Exploring the molecular mechanism of ginseng against anthracycline-induced cardiotoxicity based on network pharmacology, molecular docking and molecular dynamics simulation.
Anthracycline-induced cardiotoxicity
Ginseng
Molecular docking
Network pharmacology
Journal
Hereditas
ISSN: 1601-5223
Titre abrégé: Hereditas
Pays: England
ID NLM: 0374654
Informations de publication
Date de publication:
06 Sep 2024
06 Sep 2024
Historique:
received:
02
06
2024
accepted:
01
09
2024
medline:
7
9
2024
pubmed:
7
9
2024
entrez:
6
9
2024
Statut:
epublish
Résumé
Previous clinical and basic studies have revealed that ginseng might have cardioprotective properties against anthracycline-induced cardiotoxicity (AIC). However, the underlying mechanism of ginseng action against AIC remains insufficiently understood. The aim of this study was to explore the related targets and pathways of ginseng against AIC using network pharmacology, molecular docking, cellular thermal shift assay (CETSA) and molecular dynamics (MD) simulations. Fourteen drug-disease common targets were identified. Enrichment analysis showed that the AGE-RAGE in diabetic complications, fluid shear stress and atherosclerosis, and TNF signaling pathway were potentially involved in the action of ginseng against AIC. Molecular docking demonstrated that the core components including Kaempferol, beta-Sitosterol, and Fumarine had notable binding activity with the three core targets CCNA2, STAT1, and ICAM1. Furthermore, the stable complex of STAT1 and Kaempferol with favorable affinity was further confirmed by CETSA and MD simulation. This study suggested that ginseng might exert their protective effects against AIC through the derived effector compounds beta-Sitosterol, Kaempferol and Fumarine by targeting CCNA2, STAT1, and ICAM1, and modulating AGE-RAGE in diabetic complications, fluid shear stress and atherosclerosis, and TNF signaling pathways.
Sections du résumé
BACKGROUND
BACKGROUND
Previous clinical and basic studies have revealed that ginseng might have cardioprotective properties against anthracycline-induced cardiotoxicity (AIC). However, the underlying mechanism of ginseng action against AIC remains insufficiently understood. The aim of this study was to explore the related targets and pathways of ginseng against AIC using network pharmacology, molecular docking, cellular thermal shift assay (CETSA) and molecular dynamics (MD) simulations.
RESULTS
RESULTS
Fourteen drug-disease common targets were identified. Enrichment analysis showed that the AGE-RAGE in diabetic complications, fluid shear stress and atherosclerosis, and TNF signaling pathway were potentially involved in the action of ginseng against AIC. Molecular docking demonstrated that the core components including Kaempferol, beta-Sitosterol, and Fumarine had notable binding activity with the three core targets CCNA2, STAT1, and ICAM1. Furthermore, the stable complex of STAT1 and Kaempferol with favorable affinity was further confirmed by CETSA and MD simulation.
CONCLUSIONS
CONCLUSIONS
This study suggested that ginseng might exert their protective effects against AIC through the derived effector compounds beta-Sitosterol, Kaempferol and Fumarine by targeting CCNA2, STAT1, and ICAM1, and modulating AGE-RAGE in diabetic complications, fluid shear stress and atherosclerosis, and TNF signaling pathways.
Identifiants
pubmed: 39243097
doi: 10.1186/s41065-024-00334-y
pii: 10.1186/s41065-024-00334-y
doi:
Substances chimiques
Anthracyclines
0
Sitosterols
0
gamma-sitosterol
5LI01C78DD
STAT1 Transcription Factor
0
Kaempferols
0
kaempferol
731P2LE49E
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
31Informations de copyright
© 2024. The Author(s).
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