Abstract

Objective:To explore the potential molecular mechanism ofLycii Cortexin treating type 2 diabetes mellitus (T2DM) by virtue of network pharmacology and molecular docking method.Methods: Ingredients ofLycii Cortexwere collected from TCMSP and BATMAN-TCM databases, and the corresponding targets and T2DM-related targets were obtained respectively from SwissTargetPrediction and GenCards databases. Venn diagram was applied to derive the potential active components and effect targets ofLycii Cortexin the treatment of T2DM. GO enrichment analysis and KEGG pathway analysis were performed in the database of DAVID. Cytoscape 3.6.1 was used to produce the “core components-core targets” network. The molecular docking between core components and core targets was implemented through Autodock Vina.Results:Six core components and twelve core targets ofLycii Cortexin treating T2DM were identified. GO enrichment analysis and KEGG pathway analysis suggested the following signaling pathways and biological processes were involved in the treatment of T2DM byLycii Cortex: PI3K-Akt signaling pathway, TNF signaling pathway, HIF-1 signaling pathway, Toll-like receptor signaling pathway, NOD-like receptor signaling pathway, and peptidyl-threonine phosphorylation, the positive regulation of cyclase activity, the positive regulation of genetic expression, and lipoprotein translocation. The binding results demonstrated a relatively high affinity between core components ofLycii Cortex, including kulactone, hederagenin, scopolin, etc., and core targets, containing IL6, PPARγ, TNF, and mTOR, indicating the efficacy ofLycii Cortexin treating T2DM.Conclusion:Lycii Cortexplays a role in the treatment of T2DM with its ingredients such as kulactone, linarin, hederagenin, and scopolin regulating glycometabolism, affecting cell apoptosis and weakening inflammatory response through targets like IL6, PPARγ, TNF, and mTOR.

Highlights

  • Diabetic Mellitus (DM) serves as one type of metabolic disease directly triggered by genetic factors and coinduced by a series of external factors such as environment and dietary habit[1]

  • The results of the “core components-targets-pathway” network demonstrated that ingredients of Lycii Cortex such as kulactone, linarin, and hederagenin probably played a role in the treatment of type 2 diabetes mellitus (T2DM) through regulating T2DM signaling pathway, PI3K-Akt signaling pathway, tumor necrosis factor (TNF) signaling pathway, HIF-1 signaling pathway, MAPK signaling pathway, etc., via core targets like glyceraldehyde-3-phosphate dehydrogenase (GAPDH), interleukin 6 (IL6), TNF, and mitogen-activated protein kinase 3 (MAPK3)

  • This study totally identified 15 active components of Lycii Cortex from databases and different components might play a collaborative role in the treatment of T2DM

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Summary

INTRODUCTION

Diabetic Mellitus (DM) serves as one type of metabolic disease directly triggered by genetic factors and coinduced by a series of external factors such as environment and dietary habit[1]. The combined application of network pharmacology and molecular docking technology has emerged as a productive tool in investigating the material basis and mechanism of traditional Chinese medicine and compound medicine in disease treatment[17]. On this basis, this study is designed to predict the potential active components, effect targets, and mechanism of Lycii Cortex in treating T2DM by adopting network pharmacology and molecular docking technique with the intention of providing certain foundation for future research on the clinical application and in-depth development of Lycii Cortex. The common targets gained by overlapping targets related to the active components of Lycii Cortex and T2DM targets using the online tool, Image GP (http://www.ehbio.com/Image GP/) were taken as the potential therapeutic targets of Lycii Cortex in the treatment of T2DM

Enrichment Analysis
Network Construction
Potential Active Components of Lycii Cortex
Molecular Docking
Results
Construction of Potential Targets Base
Network Construction and Analysis
Molecular Docking Analysis
Discussion
Active Components of Lycii Cortex in Treating T2DM
Core Targets of Lycii Cortex in Treating T2DM
Mechanism of Lycii Cortex in Treating T2DM
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