scholarly journals Studies of the Anti-Diabetic Mechanism of Pueraria lobata Based on Metabolomics and Network Pharmacology

Processes ◽  
2021 ◽  
Vol 9 (7) ◽  
pp. 1245
Author(s):  
Shu Zhang ◽  
Qi Ge ◽  
Liang Chen ◽  
Keping Chen
Keyword(s):  
Signaling Pathway ◽  
Diabetes Complications ◽  
Mapk Signaling ◽  
Network Pharmacology ◽  
Pueraria Lobata ◽  
Insulin Deficiency ◽  
Active Ingredients ◽  
Foxo Signaling Pathway ◽  
Anti Inflammation

Diabetes mellitus (DM), as a chronic disease caused by insulin deficiency or using obstacles, is gradually becoming a principal worldwide health problem. Pueraria lobata is one of the traditional Chinese medicinal and edible plants, playing roles in improving the cardiovascular system, lowering blood sugar, anti-inflammation, anti-oxidation, and so on. Studies on the hypoglycemic effects of Pueraria lobata were also frequently reported. To determine the active ingredients and related targets of Pueraria lobata for DM, 256 metabolites were identified by LC/MS non targeted metabonomics, and 19 active ingredients interacting with 51 DM-related targets were screened. The results showed that puerarin, quercetin, genistein, daidzein, and other active ingredients in Pueraria lobata could participate in the AGE-RAGE signaling pathway, insulin resistance, HIF-1 signaling pathway, FoxO signaling pathway, and MAPK signaling pathway by acting on VEGFA, INS, INSR, IL-6, TNF and AKT1, and may regulate type 2 diabetes, inflammation, atherosis and diabetes complications, such as diabetic retinopathy, diabetic nephropathy, and diabetic cardiomyopathy.

scholarly journals Use of Network Pharmacology to Explore the Mechanism of Gegen (Puerariae lobatae Radix) in the Treatment of Type 2 Diabetes Mellitus Associated with Hyperlipidemia

2021 ◽  
Vol 2021 ◽  
pp. 1-14
Author(s):  
Guozhen Yuan ◽  
Shuai Shi ◽  
Qiulei Jia ◽  
Jingjing Shi ◽  
Shuqing Shi ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Signaling Pathway ◽  
Fluid Shear Stress ◽  
Chinese Herbs ◽  
Network Pharmacology ◽  
Biological Processes ◽  
Active Ingredients

Rapid increases in metabolic disorders, such as type 2 diabetes mellitus (T2DM) and hyperlipidemia, are becoming a substantial challenge to worldwide public health. Traditional Chinese medicine has a long history and abundant experience in the treatment of diabetes and hyperlipidemia, and Puerariae lobatae Radix (known as Gegen in Chinese) is one of the most prevalent Chinese herbs applied to treat these diseases. The underlying mechanism by which Gegen simultaneously treats diabetes and hyperlipidemia, however, has not been clearly elucidated to date. Therefore, we systematically explored the potential mechanism of Gegen in the treatment of T2DM complicated with hyperlipidemia based on network pharmacology. We screened the potential targets of Gegen, T2DM, and hyperlipidemia in several online databases. Then, the hub targets were analyzed by performing protein-protein interaction, Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment assays, and finally, the complicated connections among compounds, targets, and pathways were visualized in Cytoscape. We found that isoflavones, including daidzein, genistein, and puerarin, as well as β-sitosterol, are the key active ingredients of Gegen responsible for its antidiabetic and antihyperlipidemia effects, which mainly target AKR1B1, EGFR, ESR, TNF, NOS3, MAPK3, PPAR, CYP19A1, INS, IL6, and SORD and multiple pathways, such as the PI3K-Akt signaling pathway; the AGE-RAGE signaling pathway in diabetic complications, fluid shear stress, and atherosclerosis; the PPAR signaling pathway; insulin resistance; the HIF-1 signaling pathway; the TNF signaling pathway; and others. These active ingredients also target multiple biological processes, including the regulation of glucose and lipid metabolism, the maintenance of metabolic homeostasis, and anti-inflammatory and antioxidant pathways. In conclusion, Gegen is a promising therapeutic phytomedicine for T2DM with hyperlipidemia that targets multiple proteins, biological processes, and pathways.

scholarly journals Therapeutic mechanism of Toujie Quwen granules in COVID-19 based on network pharmacology

2020 ◽  
Vol 13 (1) ◽  
Author(s):  
Ying Huang ◽  
Wen-jiang Zheng ◽  
Yong-shi Ni ◽  
Mian-sha Li ◽  
Jian-kun Chen ◽  
...  
Keyword(s):  
Chinese Medicine ◽  
Signaling Pathways ◽  
Signaling Pathway ◽  
Mapk Signaling ◽  
Venn Diagram ◽  
Network Pharmacology ◽  
Active Ingredients ◽  
Integrated Network ◽  
Therapeutic Mechanism ◽  
The World

Abstract Background Chinese medicine Toujie Quwen granule (TJQW) has proven to be effective in the treatment of mild coronavirus disease 2019 (COVID-19) cases by relieving symptoms, slowing the progression of the disease, and boosting the recovery of patients. But the bioactive compounds and potential mechanisms of TJQW for COVID-19 prevention and treatment are unclear. This study aimed to explore the potential therapeutic mechanism of TJQW in coronavirus disease 2019 (COVID-19) based on an integrated network pharmacology approach. Methods TCMSP were used to search and screen the active ingredients in TJQW. The Swiss TargetPrediction was used to predict the potential targets of active ingredients. Genes co-expressed with ACE2 were considered potential therapeutic targets on COVID-19. Venn diagram was created to show correlative targets of TJQW against COVID-19. Cytoscape was used to construct a “drug-active ingredient-potential target” network, STRING were used to construct protein-protein interaction network, and cytoHubba performed network topology analysis. Enrichment of biological functions and signaling pathways of core targets was performed by using the clusterProfiler package in R software and ClueGO with CluePedia plugins in Cytoscape. Results A total of 156 active ingredients were obtained through oral bioavailability and drug-likeness screenings. Two hundred twenty-seven potential targets of TJQW were related to COVID-19. The top ten core targets are EGFR, CASP3, STAT3, ESR1, FPR2, F2, BCL2L1, BDKRB2, MPO, and ACE. Based on that, we obtained 19 key active ingredients: umbelliprenin, quercetin, kaempferol, luteolin, praeruptorin E, stigmasterol, and oroxylin A. And the enrichment analysis obtained multiple related gene ontology functions and signaling pathways. Lastly, we constructed a key network of “drug-component-target-biological process-signaling pathway”. Our findings suggested that TJQW treatment for COVID-19 was associated with elevation of immunity and suppression of inflammatory stress, including regulation of inflammatory response, viral process, neutrophil mediated immunity, PI3K-Akt signaling pathway, MAPK signaling pathway, Jak-STAT signaling pathway, Complement and coagulation cascades, and HIF-1 signaling pathway. Conclusions Our study uncovered the pharmacological mechanism underlying TJQW treatment for COVID-19. These results should benefit efforts for people around the world to gain more knowledge about Chinese medicine TJQW in the treatment of this vicious epidemic COVID-19, and help to address this pressing problem currently facing the world.

scholarly journals Research on the Mechanism of Wuwei Yuganzi San in the Treatment of Coronary Heart Disease Based on Network Pharmacology

2021 ◽  
Author(s):  
Qunhui Zhang ◽  
Yimei Li ◽  
Yang Guo ◽  
Qiqin Lu ◽  
Guoying Zhang ◽  
...  
Keyword(s):  
Coronary Heart Disease ◽  
Heart Disease ◽  
Signaling Pathway ◽  
Protein Interaction ◽  
Mapk Signaling ◽  
Receptor Protein ◽  
Network Pharmacology ◽  
Ras Signaling ◽  
Ppi Network ◽  
Active Ingredients

Abstract Background: Coronary heart disease (CHD) is a chronic cardiovascular disease across the world, which poses numerous threats to mankind. Wuwei Yuganzi San (WYS) is a famous traditional Tibetan medicine prescription. It has been confirmed effective in the treatment of CHD, but its specific mechanism remains still unclear. Objective: To elucidate the main pharmacological action of WYS in treating CHD and investigate the underlying multiple mechanisms of its multi-ingredient-multi-target by network pharmacology.Methods: Firstly, active ingredients of WYS and connected targets of five herbs were retrieved by using traditional Chinese medicine systems pharmacology (TCMSP) and screening literature. Then, genome explanation databases (OMIM and GeneCards) were used to acquire targets related to CHD. The protein-protein interaction (PPI) network was built using the mutual targets filtering genes through protein interaction. Next, a network diagram could be established with the help of Cytoscape 3.8.2. And, STRING platform was used to construct a protein interaction network. Finally, GO and KEGG analyses were analyzed to further elucidate biological process enrichment.Results: After the screening, 36 active ingredients and 202 related targets in WYS in addition to 952 disease-related targets were acquired. A total of 37 key targets including AKT1, ESR1, and EGFR were screened in the PPI network. These targets were mostly concentrated on the transmembrane receptor protein tyrosine kinase signaling pathway, cellular response to growth factors stimulus, and response to growth factor. The KEGG enrichment demonstrated that the MAPK signaling pathway, P13K/AKT signaling pathway, Ras signaling pathway, and other corresponding signaling pathways were closely related to CHD.Conclusions. WYS plays a significant role in the treatment of CHD. And this study provides a novel approach to disclose the therapeutic mechanisms of WYS on CHD.

scholarly journals Study of Components and Mechanism of Juechuang Against Platelet Aggregation Based on Network Pharmacology

2020 ◽  
Vol 15 (9) ◽  
pp. 1934578X2094129
Author(s):  
Zhou-Tao Xie ◽  
Bo Liu ◽  
Yi-yi Xiong ◽  
Yan-Fang Yang ◽  
He-Zhen Wu
Keyword(s):  
Molecular Docking ◽  
Platelet Aggregation ◽  
Signaling Pathway ◽  
Mapk Signaling ◽  
Network Pharmacology ◽  
Pathway Enrichment Analysis ◽  
Ras Signaling ◽  
Active Ingredients ◽  
Aggregation Mechanism ◽  
Antiplatelet Aggregation

Juechuang, a traditional Chinese herbal medicine, is originated from Rostellularia procumbens (L.) Nees. Many studies have shown that the ethyl acetate extract from Juechaung may inhibit platelet aggregation. However, the antiplatelet aggregation mechanism of Juechuang requires more systematic research. In this article, network pharmacology was used to explore the antiplatelet aggregation components and its antiplatelet aggregation mechanism. Different components were evaluated and screened by pharmacokinetic characteristics. The potential targets of active ingredients were predicted by a reverse pharmacophore matching method, and the targets were screened according to targets related to antiplatelet aggregation in the GeneCards database. Thus, an interaction network of component-target-pathway of Juechuang was generated using Cytoscape 3.2.1. software. Furthermore, the binding energy of relevant active components with key targets was calculated using a Lamarck genetic algorithm in the molecular docking calculations. Finally, the study identified 28 potentially active ingredients in Juechuang, providing further evidence that the active ingredients act on 277 targets, and 38 protein targets related to antiplatelet aggregation were screened. Through the Kyoto encyclopedia of genes and genome pathway enrichment analysis, we found that the mechanism of antiplatelet aggregation may be related to the Ras signaling pathway, platelet activation signaling pathway, mitogen-activated protein kinase (MAPK) signaling pathway, etc. Via molecular docking of 2 targets, non-receptor tyrosine kinases(SRC) and MAPK were selected for molecular docking. By comparing the molecular docking results of Chinensinaphthol, Taiwanin E, Tuberculatin, Cycloeucalenol, and Justicidin B to the control drug, we found that those test molecules combined with targets and lead to high binding activity. These molecular docking results were also consistent with the literature values, and they helped identify the active ingredients and assured the reliability of the network analysis. This study may further provide a reference for the systematic study of the pharmacodynamic effect and the antiplatelet aggregation mechanism of Juechuang.

scholarly journals To Explore the Mechanism and Equivalent Molecular Group of Fuxin Mixture in Treating Heart Failure Based on Network Pharmacology

2020 ◽  
Vol 2020 ◽  
pp. 1-10
Author(s):  
Yi-ding Yu ◽  
Yi-ping Xiu ◽  
Yang-fan Li ◽  
Yi-tao Xue
Keyword(s):  
Heart Failure ◽  
Signaling Pathway ◽  
Enrichment Analysis ◽  
Mapk Signaling ◽  
New Drugs ◽  
Network Pharmacology ◽  
Active Ingredients ◽  
Nf Kappa B ◽  
Vegf Signaling ◽  
Molecular Group

Fuxin mixture (FXHJ) is a prescription for the treatment of heart failure. It has been shown to be effective in clinical trials, but its active ingredients and mechanism of action are not completely clear, which limits its clinical application and international promotion. In this study, we used network pharmacology to find, conclude, and summarize the mechanism of FXHJ in the treatment of heart failure. From FXHJ, we found 39 active ingredients and 47 action targets. Next, we constructed the action network and was conducted enrichment analysis. The results showed that FXHJ mainly treated heart failure by regulating the MAPK signaling pathway, PI3KAkt signaling pathway, cAMP signaling pathway, TNF signaling pathway, toll-like receptor signaling pathway, VEGF signaling pathway, NF-kappa B signaling pathway, and the apoptotic signaling molecule BCL2. Through the research method of network pharmacology, this study summarized the preliminary experiments of the research group and revealed the probable mechanism of FXHJ in the treatment of heart failure to a certain extent, which provided some ideas for the development of new drugs.

scholarly journals Exploring the Mechanism of Total Flavonoids of Drynariae Rhizoma to Improve Large Bone Defects by Network Pharmacology and Experimental Assessment

2021 ◽  
Vol 12 ◽  
Author(s):  
Weipeng Sun ◽  
Minying Li ◽  
Lei Xie ◽  
Zhexing Mai ◽  
Yan Zhang ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Bone Defects ◽  
Mapk Signaling ◽  
Mapk Signaling Pathway ◽  
Network Pharmacology ◽  
Dosage Group ◽  
Active Ingredients ◽  
Large Bone ◽  
Large Bone Defects

Drynariae Rhizoma (DR) has been demonstrated to be effective in promoting fracture healing in clinical use. In the study, we tried to predicate potential signaling pathways and active ingredients of DR via network pharmacology, uncover its regulation mechanism to improve large bone defects by in vivo and in vitro experiment. We total discovered 18 potential active ingredients such as flavonoids and 81 corresponding targets, in which mitogen-activated protein kinase (MAPK) signaling pathway has the highest correlation with bone defects in pathway and functional enrichment analysis. Therefore, we hypothesized that flavonoids in DR improve large bone defects by activating MAPK signaling pathway. Animal experiments were carried out and all rats randomly divided into TFDR low, medium, and high dosage group, model group and control group. 12 weeks after treatment, according to X-ray and Micro-CT, TFDR medium dosage group significantly promote new bone mineralization compared with other groups. The results of HE and Masson staining and in vitro ALP level of BMSC also demonstrated the formation of bone matrix and mineralization in the TFDR groups. Also, angiographic imaging suggested that flavonoids in DR promoting angiogenesis in the defect area. Consistently, TFDR significantly enhanced the expression of BMP-2, RUNX-2, VEGF, HIF-1 in large bone defect rats based on ELISA and Real-Time PCR. Overall, we not only discover the active ingredients of DR in this study, but also explained how flavonoids in DR regulating MAPK signaling pathway to improve large bone defects.

scholarly journals Molecular mechanism underlying the hypolipidemic effect of Shanmei Capsule based on network pharmacology and molecular docking

2021 ◽  
Vol 29 ◽  
pp. 239-256
Author(s):  
Qian Wang ◽  
Lijing Du ◽  
Jiana Hong ◽  
Zhenlin Chen ◽  
Huijian Liu ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Signaling Pathway ◽  
Molecular Mechanism ◽  
Kegg Pathway ◽  
Network Pharmacology ◽  
Pathway Enrichment Analysis ◽  
Signal Pathways ◽  
Hypolipidemic Effect ◽  
Active Ingredients ◽  
Pathway Enrichment

BACKGROUND: Shanmei Capsule is a famous preparation in China. However, the related mechanism of Shanmei Capsule against hyperlipidemia has yet to be revealed. OBJECTIVE: To elucidate underlying mechanism of Shanmei Capsule against hyperlipidemia through network pharmacology approach and molecular docking. METHODS: Active ingredients, targets of Shanmei Capsule as well as targets for hyperlipidemia were screened based on database. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment were performed via Database for Annotation, Visualization, and Integrated Discovery (DAVID) 6.8 database. Ingredient-target-disease-pathway network was visualized utilizing Cytoscape software and molecular docking was performed by Autodock Vina. RESULTS: Seventeen active ingredients in Shanmei Capsule were screened out with a closely connection with 34 hyperlipidemia-related targets. GO analysis revealed 40 biological processes, 5 cellular components and 29 molecular functions. A total of 15 signal pathways were enriched by KEGG pathway enrichment analysis. The docking results indicated that the binding activities of key ingredients for PPAR-α are equivalent to that of the positive drug lifibrate. CONCLUSIONS: The possible molecular mechanism mainly involved PPAR signaling pathway, Bile secretion and TNF signaling pathway via acting on MAPK8, PPARγ, MMP9, PPARα, FABP4 and NOS2 targets.

scholarly journals Potential mechanisms of Guizhi decoction against hypertension based on network pharmacology and Dahl salt-sensitive rat model

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Jiye Chen ◽  
Yongjian Zhang ◽  
Yongcheng Wang ◽  
Ping Jiang ◽  
Guofeng Zhou ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Rat Model ◽  
Experimental Studies ◽  
Matrix Metalloproteinase 2 ◽  
Network Pharmacology ◽  
Pathway Enrichment Analysis ◽  
Therapeutic Effects ◽  
Active Ingredients ◽  
Active Compounds ◽  
Guizhi Decoction

Abstract Background Guizhi decoction (GZD), a classical Chinese herbal formula, has been widely used to treat hypertension, but its underlying mechanisms remain elusive. The present study aimed to explore the potential mechanisms and therapeutic effects of GZD on hypertension by integrating network pharmacology and experimental validation. Methods The active ingredients and corresponding targets were collected from the Traditional Chinese Medicine Systems Pharmacology database and Analysis Platform (TCMSP). The targets related to hypertension were identified from the CTD, GeneCards, OMIM and Drugbank databases. Multiple networks were constructed to identify the key compounds, hub targets, and main biological processes and pathways of GZD against hypertension. The Surflex-Dock software was used to validate the binding affinity between key targets and their corresponding active compounds. The Dahl salt-sensitive rat model was used to evaluate the therapeutic effects of GZD against hypertension. Results A total of 112 active ingredients, 222 targets of GZD and 341 hypertension-related targets were obtained. Furthermore, 56 overlapping targets were identified, five of which were determined as the hub targets for experimental verification, including interleukin 6 (IL-6), C–C motif chemokine 2 (CCL2), IL-1β, matrix metalloproteinase 2 (MMP-2), and MMP-9. Pathway enrichment analysis results indicated that 56 overlapping targets were mainly enriched in several inflammation pathways such as the tumor necrosis factor (TNF) signaling pathway, Toll-like receptor (TLR) signaling pathway and nuclear factor kappa-B (NF-κB) signaling pathway. Molecular docking confirmed that most active compounds of GZD could bind tightly to the key targets. Experimental studies revealed that the administration of GZD improved blood pressure, reduced the area of cardiac fibrosis, and inhibited the expression of IL-6, CCL2, IL-1β, MMP-2 and MMP-9 in rats. Conclusion The potential mechanisms and therapeutic effects of GZD on hypertension may be attributed to the regulation of cardiac inflammation and fibrosis.

Explore the active ingredients and mechanisms in Musa basjoo pseudostem juice against diabetes based on animal experiment, gas chromatography-mass spectrometer and network pharmacology

2021 ◽  
Vol 24 ◽  
Author(s):  
Feng Xu ◽  
Xiangpei Wang ◽  
Xiujuan Wei ◽  
Teng Chen ◽  
Hongmei Wu
Keyword(s):  
Gas Chromatography ◽  
Molecular Docking ◽  
Signaling Pathway ◽  
Mass Spectrometer ◽  
Diabetic Rats ◽  
Network Pharmacology ◽  
Receptor Interaction ◽  
Oral Glucose ◽  
Active Ingredients ◽  
Polar Parts

Background: Musa basjoo pseudostem juice (MBSJ) is a well-known Chinese medicine, and Miao people use MBSJ to treat diabetes. In this work, the active ingredients and molecular mechanism of MBSJ against diabetes were explored. Methods: Anti-diabetic activity of MBSJ was evaluated using diabetic rats, and then the ingredients in the small-polar parts of MBSJ were analyzed by gas chromatography-mass spectrometer (GC-MS). Targets were obtained from several databases to develop the "ingredient-target-disease" network by Cytoscape. A collaborative analysis was carried out using the tools in Cytoscape and R packages, and molecular docking was also performed. Results: MBSJ improved the oral glucose tolerance and insulin tolerance, and reduced fasting blood glucose, glycosylated hemoglobin, total cholesterol, triglyceride, and low-density lipoprotein levels in the serum of diabetic rats. 13 potential compounds were identified by GC-MS for subsequent analysis, including Dibutyl phthalate, Oleamide, Stigmasterol, Stigmast-4-en-3-one, etc. The anti-diabetic effect of MBSJ was related to multiple signaling pathways, including Neuroactive ligand-receptor interaction, Phospholipase D signaling pathway, Endocrine resistance, Rap1 signaling pathway, EGFR tyrosine kinase inhibitor resistance, etc. Molecular docking at least partially verified the screening results of network pharmacology. Conclusion: MBSJ had good anti-diabetic activity. The small-polar parts of MBSJ were rich in anti-diabetic active ingredients. Furthermore, the analysis results showed that the anti-diabetic effect of the small-polar parts of MBSJ may be the result of multiple components, multiple targets, and multiple pathways. The current research results can provide important support for studying the active ingredients and exploring the underlying mechanism of MBSJ against diabetes.

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