scholarly journals The modulatory properties of Astragalus membranaceus treatment on endometrial cancer: an integrated pharmacological method

PeerJ ◽  
2021 ◽  
Vol 9 ◽  
pp. e11995
Author(s):  
Qianqian Zhang ◽  
Xianghua Huang

Astragalus membranaceus is a traditional Chinese medicine and has been used for adjuvant clinical therapy for a variety of cancers. However, the mechanism of its action on endometrial carcinoma is unclear. Based on the Gene Expression Omnibus (GEO) database, the Cancer Genome Atlas (TCGA) database, and the Traditional Chinese Medicine System Pharmacology Database (TCMSP™), the drug and target compounds were initially screened to construct a common network module. Twenty active compounds in Astragalus membranaceus were successfully identified, which hit by 463 potential targets related to endometrial cancer. Eight of the more highly predictive compounds (such as Jaranol, Bifendate, Isorhamnetin, Calycosin, 7-O-methylisomucronulatol, Formononetin, Kaempferol, Quercetin) were involved in DNA integrity checkpoint, cyclin-dependent protein kinase holoenzyme complex, and histone kinase activity. Additionally, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway confirmed that Astragalus membranaceus might play a role in the treatment of endometrial cancer through p53 signalling pathway, transcriptional misregulation in cancer, and endometrial cancer signalling pathway. Drug-target-pathway networks were constructed using Cytoscape to provide a visual perspective. In addition, we verified that formononetin inhibited the proliferation of endometrial cancer cells through cell viability tests and clone formation tests. And qPCR and western blot found that formononetin exerts anti-cancer effects by promoting the expression of estrogen receptor beta (ERβ) and p53. Based on a systematic network pharmacology approach, our works successfully predict the active ingredients and potential targets of Astragalus membranaceus for application to endometrial cancer and helps to illustrate mechanism of action on a comprehensive level.

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. 1-13 ◽  
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.


2021 ◽  
Vol 12 ◽  
Author(s):  
Ning-Juan Yang ◽  
Yan-Ru Liu ◽  
Zhi-Shu Tang ◽  
Jin-Ao Duan ◽  
Ya-Feng Yan ◽  
...  

The traditional Chinese medicine Poria cum Radix Pini (PRP) is a fungal medicinal material that has been proven to play an important role in the treatment of arrhythmia. However, the mechanism of its effect on arrhythmia is still unclear. In this study, network pharmacology and metabolomics correlation analysis methods were used to determine the key targets, metabolites and potential pathways involved in the effects of PRP on arrhythmia. The results showed that PRP can significantly improve cardiac congestion, shorten the SV-BA interval and reduce the apoptosis of myocardial cells induced by barium chloride in zebrafish. By upregulating the expression of the ADORA1 protein and the levels of adenosine and cGMP metabolites in the cGMP-PKG signalling pathway, PRP can participate in ameliorating arrhythmia. Therefore, we believe that PRP shows great potential for the treatment of arrhythmia.


2021 ◽  
Vol 2021 ◽  
pp. 1-13
Author(s):  
Shuhan Zhou ◽  
Yanjun Duan ◽  
Yu Deng ◽  
Miao Wang ◽  
Chaoqun Huang ◽  
...  

Chronic gastritis (CG) places a considerable burden on the healthcare system worldwide. Traditional Chinese Medicine (TCM) formulas characterized by multicompounds and multitargets have been acknowledged with striking effects in the treatment of CG in China’s history. Nevertheless, their accurate mechanisms of action are still ambiguous. In this study, we analyzed the effective compounds, potential targets, and related biological pathway of Lianpu Drink (LPD), a TCM formula which has been reported to have a therapeutic effect on CG, by contrasting a “compound-target-disease” network. According to the results, 92 compounds and 5762 putative targets of LPD were screened; among them, 8 compounds derived from different herbs in LPD and 30 common targets related to LPD and CG were selected as candidate compounds and precision targets, respectively. Meanwhile, the predicted common targets were verified by Kyoto Encyclopedia of Genes and Genomes (KEGG) signaling pathway analysis and pharmacological experiments. The results demonstrated that quercetin, ephedrine, trigonelline, crocetin, and β-sitosterol were major effective compounds of LPD responsible for the CG treatment by inhibiting the activation of the JAK 2-STAT 3 signaling pathway to reduce the expressions of cyclin D1 and Bcl-2 proteins. The study provides evidence for the mechanism of understanding of LPD for the treatment of CG.


2020 ◽  
Vol 2020 ◽  
pp. 1-15
Author(s):  
Wenchao Dan ◽  
Jinlei Liu ◽  
Xinyuan Guo ◽  
Boran Zhang ◽  
Yi Qu ◽  
...  

Background and Aim. Antineoplastic drug-induced cardiotoxicity (ADIC) becomes the second leading cause of death for tumor survivors after tumor recurrence and metastasis, and there may be great room for development in the future of traditional Chinese medicine (TCM). However, the theory of anticardiotoxicity of TCM has not yet formed a system. This study aimed to explore the material basis and the rule of TCM against ADIC based on network pharmacology and data mining. Methods. The targets of antineoplastic drugs with cardiotoxicity were obtained from the National Center for Biotechnology Information (NCBI) database, China national knowledge infrastructure (CNKI) database, and Swiss Target Prediction platform. Then, the cardiotoxicity-related targets were derived from the Gene Cards, Disgenet, OMIM, and DrugBank databases, as well as the drug of current clinical guidelines. The targets both in these two sets were regarded as potential targets to alleviate ADIC. Then, candidate compounds and herbs were matched via Traditional Chinese Medicine Systems Pharmacology (TCMSP) platform. Cytoscape3.7.1 was used to set up the target-compound-herb network. Molecular docking between core targets and compounds was performed with AutodockVina1.1.2. The rules of herbs were summarized by analyzing their property, flavor, and channel tropism. Results. Twenty-one potential targets, 332 candidate compounds, and 400 kinds of herbs were obtained. Five core targets including potassium voltage-gated channel subfamily H member 2 (KCNH2), cyclin-dependent kinase 1 (CDK1), matrix metalloproteinase 2 (MMP2), mitogen-activated protein kinase1 (MAPK1), and tumor protein p53 (TP53) and 29 core compounds (beta-sitosterol, quercetin, kaempferol, etc.) were collected. Five core herbs (Yanhusuo, Gouteng, Huangbai, Lianqiao, and Gancao) were identified. Also, the TCM against ADIC were mainly bitter and acrid in taste, warm in property, and distributed to the liver and lung meridians. Conclusion. TCM against ADIC has great potential. Our study provides a new method and ideas for clinical applications of integrated Chinese and western medicine in treating ADIC.


2020 ◽  
Vol 2020 ◽  
pp. 1-23
Author(s):  
Liping Sun ◽  
Dandan Wang ◽  
Yan Xu ◽  
Wenxiu Qi ◽  
Yanbo Wang

Pneumonia is a serious global health problem and the leading cause of mortality in children. Antibiotics are the main treatment for bacterial pneumonia, but there are serious drug resistance problems. Traditional Chinese medicine (TCM) has been used to treat diseases for thousands of years and has a unique theory. This article takes the treatment of pneumonia with Ephedra sinica as a representative hot medicine and Scutellariae Radix as a representative cold medicine as an example. We explore and explain the theory of treating the same disease with different TCM treatments. Using transcriptomics and network pharmacology methods, GO, KEGG enrichment, and PPI network construction were carried out, demonstrating that Ephedra sinica plays a therapeutic role through the NF-κB and apoptosis signaling pathways targeting PLAU, CD40LG, BLC2L1, CASP7, and CXCL8. The targets of Scutellariae Radix through the IL-17 signaling pathway are MMP9, CXCL8, and MAPK14. Molecular docking technology was also used to verify the results. In short, our results provide evidence for the theory of treating the same disease with different treatments, and we also discuss future directions for traditional Chinese medicine.


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