An Integrated Approach Based on Network Pharmacology Combined with Experimental Verification Reveals AMPK/PI3K/Akt Signaling is an Important Way for the Anti-Type 2 Diabetic Activity of Silkworm Excrement

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Abstract

Objective

This study was aimed to investigate the potential active components, targets and mechanisms of silkworm excrement (SE) in the treatment of type 2 diabetes mellitus (T ₂D) based on THE network pharmacology combined with experimental verification.

Methods

Firstly, the inhibitory effects of SE on α-glucosidase were measured in vitro. Then, the potential active components and potential targets of SE and the targets of T ₂D were collected and screened using bioinformatics databases. Then, the R language, Cytoscape, Perl software were used to screen and visualize important components, targets, biological processes and signaling pathways. Finally, the predicted results by network pharmacology were verified via glucose absorption assay, oil red O staining assay and Western blot assay.

Results

Our results showed SE effectively inhibited the activities of α-glucosidase. The results of network pharmacology suggested there were 33 potential active ingredients and 42 potential targets in SE. The molecular pathways of SE against T ₂D were further predicted, including response to insulin-like growth factor receptor binding, protein serine/threonine kinase activity, and MAP kinase activity. KEGG pathway analyses predicted potential targets were involved in multiple signaling pathways, such as insulin signaling pathway, insulin resistance pathway and AMPK signaling pathway. In IR HepG2 cells, SE treatments increased glucose consumption and decreased lipogenesis. The insulin resistance (IR)-related AMPK/PI3K/AKT signaling was further studied and the results showed SE could significantly up-regulate the phosphorylation levels of AMPK, PI3K, and Akt proteins in IR-HepG2 cells.

Conclusion

Our results suggested AMPK/PI3K/Akt signaling is an important way for the anti-type 2 diabetic activity of silkworm excrement by using an integrated approach based on network pharmacology combined with experimental verification.

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Most cited references 37

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Cytoscape: a software environment for integrated models of biomolecular interaction networks.

Paul Shannon, Andrew Markiel, Owen Ozier … (2003)

Cytoscape is an open source software project for integrating biomolecular interaction networks with high-throughput expression data and other molecular states into a unified conceptual framework. Although applicable to any system of molecular components and interactions, Cytoscape is most powerful when used in conjunction with large databases of protein-protein, protein-DNA, and genetic interactions that are increasingly available for humans and model organisms. Cytoscape's software Core provides basic functionality to layout and query the network; to visually integrate the network with expression profiles, phenotypes, and other molecular states; and to link the network to databases of functional annotations. The Core is extensible through a straightforward plug-in architecture, allowing rapid development of additional computational analyses and features. Several case studies of Cytoscape plug-ins are surveyed, including a search for interaction pathways correlating with changes in gene expression, a study of protein complexes involved in cellular recovery to DNA damage, inference of a combined physical/functional interaction network for Halobacterium, and an interface to detailed stochastic/kinetic gene regulatory models.

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Global aetiology and epidemiology of type 2 diabetes mellitus and its complications

Sylvia Ley, Yan Zheng, Frank Hu (2017)

Globally, the number of people with diabetes mellitus has quadrupled in the past three decades, and diabetes mellitus is the ninth major cause of death. About 1 in 11 adults worldwide now have diabetes mellitus, 90% of whom have type 2 diabetes mellitus (T2DM). Asia is a major area of the rapidly emerging T2DM global epidemic, with China and India the top two epicentres. Although genetic predisposition partly determines individual susceptibility to T2DM, an unhealthy diet and a sedentary lifestyle are important drivers of the current global epidemic; early developmental factors (such as intrauterine exposures) also have a role in susceptibility to T2DM later in life. Many cases of T2DM could be prevented with lifestyle changes, including maintaining a healthy body weight, consuming a healthy diet, staying physically active, not smoking and drinking alcohol in moderation. Most patients with T2DM have at least one complication, and cardiovascular complications are the leading cause of morbidity and mortality in these patients. This Review provides an updated view of the global epidemiology of T2DM, as well as dietary, lifestyle and other risk factors for T2DM and its complications.

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Global estimates of diabetes prevalence for 2013 and projections for 2035.

L Guariguata, D.R. Whiting, I Hambleton … (2014)

Diabetes is a serious and increasing global health burden and estimates of prevalence are essential for appropriate allocation of resources and monitoring of trends. We conducted a literature search of studies reporting the age-specific prevalence for diabetes and used the Analytic Hierarchy Process to systematically select studies to generate estimates for 219 countries and territories. Estimates for countries without available source data were modelled from pooled estimates of countries that were similar in regard to geography, ethnicity, and economic development. Logistic regression was applied to generate smoothed age-specific prevalence estimates for adults 20-79 years which were then applied to population estimates for 2013 and 2035. A total of 744 data sources were considered and 174 included, representing 130 countries. In 2013, 382 million people had diabetes; this number is expected to rise to 592 million by 2035. Most people with diabetes live in low- and middle-income countries and these will experience the greatest increase in cases of diabetes over the next 22 years. The new estimates of diabetes in adults confirm the large burden of diabetes, especially in developing countries. Estimates will be updated annually including the most recent, high-quality data available. Copyright © 2013. Published by Elsevier Ireland Ltd.

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Author and article information

Journal

Journal ID (nlm-ta): Diabetes Metab Syndr Obes

Journal ID (iso-abbrev): Diabetes Metab Syndr Obes

Journal ID (publisher-id): dmso

Journal ID (pmc): dmso

Title: Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy

Publisher: Dove

ISSN (Electronic): 1178-7007

Publication date (Electronic): 11 February 2021

Publication date Collection: 2021

Volume: 14

Pages: 601-616

Affiliations

[1 ]School of Pharmacy, Chengdu University of Traditional Chinese Medicine , Chengdu, 611137, People’s Republic of China

Author notes

Correspondence: Wei Peng; Chunjie Wu School of Pharmacy, Chengdu University of Traditional Chinese Medicine , No. 1166, Liutai Avenue, Chengdu, 611137, People’s Republic of ChinaTel +86-028-61801001 Email pengwei@cdutcm.edu.cn; wucjcdtcm@163.com

[*]

These authors contributed equally to this work

Author information

Chunjie Wu http://orcid.org/0000-0001-7496-8469

Article

Publisher ID: 291638

DOI: 10.2147/DMSO.S291638

PMC ID: 7887153

PubMed ID: 33603425

SO-VID: 1b422492-8cf7-4dac-b831-3892184f95c7

License:

This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms ( https://www.dovepress.com/terms.php).

History

Date received : 11 November 2020

Date accepted : 11 January 2021

Page count

Figures: 10, Tables: 1, References: 37, Pages: 16

Funding

Funded by: the Project of Administration of Traditional Chinese Medicine of Sichuan Province of China;

Funded by: Xinglin Scholar Discipline Promotion Talent Program of Chengdu University of Traditional Chinese Medicine;

Funded by: Chengdu University of Traditional Chinese Medicine Key Laboratory of Systematic Research of Distinctive Chinese Medicine Resources in Southwest China;

This research was supported by the Project of Administration of Traditional Chinese Medicine of Sichuan Province of China (No. 2020HJZX001), Xinglin Scholar Discipline Promotion Talent Program of Chengdu University of Traditional Chinese Medicine (No. BSH2018006), and Project of Open Research Fund of Chengdu University of Traditional Chinese Medicine Key Laboratory of Systematic Research of Distinctive Chinese Medicine Resources in Southwest China (No. 2020XSGG021).

An Integrated Approach Based on Network Pharmacology Combined with Experimental Verification Reveals AMPK/PI3K/Akt Signaling is an Important Way for the Anti-Type 2 Diabetic Activity of Silkworm Excrement

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Abstract

Objective

Methods

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Conclusion

Related collections

GLUT4 biology

Most cited references 37

Cytoscape: a software environment for integrated models of biomolecular interaction networks.

Global aetiology and epidemiology of type 2 diabetes mellitus and its complications

Global estimates of diabetes prevalence for 2013 and projections for 2035.

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