inflammation and hypoxia by regulating the binding and recognition of intracellular and extracellular proteins, that is, mainly through TNF signaling pathway and HIF-1 signaling pathway.


2020 ◽  
Vol 11 ◽  
Author(s):  
Yanni Lai ◽  
Qiong Zhang ◽  
Haishan Long ◽  
Tiantian Han ◽  
Geng Li ◽  
...  

Background: Ganghuo Kanggan decoction (GHKGD) is a clinical experience prescription used for the treatment of viral pneumonia in the Lingnan area of China, and its clinical effect is remarkable. However, the mechanism of GHKGD in influenza is still unclear.Objective: To predict the active components and signaling pathway of GHKGD and to explore its therapeutic mechanism in influenza and to verified it in vivo using network pharmacology.Methods: The potential active components and therapeutic targets of GHKGD in the treatment of influenza were hypothesized through a series of network pharmacological strategies, including compound screening, target prediction and pathway enrichment analysis. Based on the target network and enrichment results, a mouse model of influenza A virus (IAV) infection was established to evaluate the therapeutic effect of GHKGD on influenza and to verify the possible molecular mechanism predicted by network pharmacology.Results: A total of 116 candidate active compounds and 17 potential targets were identified. The results of the potential target enrichment analysis suggested GHKGD may involve the RLR signaling pathway to reduce inflammation in the lungs. In vivo experiments showed that GHKGD had a protective effect on pneumonia caused by IAV-infected mice. Compared with the untreated group, the weight loss in the GHKGD group in the BALB/c mice decreased, and the inflammatory pathological changes in lung tissue were reduced (p < 0.05). The expression of NP protein and the virus titers in lung were significantly decreased (p < 0.05). The protein expression of RIG-I, NF-kB, and STAT1 and the level of MAVS and IRF3/7 mRNA were remarkably inhibited in GHKGD group (p < 0.05). After the treatment with GHKGD, the level of Th1 cytokines (IFN-γ, TNF-α, IL-2) was increased, while the expression of Th2 (IL-5, IL4) cytokines was reduced (p < 0.05).Conclusion: Through a network pharmacology strategy and in vivo experiments, the multi-target and multi-component pharmacological characteristics of GHKGD in the treatment of influenza were revealed, and regulation of the RLR signaling pathway during the anti-influenza process was confirmed. This study provides a theoretical basis for the research and development of new drugs from GHKGD.


2020 ◽  
Author(s):  
Ying Li ◽  
Guhang Wei ◽  
Zhenkun Zhuang ◽  
Mingtai Chen ◽  
Changjian Yuan ◽  
...  

Abstract BackgroundCorydalis Rhizoma(CR) showed a high efficacy for coronary heart disease (CHD). However, the interaction between the active ingredients of CR and the targets of CHD has not been unequivocally explained in previous researches. To study the active components and potential targets of Corydalis Rhizoma and to determine the mechanism underlying the exact effect of Corydalis Rhizoma on coronary heart disease, a method of network pharmacology was used.Materials and MethodsThe active components of CR and targets corresponding to each component were scanned out from Traditional Chinese medicine systems pharmacology database and analysis platform (TCMSP), and target genes of CHD were searched on GeneCards database and Online Mendelian Inheritance in Man(OMIM) database. The active components and common targets of CR and CHD were used to build the “CR-CHD” network through Cytoscape (version 3.2.1) software as well as protein-protein interaction(PPI) network on String database. Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis was executed by clusterProfiler(version 3.8) and DOSE(version 3.6) package on R platform.Results49 active ingredients and 394 relevant targets of CR and the 7173 CHD-related genes were retrieved. 40 common genes were selected for subsequent analysis. Crucial biological processes and pathways were obtained and analyzed, including DNA-binding transcription activator activity, RNA polymerase II-specific, RNA polymerase II transcription factor binding, kinase regulator activity, ubiquitin-like protein ligase binding, fluid shear stress and atherosclerosis, TNF signaling pathway, apoptosis, MAPK signaling pathway and PI3K-Akt signaling pathway.ConclusionsOverall, CR could alleviate CHD through the mechanisms predicted by network pharmacology, laying the foundation for future development of new drugs from traditional Chinese medicine on CHD.


2021 ◽  
Author(s):  
Ying-ying Zhang ◽  
Jian-xiong Ma ◽  
Yu-tian Zhu ◽  
Yi-xuan Wang ◽  
Wang-qiang Chen ◽  
...  

Abstract Polycystic ovary syndrome (PCOS) is a sort of endocrine disease associated with Reproduction. The formula of Cuscuta-Salvia has been widely used in treatment of PCOS in clinic. However, its chemical and pharmacological are still not known in detail. First, the active components of Cuscuta-Salvia were identified by UHPLC-ESI-Q-TOF-MS and screened from TCMSP database, and the disease targets were obtained from the DisGeNET and GeneCards databases. Subsequently, common targets between Cuscuta-Salvia and PCOS were obtained via a Venn diagram. Second, a protein-protein interaction (PPI) network was established. Core genes were selected using Cytoscape software plugin. Third, the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were performed for common targets using “pathview” package in R. Finally, several core targets were verified via determination of qRT-PCR and HE staining. Combined UHPLC-ESI-Q-TOF-MS analysis with network pharmacology study, 14 active components were obtained. Eighty common targets were also obtained. Ten core genes were regulated by Cuscuta-Salvia in PCOS, including IL6, AKT1, VEGFA, TP53, TNF, MAPK1, JUN, EGF, CASP3, and EGFR. GO results showed that cellular response to drug, response to oxygen levels, response lipopolysaccharide, and response to molecule of bacterial origin in biological process (BP) category; membrane, transcription regulator complex, nuclear chromatin, postsynaptic membrane, and vesicle lumen in cellular component (CC) category; DNA-binding transcription factor binding, RNA polymerase II-specific DNA-binding transcription factor binding, DNA-binding transcription activator activity, RNA polymerase II-specific, DNA-binding transcription activator activity, and cytokine receptor binding in molecular function (MF) terms. KEGG enrichment pathway mainly involves in PI3K−Akt signaling pathway, MAPK signaling pathway, cellular senescence, TNF signaling pathway, and IL-17signaling pathway. Furthermore, based on an experimental study, Cuscuta-Salvia ameliorated the pathology of ovary, live and adipose tissue. Additional, Cuscuta-Salvia increased the mRNA expression of VEGFA. Cuscuta-Salvia decreased the mRNA expression of IL6, AKT1, TP53, MAPK1, JUN, EGF, AR, LHb, CYP17a1, and CYP19a1. Our results demonstrate that Cuscuta-Salvia may provide a novel pharmacology basis in an experimental model of PCOS via the regulation of the gene expression. This study lays a basis for subsequent research and clinical application.


2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
Yi Kuan Du ◽  
Yue Xiao ◽  
Shao Min Zhong ◽  
Yi Xing Huang ◽  
Qian Wen Chen ◽  
...  

Alzheimer’s disease is a common neurodegenerative disease in the elderly. This study explored the curative effect and possible mechanism of Acori graminei rhizoma on Alzheimer’s disease. In this paper, 8 active components of Acori graminei rhizoma were collected by consulting literature and using the TCMSP database, and 272 targets were screened using the PubChem and Swiss Target Prediction databases. Introduce it into the software of Cytoscape 3.7.2 and establish the graph of “drug-active ingredient-ingredient target.” A total of 276 AD targets were obtained from OMIM, Gene Cards, and DisGeNET databases. Import the intersection targets of drugs and diseases into STRING database for enrichment analysis, and build PPI network in the Cytoscape 3.7.2 software, whose core targets involve APP, AMPK, NOS3, etc. GO analysis and KEGG analysis showed that there were 195 GO items and 30 AD-related pathways, including Alzheimer’s disease pathway, serotonin synapse, estrogen signaling pathway, dopaminergic synapse, and PI3K-Akt signaling pathway. Finally, molecular docking was carried out to verify the binding ability between Acori graminei rhizoma and core genes. Our results predict that Acori graminei rhizoma can treat AD mainly by mediating Alzheimer’s signal pathway, thus reducing the production of Aβ, inhibiting the hyperphosphorylation of tau protein, regulating neurotrophic factors, and regulating the activity of kinase to change the function of the receptor.


2020 ◽  
Author(s):  
Mengke Sheng ◽  
Xing Liu ◽  
Qingsong Qu ◽  
Xiaowen Wu ◽  
Yuyao Liao ◽  
...  

Abstract Background: Chronic cough significantly affects human health and quality of life. Studies have shown that Sanao Decoction(SAD)can clinically treat chronic cough. To investigate its mechanisms, we used the method of network pharmacology to conduct research at the molecular level.Methods: The active ingredients and their targets were screened by pharmacokinetics parameters from the traditional Chinese medicine system pharmacology analysis platform (TCMSP). The relevant targets of chronic cough were obtained from two databases: GeneCards and DrugBank. Take the intersection to get potential targets of SAD to treat chronic cough and establish the component-target regulatory network by CytoScape3.7.2 and protein-protein interaction (PPI) network by STRING 1.0. The function of the target gene and related pathways were analyzed by the Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) in the Database for Annotation, Visualization, and Integrated Discovery (DAVID). The significant pathways and their relevant targets were obtained and the target-pathway network was established by CytoScape3.7.2. Finally, molecular docking of the core active components and relevant targets was performed.Results: A total of 98 active components, 113 targets were identified. The component-target and target-pathway network of SAD and PPI network were established. Enrichment analysis of DAVID indicated that 2062 terms were in biological processes, 77 in cellular components, 142 in molecular functions and 20 significant pathways. In addition, the molecular docking showed that quercetin and luteolin had a good combination with the corresponding targets.Conclusions: It indicates that the active compounds of SAD, such as quercetin, luteolin, may act on AKT1, MAPK1, RELA, EGFR, BCL2 and regulate PI3K-Akt signaling pathway, AGE-RAGE signaling pathway in diabetic complications and Fluid shear stress and atherosclerosis pathway to exert the effects of anti-inflammatory, anti-airway remodeling, anti-oxidant stress and repair airway damage to treat chronic cough.


2021 ◽  
Vol 16 (9) ◽  
pp. 1934578X2110352
Author(s):  
Tian-Shun Wang ◽  
Xing-Pan Wu ◽  
Qiu-Yuan Jian ◽  
Yan-Fang Yang ◽  
Wu He-Zhen

Severe acute respiratory syndrome (SARS) once caused great harm in China, but now it is the coronavirus disease 2019 (COVID-19) pandemic that has become a huge threat to global health, which raises urgent demand for developing effective treatment strategies to avoid the recurrence of tragedies. Yinqiao powder, combined with modified Sangju decoction (YPCMSD), has been clinically proven to have a good therapeutic effect on COVID-19 in China. This study aimed to analyze the common mechanism of YPCMSD in the treatment of SARS and COVID-19 through network pharmacology and molecular docking and further explore the potential application value of YPCMSD in the treatment of coronavirus infections. Firstly, the active components were collected from the literature and Traditional Chinese Medicine Systems Pharmacology database platform. The COVID-19 and SARS associated targets of the active components were forecasted by the SwissTargetPrediction database and GeneCards. A protein–protein-interaction network was drawn and the core targets were obtained by selecting the targets larger than the average degree. By importing the core targets into database for annotation, visualization, and integrated discovery, enrichment analysis of gene ontology, and construction of a Kyoto Encyclopedia of genes and genomes pathway was conducted. Cytoscape 3.6.1 software was used to construct a “components–targets–pathways” network. Active components were selected to dock with acute respiratory syndrome coronavirus type 2 (SARS-COV-2) 3CL and angiotensin-converting enzyme 2 (ACE2) through Discovery Studio 2016 software. A network of “components–targets–pathways” was successfully constructed, with key targets involving mitogen-activated protein kinase 1, caspase-3 (CASP3), tumor necrosis factor (TNF), and interleukin 6. Major metabolic pathways affected were those in cancer, the hypoxia-inducible factor 1 signaling pathway, the TNF signaling pathway, the Toll-like receptor signaling pathway, and the PI3K-Akt signaling pathway. The core components, such as arctiin, scopolin, linarin, and isovitexin, showed a strong binding ability with SARS-COV-2 3CL and ACE2. We predicted that the mechanism of action of this prescription in the treatment of COVID-19 and SARS might be associated with multicomponents that bind to SARS-COV-2 3CL and ACE2, thereby regulating targets that coexpressed with them and pathways related to inflammation and the immune system.


2021 ◽  
Vol 5 (3) ◽  
Author(s):  
Feifei Lei ◽  
Mingjun Zhao ◽  
Haifang Wang ◽  
Chao Pan ◽  
Xiaoya Shi

Objective: To explore the target and mechanism of Astragalus membranaceus, poria, salvia miltiorrhiza and semen leiocarpa in the treatment of heart failure by network pharmacology. Methods: The active components of traditional Chinese medicine and the target of heart failure were screened by multi-platform, and the standard gene was transformed by Uniprot. CytoCasp 3.6.1 was used to draw the network diagram of traditional Chinese medicine - component - target. Go and KEGG analysis were performed by Metascape. Results: A total of 36 predictive target sites of Radix Astragalus, Fuling poria, Salvia miltiorrhiza and Draba nemorosa were screened for treatment of heart failure, mainly involving nerve and factor pathways: ADRB2, ADRA1B and AChE. Cancer pathway: TP53, TNF; Pathways of inflammation: IL1B, PTSG2, PTSG1; Sex hormone pathway: ESR1, AR, PGR; Others: SCN5A, HIF1A, etc. The results of GO and KEGG enrichment suggested that the treatment of heart failure with the top four drugs involved cancer pathway, calcium signaling pathway, HIF-1 signaling pathway, and involved in blood circulation, cell proliferation and other processes. Conclusion: This study combines the pharmacological studies of Chinese medicine and western medicine to reveal the mechanism of multi-target and multi-channel regulation of body balance in Chinese medicine treatment.


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