scholarly journals Network Pharmacology Study on Molecular Mechanisms of Zhishi Xiebai Guizhi Decoction in the Treatment of Coronary Heart Disease

2021 ◽  
Vol 2021 ◽  
pp. 1-10
Author(s):  
Jin Gao ◽  
Yujing Pan ◽  
Yuxi Zhao ◽  
Haoyang Li ◽  
Zishuo Mi ◽  
...  
Keyword(s):  
Coronary Heart Disease ◽  
Clinical Trials ◽  
Heart Disease ◽  
Signaling Pathway ◽  
Molecular Mechanisms ◽  
Akt Signaling ◽  
Network Pharmacology ◽  
Akt Signaling Pathway ◽  
Ampk Signaling ◽  
Guizhi Decoction

Background. Coronary heart disease is characterized by the formation of arterial plaque. If not taken seriously, it will cause serious consequences such as myocardial infarction and heart failure. Zhishi Xiebai Guizhi Decoction first appeared in “Synopsis of Prescriptions of the Golden Chamber” and is a representative prescription for the treatment of coronary heart disease. This study aims to explain the mechanism of Zhishi Xiebai Guizhi Decoction in the treatment of coronary heart disease through network pharmacology and clinical trials. Methods. We first identified the core compounds of Zhishi Xiebai Guizhi Decoction and their potential targets through TCMSP. Then, We analyzed the molecular targets of Zhishi Xiebai Guizhi Decoction in coronary heart disease with OMIM and GeneCards databases. After the common targets were screened out, we manage to figure out the pathways of these target genes through STRING. Finally, we verify the treatment results in clinical trials. Results. Through network pharmacology analysis, we discovered that several core compounds of Zhishi Xiebai Guizhi Decoction have anti-inflammatory effects and are of great significance to treatment of cardiovascular diseases. The mechanism may be closely related to PPARγ, inflammation, TNF signaling pathway, AMPK signaling pathway, and PI3K-Akt signaling pathway. Clinical trials have also proved the key role of inflammation. Conclusions. Zhishi Xiebai Guizhi Decoction may play a role in treating coronary heart disease by activating PPARγ. TNF signaling pathway, AMPK signaling pathway, and PI3K-Akt signaling pathway are potential mechanisms as well. The application of network pharmacology can provide a novel method for the research of Chinese herbal medicine. We hope that Zhishi Xiebai Guizhi Decoction will be recognized as a complementary or alternative treatment for coronary heart disease.

Biological role of AKT, and regulation of AKT signaling pathway by thymoquinone: perspectives in cancer therapeutics

2020 ◽  
Vol 20 ◽  
Author(s):  
Md. Junaid ◽  
Yeasmin Akter ◽  
Syeda Samira Afrose ◽  
Mousumi Tania ◽  
Md. Asaduzzaman Khan
Keyword(s):  
Clinical Trials ◽  
Signaling Pathways ◽  
Signaling Pathway ◽  
Inhibitory Effect ◽  
Akt Signaling ◽  
Review Article ◽  
Therapeutic Drug ◽  
Akt Signaling Pathway ◽  
Anti Cancer

Background: AKT/PKB is an important enzyme with numerous biological functions, and its overexpression is related to the carcinogenesis. AKT stimulates different signaling pathways that are downstream of activated tyrosine kinases and phosphatidylinositol 3-kinase, hence functions as an important target for anti-cancer drugs. Objective: In this review article, we have interpreted the role of AKT signaling pathways in cancer and natural inhibitory effect of Thymoquinone (TQ) in AKT and its possible mechanism. Method: We have collected the updated information and data on AKT, their role in cancer and inhibitory effect of TQ in AKT signaling pathway from google scholar, PubMed, Web of Science, Elsevier, Scopus and many more. Results: There are many drugs already developed, which can target AKT, but very few among them have passed clinical trials. TQ is a natural compound, mainly found in black cumin, which has been found to have potential anti-cancer activities. TQ targets numerous signaling pathways, including AKT, in different cancers. In fact, many studies revealed that AKT is one of the major targets of TQ. The preclinical success of TQ suggests its clinical studies on cancer. Conclusion: This review article summarizes the role of AKT in carcinogenesis, its potent inhibitors in clinical trials, and how TQ acts as an inhibitor of AKT and TQ’s future as a cancer therapeutic drug.

scholarly journals A Network Pharmacology Analysis to Reveal the Molecular Mechanism of Zhizi-Danshen on Coronary Heart Disease

2020 ◽  
Author(s):  
Yue-hong Shen ◽  
Shu-lin Wang ◽  
Na Wu ◽  
Yu-chen Dai ◽  
Qian Zhou ◽  
...  
Keyword(s):  
Coronary Heart Disease ◽  
Heart Disease ◽  
Endothelial Function ◽  
Signaling Pathway ◽  
Target Genes ◽  
Cardiac Fibrosis ◽  
Fluid Shear Stress ◽  
Network Pharmacology ◽  
Vascular Endothelial ◽  
Vascular Endothelial Function

Abstract ObjectiveOur study aimed to investigate the potential mechanisms of the herb pair Zhizi-Danshen (ZD) for coronary heart disease (CHD) using network pharmacological data mining technology.MethodsThe Traditional Chinese Medicine System Pharmacology (TCMSP) database was used to collect the active ingredients of ZD and predict ZD-related target proteins. Afterwards, we identified CHD-related targets from DisGeNET database, NCBI gene database, and TTD database. The common targets both from ZD and CHD were screened by Venny2.1, which were then imported into the String database for protein-protein interaction (PPI) analysis. Finally, the GO and KEGG enrichment analysis were performed by R software, and the network construction was established using Cytoscape3.7.2.ResultsWe obtained 199 possible targets from 62 candidate ingredients of ZD and 1033 CHD-ralated targets, with 83 overlapping common target genes. Then, 11 core targets were acquired from PPI network analysis. Further, GO analysis showed that these common targets mainly influenced receptor ligand activity，cytokine activity，cytokine receptor binding，steroid hormone receptor activity, and peptide binding. KEGG pathway analysis indicated that ZD affected CHD through seven important pathways linked to vascular endothelial function regulation (fluid shear stress and atherosclerosis，AGE-RAGE signaling pathway in diabetic complications, HIF-1 signaling pathway), imflammatory effects (IL-17 signaling pathway, TNF signaling pathway，Toll-like receptor signaling pathway)，and hormone regulation (relaxin signaling pathway). ConclusionsThis study revealed the potential pharmacological mechanisms of ZD against CHD, which were mainly associated with regulation of vascular endothelial function and inflammatory effects, promotion of vasodilatation, and prevention of cardiac fibrosis. Moreover, it provided a novel conception for the development of alternative therapies on CHD.

scholarly journals Investigating the Pharmacological Mechanisms of SheXiang XinTongNing Against Coronary Heart Disease Based on Network Pharmacology and Experimental Evaluation

2021 ◽  
Vol 12 ◽  
Author(s):  
Li-ying Jia ◽  
Gui-yun Cao ◽  
Jia Li ◽  
Lu Gan ◽  
Jin-xin Li ◽  
...  
Keyword(s):  
Coronary Heart Disease ◽  
Heart Disease ◽  
Signaling Pathway ◽  
Cell Apoptosis ◽  
Experimental Evaluation ◽  
Mapk Signaling ◽  
Chinese Herbs ◽  
Network Pharmacology ◽  
Tunel Staining

SheXiang XinTongNing (XTN), which is composed of six traditional Chinese herbs, is a commercially available Chinese patent medicine that has been widely used as the treatment of coronary heart disease (CHD). Its mechanisms against coronary heart disease, however, remain largely unknown. This study aimed to investigate the pharmacological mechanisms of XTN against CHD via network pharmacology and experimental evaluation. In this study, GO enrichment and KEGG pathway enrichment were firstly performed for acquiring the potentially active constituents of XTN, the candidate targets related to coronary heart disease, the drug-components-targets network as well as the protein-protein interaction network and further predicting the mechanisms of XTN against coronary heart disease. Subsequently, a series of in vitro experiments, specifically MTT assay, flow cytometry and Real-time quantitative polymerase chain reaction analysis, and a succession of in vivo experiments, including Tunel staining and immunohistochemical staining were conducted for further verification. Results showed that Bcl-2, IGF1, CASP3 were the key candidate targets which significantly associated with multiple pathways, namely PI3K-Akt signaling pathway and MAPK signaling pathway. It indicated that the potential mechanism of XTN against CHD may be predominantly associated with cell apoptosis. The in vitro experimental results showed that XTN treatment remarkably decreased the apoptotic rate and Bax/Bcl-2 ratio of H9c2 cells. Histological results confirmed that XTN not only effectively alleviated oxidative damage caused by myocardial ischemia but inhibited cell apoptosis. Given the above, through the combined utilization of virtual screening and experimental verification, the findings suggest that XTN makes a significant contribution in protecting the heart from oxidative stress via regulating apoptosis pathways, which lays the foundations and offers an innovative idea for future research.

scholarly journals TIPE Regulates DcR3 Expression and Function by Activating the PI3K/AKT Signaling Pathway in CRC

2021 ◽  
Vol 10 ◽  
Author(s):  
Mengya Zhong ◽  
Xingfeng Qiu ◽  
Yu Liu ◽  
Yan Yang ◽  
Lei Gu ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Signaling Pathway ◽  
Molecular Mechanisms ◽  
Akt Signaling ◽  
Luciferase Reporter ◽  
Akt Signaling Pathway ◽  
Cell Proliferation And Migration ◽  
And Migration ◽  
Hct116 Cells ◽  
Proliferation And Migration

Tumor necrosis factor-induced protein-8 (TIPE) is highly expressed in colorectal cancer (CRC). Decoy receptor 3 (DcR3) is a soluble secreted protein that can antagonize Fas ligand (FasL)-induced apoptosis and promote tumorigenesis. It remains unclear whether TIPE can regulate DcR3 expression. In this study, we examined this question by analyzing the relationship between these factors in CRC. Bioinformatics and tissue microarrays were used to determine the expression of TIPE and DcR3 and their correlation in CRC. The expression of TIPE and DcR3 in colon cancer cells was detected. Plasma samples were collected from CRC patients, and DcR3 secretion was measured. Then, dual-luciferase reporter gene analysis was performed to assess the interaction between TIPE and DcR3. We exogenously altered TIPE expression and analyzed its function and influence on DcR3 secretion. Lipopolysaccharide (LPS) was used to stimulate TIPE-overexpressing HCT116 cells, and alterations in signaling pathways were detected. Additionally, inhibitors were used to confirm molecular mechanisms. We found that TIPE and DcR3 were highly expressed in CRC patients and that their expression levels were positively correlated. DcR3 was highly expressed in the plasma of cancer patients. We confirmed that TIPE and DcR3 were highly expressed in HCT116 cells. TIPE overexpression enhanced the transcriptional activity of the DcR3 promoter. TIPE activated the PI3K/AKT signaling pathway to regulate the expression of DcR3, thereby promoting cell proliferation and migration and inhibiting apoptosis. In summary, TIPE and DcR3 are highly expressed in CRC, and both proteins are associated with poor prognosis. TIPE regulates DcR3 expression by activating the PI3K/AKT signaling pathway in CRC, thus promoting cell proliferation and migration and inhibiting apoptosis. These findings may have clinical significance and promise for applications in the treatment or prognostication of CRC.

scholarly journals Study on the Effective Material Basis and Mechanism of Traditional Chinese Medicine Prescription (QJC) Against Stress Diarrhea in Mice

2021 ◽  
Vol 8 ◽  
Author(s):  
Yuefeng Zhang ◽  
Fei Yu ◽  
Jingyou Hao ◽  
Eliphaz Nsabimana ◽  
Yanru Wei ◽  
...  
Keyword(s):  
Chinese Medicine ◽  
Traditional Chinese Medicine ◽  
Signaling Pathway ◽  
Pathological Condition ◽  
Akt Signaling ◽  
Network Pharmacology ◽  
Akt Signaling Pathway ◽  
Expression Levels ◽  
Medicine Prescription ◽  
Chinese Medicine Prescription

Stress diarrhea is a major challenge for weaned piglets and restricts pig production efficiency and incurs massive economic losses. A traditional Chinese medicine prescription (QJC) composed of Astragalus propinquus Schischkin (HQ), Zingiber officinale Roscoe (SJ), and Plantago asiatica L. (CQC) has been developed by our laboratory and shows marked anti-stress diarrhea effect. However, the active compounds, potential targets, and mechanism of this effect remain unclear and warrant further investigation. In our study, we verified the bioactive compounds of QJC and relevant mechanisms underlying the anti-stress diarrhea effect through network pharmacology and in vivo experimental studies. After establishing a successful stress-induced diarrhea model, histomorphology of intestinal mucosa was studied, and Quantitative real-time PCR (RT-qPCR) probe was used for the phosphoinositide 3-kinase (PI3K)–Akt signaling pathway to verify the therapeutic effect of QJC on diarrhea. First, using the network pharmacology approach, we identified 35 active components and 130 Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways in QJC. From among these, we speculated that quercetin, luteolin, kaempferol, scutellarein, and stigmasterol were the main bioactive compounds and assumed that the anti-diarrhea effect of QJC was related to the PI3K–Akt signaling pathway. The RT-qPCR indicated that QJC and its bioactive components increased the expression levels of PI3K and Akt, inhibited the expression of phosphatase and tensin homolog (PTEN), and activated the PI3K–Akt signaling pathway to relieve stress-induced diarrhea. Furthermore, we found that QJC alleviated the pathological condition of small intestine tissue and improved the integrity of the intestinal barrier. Taken together, our study showed that the traditional Chinese medicine QJC, quercetin, luteolin, kaempferol, scutellarein, and stigmasterol alleviated the pathological condition of small intestine tissue and relieved stress-induced diarrhea by increasing the expression levels of PI3K and Akt and inhibiting the expression levels of PTEN.

scholarly journals A Network Pharmacology-Based Study on Active Ingredients of Corydalis Rhizoma on Coronary Heart Disease

2020 ◽  
Author(s):  
Ying Li ◽  
Guhang Wei ◽  
Zhenkun Zhuang ◽  
Mingtai Chen ◽  
Changjian Yuan ◽  
...  
Keyword(s):  
Coronary Heart Disease ◽  
Heart Disease ◽  
Chinese Medicine ◽  
Traditional Chinese Medicine ◽  
Rna Polymerase ◽  
Rna Polymerase Ii ◽  
Signaling Pathway ◽  
Network Pharmacology ◽  
Active Ingredients ◽  
Active Components

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.

scholarly journals Compound K Inhibits Autophagy-Mediated Apoptosis Through Activation of the PI3K-Akt Signaling Pathway Thus Protecting Against Ischemia/Reperfusion Injury

2018 ◽  
Vol 47 (6) ◽  
pp. 2589-2601 ◽  
Author(s):  
Xiangyan Li ◽  
Qingxia Huang ◽  
Manying Wang ◽  
Xiuci Yan ◽  
Xinying Song ◽  
...  
Keyword(s):  
Cell Viability ◽  
Signaling Pathway ◽  
Molecular Mechanisms ◽  
Ischemia Reperfusion ◽  
Akt Signaling ◽  
Mitochondrial Damage ◽  
Tunel Staining ◽  
Ros Generation ◽  
Akt Signaling Pathway ◽  
Compound K

Background/Aims: A series of reports revealed that autophagy and apoptosis exerted detrimental effects on the pathology of cardiac ischemia/reperfusion (I/R) injury. Ginsenoside compound K (CK), a major intestinal metabolite underlying the pharmacological actions of orally administered ginseng, has a protective effect against myocardial I/R injury. However, the molecular mechanisms by which CK protects against I/R injury remain unclear. In this study, we hypothesized that the cardioprotective effects of CK against I/R injury are mediated by inhibiting autophagy/apoptosis-related signaling pathways in H9c2 cardiomyocyte cells. Methods: H9c2 cells were incubated with CK and exposed to I/R. Cell viability and damage was analyzed by MTT and lactate dehydrogenase assays. Reactive oxygen species (ROS) generation, mitochondrial damage, and cell apoptosis were analyzed by flow cytometry and TUNEL staining. The expression of autophagy, apoptosis, and related signaling proteins was analyzed by Western blotting and immunofluorescence staining. Results: CK pretreatment promoted cell viability and attenuated ROS accumulation and intracellular mitochondrial damage induced by I/R injury Moreover, CK reduced autophagy by regulating the formation of phagocytic precursors to autophagosomes and also inhibited apoptosis through a mitochondrial-mediated pathway. Additionally the cardioprotective effect of CK against I/R injury was mainly through the activation of the PI3K-Akt signaling pathway. Conclusions: CK pretreatment inhibits autophagy-mediated apoptosis induced by I/R injury through the activation of the PI3K-Akt signaling pathway, which reveals that CK may be one of the key bioactive ingredients of ginseng for the treatment of myocardial I/R injury.

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