Network Pharmacology-Based Identification of Potential Targets of Lonicerae japonicae Flos Acting on Anti-Inflammatory Effects.

Abstract

Lonicerae japonicae flos (LJF) is widely used for the treatment of inflammation-related diseases in traditional Chinese medicine (TCM). To clarify the anti-inflammatory mechanism of LJF, 29 compounds with high content in LJF were selected for network pharmacology. Then, a comprehensive network pharmacology strategy was implemented, which involved compound-inflammation-target construction, protein-protein interaction (PPI) network analysis, and enrichment analysis. Finally, molecular docking and in vitro experiments were performed to verify the anti-inflammatory activity and targets of the key compound. As a result, 279 inflammation-associated proteins were identified, which are mainly involved in the AGE/RAGE signaling pathway in diabetic complications, the HIF-1 signaling pathway, the PI3K-AKT signaling pathway, and EGFR tyrosine kinase inhibitor resistance. A total of 12 compounds were linked to more than 35 targets, including apigenin, kaempferol, quercetin, luteolin, and ferulic acid. The results of molecular docking showed that AKT has the most binding activity, exhibiting certain binding activity with 10 compounds, including vanillic acid, protocatechuic acid, secologanic acid, quercetin, and luteolin; the results of qRT-PCR and WB confirmed that two key compounds, secologanic acid and luteolin, could significantly decrease the secretion of TNF-α and the AKT expression of RAW264.7 murine macrophages stimulated by LPS (lipopolysaccharide). These results demonstrate that the comprehensive strategy can serve as a universal method to illustrate the anti-inflammatory mechanisms of traditional Chinese medicine by identifying the pathways or targets.

• Authors: Xiaoying Guo, Xiao Yu, Bingqing Zheng, Longfei Zhang, Fang Zhang, Yongqing Zhang, Jia Li, Gaobin Pu, Lijun Zhang, Haifeng Wu
• Journal: BioMed research international (Biomed Res Int) Vol. 2021 Pg. 5507003 ( 2021) ISSN: 2314-6141 [Electronic] United States
• PMID: 34595237 (Publication Type: Journal Article)
• Copyright: Copyright © 2021 Xiaoying Guo et al.

Chemical References

• Anti-Inflammatory Agents
• Iridoids
• Plant Extracts
• RNA, Messenger
• Tumor Necrosis Factor-alpha
• secologanic acid
• lonicerae flos
• Proto-Oncogene Proteins c-akt
• Luteolin

Topics

• Animals
• Anti-Inflammatory Agents (chemistry, pharmacology)
• Down-Regulation (drug effects, genetics)
• Gene Ontology
• Gene Regulatory Networks (drug effects)
• Iridoids (pharmacology)
• Lonicera (chemistry)
• Luteolin (pharmacology)
• Mice
• Molecular Docking Simulation
• Molecular Targeted Therapy
• Network Pharmacology
• Phosphorylation (drug effects)
• Plant Extracts (chemistry, pharmacology)
• Protein Interaction Maps
• Proto-Oncogene Proteins c-akt (metabolism)
• RAW 264.7 Cells
• RNA, Messenger (genetics, metabolism)
• Thermodynamics
• Tumor Necrosis Factor-alpha (biosynthesis, genetics)