2469-PUB: Exploring the Mechanisms of Berberine against Type 2 Diabetes Mellitus and Its Complications by Network Pharmacology

Diabetes ◽  
2019 ◽  
Vol 68 (Supplement 1) ◽  
pp. 2469-PUB
Author(s):  
SHA DI ◽  
LIN HAN ◽  
LINHUA ZHAO ◽  
XIAOLIN TONG
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Network Pharmacology

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 The Mechanism of Jinqi Jiangtang Tablet in Treatment of Type 2 Diabetes Mellitus Based on Network Pharmacology

2020 ◽  
Author(s):  
Mingjun Yang ◽  
Boni Song ◽  
Zhitong Bing ◽  
Juxiang Liu ◽  
Rui Li ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Drug Targets ◽  
Kegg Pathway ◽  
Enrichment Analysis ◽  
Network Pharmacology ◽  
Active Compounds ◽  
Online Tool

Abstract Background: Type 2 Diabetes Mellitus(T2DM) is an endocrine disease that caused mainly by insulin resistance (IR) and β cell dysfunction. The incidence of T2DM is quite high in the worldwide. To explore the molecular mechanism of Jinqi Jiangtang Tablet(JJT) in treating of T2DM based on Network Pharmacology. Methods: The active compounds, targets of three Traditional Chinese medicines in JJT were obtained by the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform（TCMSP） database and Uniprot database; The targets of T2DM were screened through the Drugbank database; The compound-target network was constructed via the Cytoscape 3.7.2 software and used the built-in Network analyzer to analyze and select the key active compounds; The overlapping targets of drug and disease targets were gained by the VENNY online tool and the targets were built by STRING website to select the key genes; Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway were performed on the potential targets using DAVID6.8 online tool to study the mechanism of overlapping targets. Via Systems Dock platform to validate the interaction between compound and targets Results: Twenty-five active compounds of JJT were screened, 101 drug targets, 142 disease targets and twenty-one overlapping targets. GO enrichment analysis showed that the biological processes (BP)mainly included the blood circulation ,etc. Cell composition(CC) mainly affected the integral component of plasma membrane, etc. Molecular functions(MF) mainly involved alpha-adrenergic receptor activity, etc. KEGG pathway analysis showed that there were twelve pathways related to T2DM, among which PPAR signaling pathway was related to T2DM mostly. RXRA is one of key targets of JJT and berberine performed well. Conclusions: This study revealed the mechanism of JJT in treatment of T2DM preliminarily and supplied a further foundation for studying its mechanism.

scholarly journals Integrated Analysis of the Mechanisms of Da-Chai-Hu Decoction in Type 2 Diabetes Mellitus by a Network Pharmacology Approach

2020 ◽  
Vol 2020 ◽  
pp. 1-21 ◽  
Author(s):  
Beida Ren ◽  
Ling Tan ◽  
Yiliang Xiong ◽  
Wenting Ji ◽  
Jie Mu ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Chinese Medicine ◽  
Traditional Chinese Medicine ◽  
Network Pharmacology ◽  
Integrated Analysis ◽  
Biological Processes ◽  
Active Components

Background. The incidence of type 2 diabetes mellitus (T2DM) has increased year by year, which not only seriously affects people’s quality of life, but also imposes a heavy economic burden on the family, society, and country. Currently, the pathogenesis, diagnosis, and treatment of T2DM are still unclear. Therefore, exploration of a precise multitarget treatment strategy is urgent. Here, we attempt to screen out the active components, effective targets, and functional pathways of therapeutic drugs through network pharmacology with taking advantages of traditional Chinese medicine (TCM) formulas for multitarget holistic treatment of diseases to clarify the potential therapeutic mechanism of TCM formulas and provide a systematic and clear thought for T2DM treatment. Methods. First, we screened the active components of Da-Chai-Hu Decoction (DCHD) by absorption, distribution, metabolism, excretion, and toxicity (ADME/T) calculation. Second, we predicted and screened the active components of DCHD and its therapeutic targets for T2DM relying on the Traditional Chinese Medicine Systems Pharmacology Analysis Platform (TCMSP database) and Text Mining Tool (GoPubMed database), while using the Database for Annotation, Visualization, and Integrated Discovery (DAVID) to obtain T2DM targets. Third, we constructed a network of the active component-target, target-pathway of DCHD using Cytoscape software (http://cytoscape.org/,ver.3.5.1) and then analyzed gene function, related biological processes, and signal pathways through the DAVID database. Results. We screened 77 active components from 1278 DCHD components and 116 effective targets from 253 ones. After matching the targets of T2DM, we obtained 38 important targets and 7 core targets were selected through further analysis. Through enrichment analysis, we found that these important targets were mainly involved in many biological processes such as oxidative stress, inflammatory reaction, and apoptosis. After analyzing the relevant pathways, the synthetic pathway for the treatment of T2DM was obtained, which provided a diagnosis-treatment idea for DCHD in the treatment of T2DM. Conclusions. This article reveals the mechanism of DCHD in the treatment of T2DM related to inflammatory response and apoptosis through network pharmacology, which lays a foundation for further elucidation of drugs effective targets.

scholarly journals HPLC-MS and Network Pharmacology Analysis to Reveal Quality Markers of Huo-Xue-Jiang-Tang Yin, a Chinese Herbal Medicine for Type 2 Diabetes Mellitus

2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
Qiugu Chen ◽  
Yuan Zhao ◽  
Maosheng Li ◽  
Ping Zheng ◽  
Shangbin Zhang ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Target Genes ◽  
Functional Enrichment ◽  
Network Pharmacology ◽  
Peptidase Activity ◽  
Active Components ◽  
Quality Markers

Huo-Xue-Jiang-Tang Yin (HXJTY) is a Chinese medicine formulation, which has been widely used for the treatment of various lipometabolism- and glycometabolism-related diseases in clinics. Currently, HXJTY is mainly prescribed to treat patients with type 2 diabetes mellitus (T2DM), yet its chemical and pharmacologic profiles remain to be elucidated. Here, the potential bioactive compound and action mechanism were investigated using chemical and network pharmacology analysis. A rapid HPLC-MS was employed to identify and quantify the component of HXJTY. On the basis of the identified chemical markers from HXJTY, a network pharmacology study, including target gene prediction and functional enrichment, was applied to screen out the main quality markers of HXJTY and explore its potential mechanism for the treatment of T2DM. The results showed that a total of 22 components were identified and quantified from HXJTY by HPLC-MS. Furthermore, 12 active components such as astragaloside IV, calycosin-7-O-β-D-glucoside, hydroxysafflor yellow A, and others were proposed as quality markers of HXJTY for treating T2DM based on network pharmacology analysis. In addition, 125 corresponding possible therapeutic target genes of T2DM were obtained. These target genes are mainly related to peptidase activity, hydrolase activity, phosphatase activity, and cofactor binding, suggesting the involvement of PI3K-Akt, MAPK, AGE-RAGE, and Rap1 signaling pathways in HXJTY-treated T2DM. Our results may provide a useful approach to identify potential quality markers and molecular mechanism of HXJTY for treating T2DM.

scholarly journals Constitution of a comprehensive phytochemical profile and network pharmacology based investigation to decipher molecular mechanisms of Teucrium polium L. in the treatment of type 2 diabetes mellitus

PeerJ ◽  
2020 ◽  
Vol 8 ◽  
pp. e10111
Author(s):  
Vahap Murat Kutluay ◽  
Neziha Yagmur Diker
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Signaling Pathway ◽  
Insulin Signaling ◽  
Molecular Mechanisms ◽  
Network Pharmacology ◽  
Teucrium Polium ◽  
Phytochemical Profile

Background Type 2 diabetes mellitus (T2DM) is a metabolic disease affecting a huge population worldwide. Teucrium polium L. has been used as a folk medicine for the treatment of T2DM in Anatolia, Turkey. The antihyperglycemic effect of the plant was reported previously. However, there was no detailed study on the underlying molecular mechanisms. In this study, we generated a research plan to clarify the active constituents of the extract and uncover the molecular mechanisms using network pharmacology analysis. Methods For this purpose, we composed a dataset of 126 compounds for the phytochemical profile of the aerial parts of T. polium. Drug-likeness of the compounds was evaluated, and 52 compounds were selected for further investigation. A total of 252 T2DM related targets hit by selected compounds were subjected to DAVID database. Results The KEGG pathway analysis showed enrichment for the TNF signaling pathway, insulin resistance, the HIF-1 signaling pathway, apoptosis, the PI3K-AKT signaling pathway, the FOXO signaling pathway, the insulin signaling pathway, and type 2 diabetes mellitus which are related to T2DM . AKT1, IL6, STAT3, TP53, INS, and VEGFA were found to be key targets in protein-protein interaction. Besides these key targets, with this study the role of GSK3β, GLUT4, and PDX1 were also discussed through literature and considered as important targets in the antidiabetic effect of T. polium. Various compounds of T. polium were shown to interact with the key targets activating PI3K-AKT and insulin signaling pathways. Conclusions According to these findings, mainly phenolic compounds were identified as the active components and IRS1/PI3K/AKT signaling and insulin resistance were identified as the main pathways regulated by T. polium. This study reveals the relationship of the compounds in T. polium with the targets of T2DM in human. Our findings suggested the use of T. polium as an effective herbal drug in the treatment of T2DM and provides new insights for further research on the antidiabetic effect of T. polium.

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