scholarly journals Network Pharmacology Analysis to Identify Phytochemicals in Traditional Chinese Medicines That May Regulate ACE2 for the Treatment of COVID-19

2020 ◽  
Vol 2020 ◽  
pp. 1-14
Author(s):  
Wenhao Niu ◽  
Feng Wu ◽  
Haiming Cui ◽  
Wenyue Cao ◽  
YuChieh Chao ◽  
...  

“Three formulas and three medicines,” which include Jinhua Qinggan granule, Lianhua Qingwen capsule/granule, Xuebijing injection, Qingfei Paidu decoction, HuaShiBaiDu formula, and XuanFeiBaiDu granule, have been proven to be effective in curbing coronavirus disease 2019 (COVID-19), according to the State Administration of Traditional Chinese Medicine. The aims of this study were to identify the active components of “Three formulas and three medicines” that can be used to treat COVID-19, determine their mechanism of action via angiotensin-converting enzyme 2 (ACE2) by integrating network pharmacological approaches, and confirm the most effective components for COVID-19 treatment or prevention. We investigated all the compounds present in the aforementioned herbal ingredients. Compounds that could downregulate the transcription factors (TFs) of ACE2 and upregulate miRNAs of ACE2 were screened via a network pharmacology approach. Hepatocyte nuclear factor 4 alpha (HNF4A), peroxisome proliferator-activated receptor gamma (PPARG), hsa-miR-2113, and hsa-miR-421 were found to regulate ACE2. Several compounds, such as quercetin, decreased ACE2 expression by regulating the aforementioned TFs or miRNAs. After comparison with the compounds present in Glycyrrhiza Radix et Rhizoma, quercetin, glabridin, and gallic acid present in the herbal formulas and medicines were found to alter ACE2 expression. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were used to search for possible molecular mechanisms of these compounds. In conclusion, traditional Chinese medicine (TCM) plays a pivotal role in the prevention and treatment of COVID-19. Quercetin, glabridin, and gallic acid, the active components of recommended TCM formulas and medicines, can inhibit COVID-19 by downregulating ACE2.

2020 ◽  
Vol 2020 ◽  
pp. 1-18
Author(s):  
Chunli Piao ◽  
Qi Zhang ◽  
De Jin ◽  
Li Wang ◽  
Cheng Tang ◽  
...  

Diabetic nephropathy (DN) is one of the most common complications of diabetes mellitus. Owing to its complicated pathogenesis, no satisfactory treatment strategies for DN are available. Milkvetch Root is a common traditional Chinese medicine (TCM) and has been extensively used to treat DN in clinical practice in China for many years. However, due to the complexity of botanical ingredients, the exact pharmacological mechanism of Milkvetch Root in treating DN has not been completely elucidated. The aim of this study was to explore the active components and potential mechanism of Milkvetch Root by using a systems pharmacology approach. First, the components and targets of Milkvetch Root were analyzed by using the Traditional Chinese Medicine Systems Pharmacology database. We found the common targets of Milkvetch Root and DN constructed a protein-protein interaction (PPI) network using STRING and screened the key targets via topological analysis. Enrichment of Gene Ontology (GO) pathways and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were analyzed. Subsequently, major hubs were identified and imported to the Database for Annotation, Visualization and Integrated Discovery for pathway enrichment analysis. The binding activity and targets of the active components of Milkvetch Root were verified by using the molecular docking software SYBYL. Finally, we found 20 active components in Milkvetch Root. Moreover, the enrichment analysis of GO and KEGG pathways suggested that AGE-RAGE signaling pathway, HIF-1 signaling pathway, PI3K-Akt signaling pathway, and TNF signaling pathway might be the key pathways for the treatment of DN; more importantly, 10 putative targets of Milkvetch Root (AKT1, VEGFA, IL-6, PPARG, CCL2, NOS3, SERPINE1, CRP, ICAM1, and SLC2A) were identified to be of great significance in regulating these biological processes and pathways. This study provides an important scientific basis for further elucidating the mechanism of Milkvetch Root in treating DN.


2020 ◽  
Vol 23 (1) ◽  
pp. 28-40
Author(s):  
Jia Li ◽  
Xinchang Qi ◽  
Yajuan Sun ◽  
Yingyu Zhang ◽  
Jiajun Chen

Aim and Objective: Effective components and the mechanism of action of Zhichan powder for the treatment of Parkinson's disease were researched at a systematic level. Materials and Methods: Screening of active components in Zhichan powder for the treatment of Parkinson's disease was conducted using the Traditional Chinese Medicine Systems Pharmacology database, and a medicine-target-disease network was established with computational network pharmacology. Results: By using network pharmacology methods, we identified 18 major active components in Zhichan powder through screening, indicating a connection between chemical components of this Traditional Chinese Medicine and Parkinson’s disease-related targets. Conclusion: The medicine-target-disease system of Zhichan powder established by network pharmacology permitted visualization of clustering and differences among chemical components in this prescription, as well as the complex mechanism of molecular activities among those effective components, relevant targets, pathways, and the disease. Thus, our results provide a new perspective and method for revealing the mechanism of action of Traditional Chinese Medicine prescriptions.


2019 ◽  
Vol 14 (1) ◽  
Author(s):  
Chun-Li Piao ◽  
Jin-Li Luo ◽  
De Jin ◽  
Cheng Tang ◽  
Li Wang ◽  
...  

Abstract Introduction Radix Salviae (Dan-shen in pinyin), a classic Chinese herb, has been extensively used to treat diabetic retinopathy in clinical practice in China for many years. However, the pharmacological mechanisms of Radix Salviae remain vague. The aim of this study was to decrypt the underlying mechanisms of Radix Salviae in the treatment of diabetic retinopathy using a systems pharmacology approach. Methods A network pharmacology-based strategy was proposed to elucidate the underlying multi-component, multi-target, and multi-pathway mode of action of Radix Salviae against diabetic retinopathy. First, we collected putative targets of Radix Salviae based on the Traditional Chinese Medicine System Pharmacology database and a network of the interactions among the putative targets of Radix Salviae and known therapeutic targets of diabetic retinopathy was built. Then, two topological parameters, “degree” and “closeness certainty” were calculated to identify the major targets in the network. Furthermore, the major hubs were imported to the Database for Annotation, Visualization and Integrated Discovery to perform a pathway enrichment analysis. Results A total of 130 nodes, including 18 putative targets of Radix Salviae, were observed to be major hubs in terms of topological importance. The results of pathway enrichment analysis indicated that putative targets of Radix Salviae mostly participated in various pathways associated with angiogenesis, protein metabolism, inflammatory response, apoptosis, and cell proliferation. The putative targets of Radix Salviae (vascular endothelial growth factor, matrix metalloproteinases, plasminogen, insulin-like growth factor-1, and cyclooxygenase-2) were recognized as active factors involved in the main biological functions of treatment, which implied that these were involved in the underlying mechanisms of Radix Salviae on diabetic retinopathy. Conclusions Radix Salviae could alleviate diabetic retinopathy via the molecular mechanisms predicted by network pharmacology. This research demonstrates that the network pharmacology approach can be an effective tool to reveal the mechanisms of traditional Chinese medicine from a holistic perspective.


2020 ◽  
Vol 2020 ◽  
pp. 1-12
Author(s):  
Qian Wang ◽  
Yan Liang ◽  
Can Peng ◽  
Peng Jiang

Hepatocellular carcinoma (HCC) is a malignant tumor without effective therapeutic drugs for most patients in advanced stages. Scutellariae Radix (SR) is a well-known anti-inflammatory and anticarcinogenic herbal medicine. However, the mechanism of SR against HCC remains to be clarified. In the present study, network pharmacology was utilized to characterize the mechanism of SR on HCC. The active components of SR and their targets were collected from the traditional Chinese medicine systems pharmacology database and the traditional Chinese medicine integrated database. HCC-related targets were acquired from the liver cancer databases OncoDB.HCC and Liverome. The gene ontology and the Kyoto Encyclopedia of Genes and Genomes pathway were analyzed using the Database for Annotation, Visualization, and Integrated Discovery. Component-component target and protein-protein interaction networks were set up. A total of 143 components of SR were identified, and 37 of them were considered as candidate active components. Fifty targets corresponding to 29 components of SR were mapped with targets of HCC. Functional enrichment analysis indicated that SR exerted an antihepatocarcinoma effect by regulating pathways in cancer, hepatitis B, viral carcinogenesis, and PI3K-Akt signaling. The holistic approach of network pharmacology can provide novel insights into the mechanistic study and therapeutic drug development of SR for HCC treatment.


2021 ◽  
Vol 16 ◽  
Author(s):  
Xiaolei Ma ◽  
Yinan Lu ◽  
Yang Lu ◽  
Zhili Pei

Background: Tufuling Qiwei Tangsan (TQTS) is a commonly used Mongolian medicine preparation against psoriasis in China. However, its mechanism of action and molecular targets for the treatment of psoriasis is still unclear. Network pharmacology can reveal the synergistic mechanism of drugs at the molecular, target and pathway levels, and is suitable for the complex study of traditional Chinese medicine formulations. However, it is rarely involved in the application of Mongolian medicine with the same holistic concept of traditional Chinese medicine. Method: In this paper, the active compounds of TQTS were collected and their targets were identified. Psoriasis-related targets were obtained by analyzing the differential expressed genes between psoriasis patients and healthy individuals. Then, the network concerning the interactions of potential targets of TQTS with well-known psoriasis-related targets was built. The core targets were selected according to topological parameters. And the enrichment analysis was carried out to explore the mechanism of action of TQTS. Moreover, molecular docking was performed to study the interaction between the selected ligands and receptors related to psoriasis. Result and Conclusion: Eighty-five active compounds of TQTS were screened, with corresponding 270 targets, and 313 differentially expressed genes were identified. Additionally, enrichment analysis showed that the targets of TQTS for treating psoriasis were mainly concentrated in multiple biological processes, including apoptosis, growth factor response,etc., and related pathways including PI3K-Akt and MAPK signaling pathway, and so on. Genes such as NFKB1, TP53 and MAPK1 are the key genes in the gene pathway network of TQTS against psoriasis. The 4 main active components of TQTS have certain binding activity with 13 potential targets, and the stability of interaction with AKT1 is the best, which indicate the potential mechanism of TQTS on psoriasis.


2021 ◽  
Vol 43 (1) ◽  
pp. 65-78
Author(s):  
Zhaowei Zhai ◽  
Xinru Tao ◽  
Mohammad Murtaza Alami ◽  
Shaohua Shu ◽  
Xuekui Wang

Hypertension is a cardiovascular disease that causes great harm to health and life, affecting the function of important organs and accompanied by a variety of secondary diseases, which need to be treated with drugs for a long time. P. ternata alone or combination with western medicine has played an important role in traditional Chinese medicine. Although P. ternata is used clinically to treat hypertension, its functional molecular mechanism and pharmacological mechanism have not been elucidated. Therefore, in this study, the potentially effective components, and targets of P. ternata in the treatment of hypertension were screened by the method of network pharmacology, and the mechanism of P. ternata in the treatment of hypertension was analyzed by constructing a component-target relationship network, PPI interaction network, targets’ function analysis, and molecular docking. In the study, 12 potentially effective components and 88 targets were screened, and 3 potential protein modules were found and analyzed after constructing a PPI network using targets. In addition, 10 targets were selected as core targets of the PPI network. After that, the targets were analyzed by Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. Finally, the molecular docking method is used to study the interaction between the targets and the active components. The above evidence shows that the mechanism of P. ternata in the treatment of hypertension is complicated, as it acts in many ways, mainly by affecting nerve signal transmission, cell proliferation, and apoptosis, calcium channels, and so on. The binding between targets and active components mainly depends on Pi bonds and hydrogen bonds. Using the method of network pharmacology and molecular docking to analyze the mechanism of P. ternata in the treatment of hypertension will help to provide a better scientific basis for the combined use of traditional Chinese medicine and western medicine, and will better help to improve the quality of P. ternata and point out its direction.


2021 ◽  
Vol 41 (1) ◽  
Author(s):  
Bin Liu ◽  
Xin Zheng ◽  
Jiajun Li ◽  
Xiong Li ◽  
Ruimei Wu ◽  
...  

Abstract Objective: The traditional Chinese medicine Caulis Sargentodoxae is widely used in the treatment of ulcerative colitis (UC), but the mechanism remains unknown. The present study aims to reveal its effective components, targets and pathways through network pharmacology and bioinformatics approaches. Materials and methods: Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) was used to identify effective components. The ligand-based targets prediction was achieved through SwissTargetPrediction and TargetNet. UC-related targets were identified using Gene Expression Omnibus (GEO) data and DisGeNET. The common targets of disease and components were constructed and analyzed by PPI network. Lastly, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses are used to explain the functions of these common targets. Components-Targets-Pathways network was visualized and analyzed to further reveal the connection between the components and targets. Results: Eight active components and 102 key targets were identified to play an important role in UC. These targets were related to regulation of protein serine/threonine kinase activity, positive regulation of cell motility, response to molecule of bacterial origin, response to toxic substance, ERK1 and ERK2 cascade, peptidyl-tyrosine modification, inositol lipid-mediated signaling, cellular response to drug, regulation of inflammatory response and leukocyte migration. Moreover, HIF-1 signaling pathway and PI3K-Akt signaling pathway were the key targets involved in UC-related signaling pathways. Conclusion: The eight active components of Caulis Sargentodoxae mainly play a therapeutic role for UC through synergistic regulation of HIF-1 signaling pathway and PI3K-Akt signaling pathway.


2020 ◽  
Author(s):  
Xiaolin Zhang ◽  
Di Cao ◽  
Qi Zhang ◽  
Dehui Ma ◽  
Mingjun Liu

Abstract Background: In this study, network pharmacology method was used to systematically predict and analyze the mechanism of "Common treatment for different diseases" effect of Dachaihu Decoction(DCHD) in the treatment of Prediabetes(PD) and Acute hemorrhagic stroke(AHS).Methods: TCMsp (Traditional Chinese Medicine systems pharmacology database and analysis platform) database was used to collect all the candidate active components related to 8 kinds of traditional Chinese medicine of DCHD, and UniProt database was used to obtain the drug action target and construct the "traditional Chinese medicine -Compound -target" action network; Genecards, OMIM(Online Mendelian Inheritance in Man), DisGeNET, CTD(Comparative Toxicogenomics Database) and TTD(Therapeutic Target Database)databases were used to obtain the related genes of PD and AHS respectively, and the interaction analysis of Venn with potential active components was carried out to obtain the common target of DCHD in the treatment of the two diseases.Using STRING 11.0 and Cytoscape3.72 to analyze protein-protein interaction of common targets and screen key common targets. BioGPS was used to obtain the distribution information in organs and tissues, and the relationship between the molecules and the key functional molecules were described. Bioconductor (R) was used to analyze the gene ontology (go) enrichment and the pathway analysis of the Kyoto Encyclopedia of genes and genomes (KEGG), so as to systematically predict the mechanism of "Common treatment for different diseases" of DCHD for PD and AHS.Results: with OB ≥ 30% and DL ≥ 0.18 as the screening criteria, 133 active compounds were screened out and 1034 drug targets were obtained; There are 3878 PD gene targets, 2674 AHS gene targets, 129 drug disease common targets, and 10 key targets whose median value is greater than 18;The key common targets displayed by biogps are mainly distributed in CD33+_ Myeloid.2(degree = 4),Prostate.2(degree = 3),CD56+_ NKCells.1(degree = 3),Lung.2(degree = 3),CD56+_ Nkcells. 2 (degree = 2);2281 biological processes, 65 cell components and 142 molecular functions were obtained by GO functional enrichment analysis;161 signal pathways were obtained by KEGG enrichment analysis, and the ones with higher proportion were AGE-RAGE signaling pathway in diabetic complications,PI3K-Akt signaling pathway,TNF signaling pathway,IL-17 signaling pathway,MAPK signaling pathway,HIF-1 signaling pathway,Relaxin signaling pathwa,C-type lectin receptor signaling pathway,which is mainly related to oxidative stress, glycolipid metabolism, immune inflammatory response, and neuroendocrine.Conclusion: DCHD can achieve the effect of "Common treatment for different diseases" by acting on the common receptor of PD and AHS through multi-component, multi-target and multi-channel, providing reference for further experimental verification, potential pharmacological mechanism and clinical application.


2021 ◽  
Vol 2021 ◽  
pp. 1-10
Author(s):  
Asi He ◽  
Wei Wang ◽  
Yang Xia ◽  
Xiaoping Niu

Background. As a traditional Chinese medicine, Artemisiae scopariae Herba (ASH) is used to treat various liver diseases. The purpose of this study was to explore the mechanisms of ASH for treating chronic hepatitis B (CHB) using a network pharmacological method. Methods. Bioactive ingredients and related targets of ASH were obtained from Traditional Chinese Medicine Systems Pharmacology (TCMSP) database. Gene names of targets were extracted from UniProt database. Differentially expressed genes (DEGs) of CHB were obtained from microarray dataset GSE83148. The intersect genes between DEGs and target genes were annotated using clusterProfiler package. The STRING database was used to obtain a network of protein-protein interactions. Cytoscape 3.7.2 was used to construct the “ingredient-gene-pathway” (IGP) network. Molecular docking studies were performed using Autodock vina. Results. A total of 13 active components were extracted from TCMSP database. Fifteen intersect genes were obtained between 183 target genes and 403 DEGs of GSE83148. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis results showed that ASH against CHB mainly involved in toll-like receptor signaling pathway, cellular senescence, hepatitis B, and chemokine signaling pathway. We screened one hub compound, five core targets, and four key pathways from constructed networks. The docking results indicated the strong binding activity between quercetin and AKT1. Conclusions. This study provides potential molecular mechanisms of ASH against CHB based on exploration of network pharmacology.


2021 ◽  
Vol 16 (1) ◽  
pp. 1934578X2098842
Author(s):  
Li Cheng ◽  
Fei Wang ◽  
Shun Bo Zhang ◽  
Qiu Yun You

Purpose Fufang Banlangen Keli (FBK) has been recommended for its clinical treatment of Coronavirus disease 2019 (COVID-19) and severe acute respiratory syndrome (SARS), but the mechanism of action is unclear. So, using network pharmacology and molecular docking, we studied the active components and mechanism of FBK in the treatment of COVID-19 and SARS. Methods The Encyclopedia of Traditional Chinese Medicine and Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform were used to screen the active components by oral bioactivity and drug likeness. Then, PharmMapper and SwissTargetPrediction databases were used to screen potential target genes of active components; the related target genes of COVID-19 and SARS were obtained from the GeneCards database. The intersection of the active components and disease-related targets was performed by the Venny2.1.0 database. The DAVID6.8 database and KOBAS3.0 database were used to get gene ontology (GO) function enrichment and Kyoto Encyclopedia of Genes and Genomes pathway annotation of gene targets. The “components-targets-pathways (C-T-P)” network of FBK was conducted by Cytoscape3.6.1 software. The top active components, angiotensin-converting enzyme 2 (ACE2) and SARS-CoV-2 3 Cl, were imported into AutoDock and PyMOL for molecular docking. Results From the FBK, a total of 28 active components and 73 gene targets were screened through network pharmacology. Twenty pathways were analyzed, including pathways in cancer, nod-like receptor signaling pathway, and pancreatic cancer, etc. ( P < 0.05). A total of 337 items were obtained by GO functional enrichment analysis ( P < 0.05), including 257 items for biological process, 38 items for cell composition, and 42 items for molecular function. Furthermore, molecular docking studies were performed to study potential binding between the key gene targets and selected active components. Conclusion Based on network pharmacology and molecular docking technology, qingdainone, (2Z)-2-(2-oxoindolin-3-ylidene) indolin-3-one, sinensetin, and acacetin in FBK were verified to bind to ACE2 and SARS-COV-2 3 Cl, so as to treat COVID-19 and SARS.


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