Molecular Mechanism of the Effect of Huanglian Jiedu Decoction on Type 2 Diabetes Mellitus Based on Network Pharmacology and Molecular Docking.
Apoptosis
China
Cluster Analysis
Diabetes Mellitus, Type 2
/ drug therapy
Drugs, Chinese Herbal
/ analysis
Flavanones
/ analysis
Flavonoids
/ analysis
Gene Expression Profiling
Humans
Inflammation
Interleukin-6
/ metabolism
Kaempferols
/ analysis
Medicine, Chinese Traditional
Molecular Docking Simulation
Protein Interaction Mapping
Proto-Oncogene Proteins c-akt
/ metabolism
Quercetin
/ analysis
Journal
Journal of diabetes research
ISSN: 2314-6753
Titre abrégé: J Diabetes Res
Pays: England
ID NLM: 101605237
Informations de publication
Date de publication:
2020
2020
Historique:
received:
31
03
2020
revised:
06
07
2020
accepted:
13
07
2020
entrez:
2
11
2020
pubmed:
3
11
2020
medline:
28
9
2021
Statut:
epublish
Résumé
Huanglian Jiedu Decoction (HLJDD) is a Traditional Chinese Medicine (TCM) formula comprising four herbal medicines. This decoction has long been used in China for clinically treating T2DM. However, the molecular mechanism of HLJDD treat for T2DM is still not fully known. Hence, this study was designed to reveal the synergistic mechanism of HLJDD formula in the treatment of T2DM by using network pharmacology method and molecular docking. Retrieving and screening of active components of different herbs in HLJDD and corresponding T2DM-related target genes across multiple databases. Subsequently, STRING and Cytoscape were applied to analysis and construct PPI network. In addition, cluster and topological analysis were employed for the analysis of PPI networks. Then, the GO and KEGG enrichment analysis were performed by using ClueGO tool. Finally, the differentially expressed analysis was used to verify whether the expression of key target genes in T2DM and non-T2DM samples was statistically significant, and the binding capacity between active components and key targets was validated by molecular docking using AutoDock. There are 65 active components involved in 197 T2DM-related targets that are identified in HLJDD formula. What is more, 39 key targets (AKT1, IL-6, FOS, VEGFA, CASP3, etc.) and 3 clusters were obtained after topological and cluster analysis. Further, GO and KEGG analysis showed that HLJDD may play an important role in treating T2DM and its complications by synergistically regulating many biological processes and pathways which participated in signaling transduction, inflammatory response, apoptotic process, and vascular processes. Differentially expressed analysis showed that AKT1, IL-6, and FOS were upregulated in T2DM samples and a significant between sample differential expression. These results were validated by molecular docking, which identified 5 high-affinity active components in HLJDD, including quercetin, wogonin, baicalein, kaempferol, and oroxylin A. Our research firstly revealed the basic pharmacological effects and relevant mechanisms of the HLJDD in the treatment of T2DM and its complications. The prediction results might facilitate the development of HLJDD or its active compounds as alternative therapy for T2DM. However, more pharmacological experiments should be performed for verification.
Sections du résumé
BACKGROUND
BACKGROUND
Huanglian Jiedu Decoction (HLJDD) is a Traditional Chinese Medicine (TCM) formula comprising four herbal medicines. This decoction has long been used in China for clinically treating T2DM. However, the molecular mechanism of HLJDD treat for T2DM is still not fully known. Hence, this study was designed to reveal the synergistic mechanism of HLJDD formula in the treatment of T2DM by using network pharmacology method and molecular docking.
METHODS
METHODS
Retrieving and screening of active components of different herbs in HLJDD and corresponding T2DM-related target genes across multiple databases. Subsequently, STRING and Cytoscape were applied to analysis and construct PPI network. In addition, cluster and topological analysis were employed for the analysis of PPI networks. Then, the GO and KEGG enrichment analysis were performed by using ClueGO tool. Finally, the differentially expressed analysis was used to verify whether the expression of key target genes in T2DM and non-T2DM samples was statistically significant, and the binding capacity between active components and key targets was validated by molecular docking using AutoDock.
RESULTS
RESULTS
There are 65 active components involved in 197 T2DM-related targets that are identified in HLJDD formula. What is more, 39 key targets (AKT1, IL-6, FOS, VEGFA, CASP3, etc.) and 3 clusters were obtained after topological and cluster analysis. Further, GO and KEGG analysis showed that HLJDD may play an important role in treating T2DM and its complications by synergistically regulating many biological processes and pathways which participated in signaling transduction, inflammatory response, apoptotic process, and vascular processes. Differentially expressed analysis showed that AKT1, IL-6, and FOS were upregulated in T2DM samples and a significant between sample differential expression. These results were validated by molecular docking, which identified 5 high-affinity active components in HLJDD, including quercetin, wogonin, baicalein, kaempferol, and oroxylin A.
CONCLUSION
CONCLUSIONS
Our research firstly revealed the basic pharmacological effects and relevant mechanisms of the HLJDD in the treatment of T2DM and its complications. The prediction results might facilitate the development of HLJDD or its active compounds as alternative therapy for T2DM. However, more pharmacological experiments should be performed for verification.
Identifiants
pubmed: 33134394
doi: 10.1155/2020/5273914
pmc: PMC7593729
doi:
Substances chimiques
Drugs, Chinese Herbal
0
Flavanones
0
Flavonoids
0
IL6 protein, human
0
Interleukin-6
0
Kaempferols
0
huanglian-jie-du decoction
0
baicalein
49QAH60606
5,7-dihydroxy-6-methoxy-2-phenylchromen-4-one
53K24Z586G
kaempferol
731P2LE49E
Quercetin
9IKM0I5T1E
AKT1 protein, human
EC 2.7.11.1
Proto-Oncogene Proteins c-akt
EC 2.7.11.1
wogonin
POK93PO28W
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
5273914Informations de copyright
Copyright © 2020 Bei Yin et al.
Déclaration de conflit d'intérêts
The authors declare that they have no conflicts of interest.
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