scholarly journals Uncovering the Mechanism of Astragalus membranaceus in the Treatment of Diabetic Nephropathy Based on Network Pharmacology

2020 ◽  
Vol 2020 ◽  
pp. 1-13 ◽  
Author(s):  
Ming-Fei Guo ◽  
Ya-Ji Dai ◽  
Jia-Rong Gao ◽  
Pei-Jie Chen

Background. Diabetic nephropathy (DN), characterized by hyperglycemia, hypertension, proteinuria, and edema, is a unique microvascular complication of diabetes. Traditional Chinese medicine (TCM) Astragalus membranaceus (AM) has been widely used for DN in China while the pharmacological mechanisms are still unclear. This work is aimed at undertaking a network pharmacology analysis to reveal the mechanism of the effects of AM in DN. Materials and Methods. In this study, chemical constituents of AM were obtained via Traditional Chinese Medicine Systems Pharmacology Database (TCMSP), and the potential targets of AM were identified using the Therapeutic Target Database (TTD). DisGeNET and GeneCards databases were used to collect DN-related target genes. DN-AM common target protein interaction network was established by using the STRING database. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were carried out to further explore the DN mechanism and therapeutic effect of AM. The network diagrams of the active component-action target and protein-protein interaction (PPI) networks were constructed using Cytoscape software. Results. A total of 16 active ingredients contained and 78 putative identified target genes were screened from AM, of which 42 overlapped with the targets of DN and were considered potential therapeutic targets. The analysis of the network results showed that the AM activity of component quercetin, formononetin, calycosin, 7-O-methylisomucronulatol, and quercetin have a good binding activity with top ten screened targets, such as VEGFA, TNF, IL-6, MAPK, CCL3, NOS3, PTGS2, IL-1β, JUN, and EGFR. GO and KEGG analyses revealed that these targets were associated with inflammatory response, angiogenesis, oxidative stress reaction, rheumatoid arthritis, and other biological process. Conclusions. This study demonstrated the multicomponent, multitarget, and multichannel characteristics of AM, which provided a novel approach for further research of the mechanism of AM in the treatment of DN.

2020 ◽  
Vol 2020 ◽  
pp. 1-9 ◽  
Author(s):  
Jiayan Wu ◽  
Shengkun Hong ◽  
Xiankuan Xie ◽  
Wangmi Liu

Objective. Dipsaci Radix (DR) has been used to treat fracture and osteoporosis. Recent reports have shown that myeloid cells from bone marrow can promote the proliferation of lung cancer. However, the action and mechanism of DR has not been well defined in lung cancer. The aim of the present study was to define molecular mechanisms of DR as a potential therapeutic approach to treat lung cancer. Methods. Active compounds of DR with oral bioavailability ≥30% and drug-likeness index ≥0.18 were obtained from the traditional Chinese medicine systems pharmacology database and analysis platform. The potential target genes of the active compounds and bone were identified by PharmMapper and GeneCards, respectively. The compound-target network and protein-protein interaction network were built by Cytoscape software and Search Tool for the Retrieval of Interacting Genes webserver, respectively. GO analysis and pathway enrichment analysis were performed using R software. Results. Our study demonstrated that DR had 6 active compounds, including gentisin, sitosterol, Sylvestroside III, 3,5-Di-O-caffeoylquinic acid, cauloside A, and japonine. There were 254 target genes related to these active compounds as well as to bone. SRC, AKT1, and GRB2 were the top 3 hub genes. Metabolisms and signaling pathways associated with these hub genes were significantly enriched. Conclusions. This study indicated that DR could exhibit the anti-lung cancer effect by affecting multiple targets and multiple pathways. It reflects the traditional Chinese medicine characterized by multicomponents and multitargets. DR could be considered as a candidate for clinical anticancer therapy by regulating bone physiological functions.


2019 ◽  
Vol 2019 ◽  
pp. 1-15 ◽  
Author(s):  
Jiewen Zhou ◽  
Qiuyan Wang ◽  
Zhinan Xiang ◽  
Qilin Tong ◽  
Jun Pan ◽  
...  

Xiao Ke Yin Shui (XKYS) formula is a traditional Chinese medicine formula treating type 2 diabetes mellitus (T2DM). XKYS formula consists of four herbs, i.e., Coptidis rhizoma, Liriopes radix, bitter melon, and Cassiae semen. Herein, the chemical profiles of four herb extracts were investigated, and further analysis of the underlying mechanism of XKYS formula treating T2DM was performed using network pharmacology. The main components were selected for our network-based research. Targets of XKYS formula were mainly collected from two databases, SwissTargetPrediction and Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), and the text-mining method was also implemented. T2DM relating genes and therapeutic targets were collected from five databases. Subsequently, STRING and Cytoscape were employed for the analysis of protein-protein interaction (PPI) networks. Functional annotation and pathway analysis were conducted to investigate the functions and relating pathways of target genes. The content of 12 compounds in the herb extracts was determined. With the analysis of PPI networks, a total of 76 genes were found to be important nodes and could be defined as the main target genes regulated by XKYS formula in the treatment of T2DM and its complications. Components in XKYS formula mainly regulate proteins including protein kinase B (Akt), phosphatidylinositol 3-kinase (PI3K), insulin receptor substrate (IRS), and tumor necrosis factor (TNF). XKYS formula exerts therapeutic effects in a synergetic manner and exhibits antidiabetic effect mainly via reducing insulin resistance. These findings could be guidelines in the further investigation of this formula.


2020 ◽  
Author(s):  
Li-ying Jia ◽  
Jia Li ◽  
Gui-yun Cao ◽  
Zhao-qing Meng ◽  
Lu Gan ◽  
...  

Abstract Background SheXiang XinTongNing, a commercially available Chinese patent medicine, has been widely used in the treatment of coronary heart disease. However, the mechanisms of SheXiang XinTongNing are still unclear. The aim of this study was to investigate the pharmacological mechanisms of SheXiang XinTongNing against coronary heart disease via network analysis. Method The traditional Chinese medicine system pharmacology analysis platform was used to screen the potential active constituents of the six traditional Chinese medicines in SheXiang XinTongNing, and the potential targets were obtained from PharmMapper. The genome annotation database platform was used to screen the candidate targets related to coronary heart disease. Then the drug-components-targets network and protein interaction network were built by Cytoscape 3.6.0 software. Further, GO bio-functional enrichment analysis and KEGG pathway enrichment analysis were performed through annotation, visualization and integrated discovery database. Results Results showed that the drugs-components-targets network contains 104 targets and 62 key components. The protein interaction network consisted of 107 nodes; key targets included Bcl2l1, IGF1, SRC, CASP3, et al. Functionally, the candidate targets were significantly associated with multiple pathways such as PI3K-Akt signaling pathway, MAPK signaling pathway, Ras signaling pathway, FoxO signaling pathway, Endocrine resistance. Given the above, the pharmacological activities of SheXiang XinTongNing may be predominantly related to several factors such as cell apoptosis, inflammation and angiogenesis. Conclusion XTN can effectively attenuate the symptoms of coronary heart disease through diverse pathways. The research proves that network pharmacology can successfully reveal the mechanisms of traditional Chinese medicine in a holistic view. Our systematic analysis lays a foundation for further studying.


2020 ◽  
Vol 2020 ◽  
pp. 1-11
Author(s):  
Yujie Zhang ◽  
Xiaolin Zhang ◽  
Xi Zhang ◽  
Yi Cai ◽  
Minghui Cheng ◽  
...  

Background. Atrial fibrillation (AF) is the most common sustained arrhythmia and is associated with high rates of mortality and morbidity. The traditional Chinese medicine Wenxin Keli (WXKL) can effectively improve clinical symptoms and is safe for the treatment of AF. However, the active substances in WXKL and the molecular mechanisms underlying its effects on AF remain unclear. In this study, the bioactive compounds in WXKL, as well as their molecular targets and associated pathways, were evaluated by systems pharmacology. Materials and Methods. Chemical constituents and potential targets of WXKL were obtained via the Traditional Chinese Medicine Systems Pharmacology (TCMSP). The TTD, DrugBank, DisGeNET, and GeneCards databases were used to collect AF-related target genes. Based on common targets related to both AF and WXKL, a protein interaction network was generated using the STRING database. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGGs) pathway enrichment analyses were performed. Network diagrams of the active component-target and protein-protein interactions (PPIs) were constructed using Cytoscape. Results. A total of 30 active ingredients in WXKL and 219 putative target genes were screened, including 83 genes identified as therapeutic targets in AF; these overlapping genes were considered candidate targets for subsequent analyses. The effect of treating AF was mainly correlated with the regulation of target proteins, such as IL-6, TNF, AKT1, VEGFA, CXCL8, TP53, CCL2, MMP9, CASP3, and NOS3. GO and KEGG analyses revealed that these targets are associated with the inflammatory response, oxidative stress reaction, immune regulation, cardiac energy metabolism, serotonergic synapse, and other pathways. Conclusions. This study demonstrated the multicomponent, multitarget, and multichannel characteristics of WXKL, providing a basis for further studies of the mechanism underlying the beneficial effects of WXKL in AF.


2021 ◽  
Vol 2021 ◽  
pp. 1-10
Author(s):  
Minglong Guan ◽  
Lan Guo ◽  
Hengli Ma ◽  
Huimei Wu ◽  
Xiaoyun Fan

Rosmarinic acid (RosA) is a natural phenolic acid compound, which is mainly extracted from Labiatae and Arnebia. At present, there is no systematic analysis of its mechanism. Therefore, we used the method of network pharmacology to analyze the mechanism of RosA. In our study, PubChem database was used to search for the chemical formula and the Chemical Abstracts Service (CAS) number of RosA. Then, the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) was used to evaluate the pharmacodynamics of RosA, and the Comparative Toxicogenomics Database (CTD) was used to identify the potential target genes of RosA. In addition, the Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis of target genes were carried out by using the web-based gene set analysis toolkit (WebGestalt). At the same time, we uploaded the targets to the STRING database to obtain the protein interaction network. Then, we carried out a molecular docking about targets and RosA. Finally, we used Cytoscape to establish a visual protein-protein interaction network and drug-target-pathway network and analyze these networks. Our data showed that RosA has good biological activity and drug utilization. There are 55 target genes that have been identified. Then, the bioinformatics analysis and network analysis found that these target genes are closely related to inflammatory response, tumor occurrence and development, and other biological processes. These results demonstrated that RosA can act on a variety of proteins and pathways to form a systematic pharmacological network, which has good value in drug development and utilization.


2021 ◽  
Author(s):  
qiu tiantian ◽  
Li DongHua ◽  
Liu Yu ◽  
Gao LiFang ◽  
Wei Chao ◽  
...  

Abstract Backgroud: Uterine fibroids (ULs) are the most common benign tumors of the reproductive tract in gynecology and their clinical presentations include menorrhagia, pelvic pressure, dysmenorrhea, and anemia. Surgical resection and the hormonal drug administration are the primary treatment. The plant Astragalus membranaceus (astragalus) has a long history of use in traditional Chinese medicine and studies have shown that it has antitumor effects. However, the role and mechanism of astragalus in ULs are not completely clear. The present study aimed to investigate the astragalus mechanism of action against ULs based on network pharmacology approach, in order to provid insights for the development of a safe and effective drug for the ULs treatment.Methods: The astragalus active ingredients and the potential drug targets were screened by the Traditional Chinese Medicine System Pharmacology Database and Analytical Platform (TCMSP). The gene expression profiles of ULs were obtained from Gene Expression Omnibus (GEO). The intersection of astragalus components target genes and differentially expressed genes between UL and normal patients were obtained using Perl software to provide the astragalus-ULs drug regulatory network. The protein–protein interaction (PPI) network was established using the STRING online database and Cytoscape software, followed by the topological properties analysis of the PPI networks. GO (Gene ontology) and KEGG (Kyoto Encyclopedia of Genes and Genomes) enrichment analyses were conducted by R software. The KEGG relational network was constructed using Cytoscape software. Results: A total of 21 astragalus active ingredients and 406 drug targets were obtained from the TCMSP. Seventeen of these targets overlap with ULs disease targets and were considered potential targets for the ULs treatment by astragalus. The analysis of the regulatory network showed that the astragalus active components with the most targets are quercetin, kaempferol, mangiferin, tetrodotoxin and isorhamnetin. Target genes with the highest Dgree values obtained from the PPI network analysis are estrogen receptor 1 (ESR1), tumor suppressor factor p53 (TP53), neurotrophic tyrosine kinase receptor 1 (NTRK1) and E3 ubiquitin ligase protein (CUL3). GO and KEGG enrichment analyses indicate that these targets are mainly involved in biological processes related to cellular response to reactive oxygen species, oxidative stress and response to lipopolysaccharides. The main signal transduction pathways involved include the IL-17 and TNF signaling pathways, the AGE-RAGE signaling pathway in diabetic complications and proteoglycans in cancer.Conclusions: The present study demonstrates that the astragalus therapeutic use against ULs have multicomponent and multi-target properties, providing a novel approach to further investigate the astragalus mechanism of action in the treatment of ULs.


2021 ◽  
Vol 2021 ◽  
pp. 1-15
Author(s):  
Jian Xiong Ma ◽  
Miaoyong Ye ◽  
Ke Ma ◽  
Kang Zhou ◽  
Yingying Zhang ◽  
...  

Background. Polycystic ovary syndrome (PCOS) causes low fertility in females. Coptis chinensis (C. chinensis) is used to clear heat and dampness, purify fire, and detoxify in traditional Chinese medicine (TCM). Although C. chinensis has demonstrated efficacy against PCOS in clinical practice, there are no available data regarding the bioactive components of C. chinensis, their targets, and molecular mechanisms underlying their effects. Methods and Results. Network pharmacology was used to analyze the bioactive components of C. chinensis, their targets, and signaling pathways underlying their effects. The TCM systems pharmacology database and analysis platform (TCMSP) was used to screen 14 effective active ingredients and 218 targets of C. chinensis. The GeneCards, OMIM, and PharmGkb databases were used to screen 3517 disease targets for PCOS, and 102 common targets of drugs and diseases were screened using R Cytoscape that was utilized to build a drug-active ingredient-disease target interaction network, and the STRING platform was utilized to construct a common target protein-protein interaction network, including 102 nodes and 221 edges. Key targets of C. chinensis for the treatment of PCOS included JUN, MAPK, IL6, CXCL8, FOS, and IL1B. A total of 123 gene ontology (GO) terms and 129 pathways were acquired by GO and KEGG enrichment analyses. The AGEs/RAGE, TNF, IL-17, MAPK, and HIF-1 signaling pathways were closely related to PCOS and may be the core pathways involved in PCOS. Schrodinger software was used to evaluate the interaction between active components and their targets and explore binding modes. Furthermore, based on the prediction of network pharmacology study, a mouse model of PCOS was established to evaluate the curative role and underlying mechanisms of C. chinensis. The results showed that C. chinensis treatment reversed histopathological damage of the ovary and also ameliorated the mRNA and protein expression levels of the predicted hub targets (MAPK1, CXCL8, IL-6, and IL-1β). These results indicated that WZYZP has a protective effect on spermatogenesis disorder, suggesting that it could be an alternative choice for male infertility therapy. Conclusions. This preliminary study verified the basic pharmacological effects and mechanisms of C. chinensis, a TCM, in the treatment of PCOS. These results indicate that the therapeutic effects of C. chinensis on PCOS may be achieved by regulating the expression of inflammatory factors. This study provides new insights for the systematic exploration of the mechanism of traditional Chinese medicine.


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 2020 ◽  
pp. 1-11
Author(s):  
Qi Jin ◽  
Xiao-Feng Hao ◽  
Li-Ke Xie ◽  
Jing Xu ◽  
Mei Sun ◽  
...  

Background. Diabetic retinopathy (DR) includes a series of typical lesions affected by retinal microvascular damage caused by diabetes mellitus (DM), which not only seriously damages the vision, affecting the life’s quality of patients, but also brings a considerable burden to the family and society. Astragalus Membranaceus (AM) is a commonly used medicine in clinical therapy of eye disorders in traditional Chinese medicine (TCM). In recent years, it is also used for treating DR, but the specific mechanism is unclear. Therefore, this study explores the potential mechanism of AM in DR treatment by using network pharmacology. Methods. Based on the oral bioavailability (OB) and drug likeness (DL) of two ADME (absorption, distribution, metabolism, excretion) parameters, Traditional Chinese Medicine Systems Pharmacology Database (TCMSP), Swiss Target Prediction platform, GeneCards, and OMIM database were used to predict and screen the active compounds of AM, the core targets of AM in DR treatment. The Metascape data platform was used to perform Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis on the core targets. Results. 24 active compounds were obtained, such as quercetin, kaempferol, and astragaloside IV. There were 169 effective targets of AM in DR treatment, and the targets were further screened and finally, 38 core targets were obtained, such as VEGFA, AKT1, and IL-6. EGFR tyrosine kinase inhibitor resistance, AGE-RAGE signaling pathway in diabetic complications, PI3K-Akt signaling pathway, and other metabolic pathways participated in oxidative stress, cell apoptosis, angiogenesis signal transduction, inflammation, and other biological processes. Conclusion. AM treats DR through multiple compounds, multiple targets, and multiple pathways. AM may play a role in the treatment of DR by targeting VEGFA, AKT1, and IL-6 and participating in oxidative stress, angiogenesis, and inflammation.


2020 ◽  
Vol 2020 ◽  
pp. 1-8
Author(s):  
Junmin Chen ◽  
Jianyong Chen ◽  
Jingrong Lu

Oroxylum indicum (O. indicum) is an important traditional Chinese medicine that exerts a wide spectrum of pharmacological activities. However, the pharmacological effect of O. indicum and its mechanism of action have not to be systematically elucidated yet. In this study, the druggability for active compounds of O. indicum was assessed via Traditional Chinese Medicine Systems Pharmacology Database (TCMSP), and the potential drug targets of O. indicum were identified using PharmMapper database. Additionally, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed via WebGestalt. Drug-target-pathway networks were constructed using Cytoscape to give a visual view. Our findings revealed that O. indicum has extremely superb druggability with 41 putative identified target genes. GO, KEGG, and network analyses showed that these targets were associated with inflammatory immunoreactions, cancer, and other biological processes. In summary, O. indicum is predicted to target multiple genes/proteins and pathways that shape a network which can exert systematic pharmacological effects.


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