Integrating Network Pharmacology and Experimental Validation to Decipher the Mechanism of Action of Huanglian Jiedu Decoction in Treating Atherosclerosis

Abstract

Background This study used network pharmacology, molecular docking and experimental validation to assess the effects of Huanglian Jiedu Decoction (HLJDD) on atherosclerosis (AS). Methods The components and targets of HLJDD were analyzed using the Traditional Chinese Medicine Systems Pharmacology database, and information on the genes associated with AS was retrieved from the GeneCards and OMIM platforms. Protein–protein interactions were analyzed using the STRING platform. A component–target–disease network was constructed using Cytoscape. GO and KEGG analyses were performed to identify molecular biological processes and signaling pathways, and the predictions were verified experimentally. Molecular docking was conducted with ChemOffice software, PyMOL software and Vina to verify the correlation of targets and compounds. Results HLJDD contained 31 active compounds, with quercetin, kaempferol, moupinamide and 5-hydroxy-7-methoxy-2-(3,4,5-trimethoxyphenyl)chromone as the core compounds. The most important biotargets of HLJDD in AS were ICAM-1, CD31 and RAM-11. The molecular docking results showed that the molecular docking interaction energy between the 3 key targets and the 4 high-degree components were much less than −5 kJ∙mol −1 . The experimental validation results showed that HLJDD might treat AS mainly by reducing TC, TG and LDL-C and increasing HDL-C, upregulating CD31 expression, reducing ICAM-1 and RAM-11 expression, and downregulating inflammatory factors, including CRP, IL-6 and TNF-α. These results support the network pharmacology data and demonstrate that HLJDD affects the expression of core genes and alters the leukocyte transendothelial migration signaling pathway. Conclusion Based on network pharmacology and experimental validation, our study indicated that HLJDD exerted anti-AS effect through upregulating CD31 expression and reducing the expression of ICAM-1 and RAM-11. HLJDD may be a potential therapeutic drug to the prevention of AS.

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“…html) (Huang et al, 2020). In addition, these overlapping targets were introduced into the STRING database (https://www.stringdb.org/) to investigate protein-protein interaction (PPI) relationships; this allowed us to identify targets that were closely related to insomnia (Liang et al, 2021); the protein interaction selection score was set to >0.6. Cytoscape version 3.6.1 software (Free Software Foundation, Inc., Boston, MA, United States) was used to visualize the PPI network.…”

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“…The findings of this investigation are consistent with Bahriz et al (2021) and Ishii (2022) who had discovered that there was a considerable change in lipid characteristics in rabbits that had been given cholesterol, and then treated with pioglitazone, and this may be due to that pioglitazone decreases the cholesterol levels through improving the cholesterol clearance from the circulation. This is most likely accomplished by an increase in lipoprotein lipase-mediated lipolysis, and treatment with pioglitazone for an extended period of time resulted in sustained improvements in both triglyceride and HDL-C levels (Figures 4, 5) [14]. Aortic SOD level was dramatically decreased by pioglitazone indicating a reduction in ROS and the ensuing lipid peroxidation.…”

Mechanism analysis of Buyang Huanwu decoction in treating atherosclerosis based on network pharmacology and in vitro experiments

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