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.
Highlights
Inflammation is the body’s protective response to injury or infection, but insufficient or excessive inflammation increases the incidence of many diseases [1]
Ephedra has been widely used to treat asthma in Asia; a strategy of network pharmacology combined with molecular docking and in vitro experiments was performed to predict the anti-inflammatory targets of ephedra in treating asthma; the results showed that SELE, IL-2, and CXCL10 are critical targets for ephedra against inflammation due to asthma [16]
The anti-inflammatory chemical components of Lonicerae japonicae flos (LJF) were gathered from NCBI and PubMed, and a total of 29 components with high content in which were screened for network pharmacology and molecular docking analysis [18,19,20,21,22,23,24,25,26,27,28,29,30,31,32,33,34,35,36,37,38,39]
Summary
Inflammation is the body’s protective response to injury or infection, but insufficient or excessive inflammation increases the incidence of many diseases [1]. In the process of the inflammatory response, cytokines play an important bidirectional regulatory role. In the early stage of inflammation, proinflammatory cytokines, such as TNF-α, IL-8, IL1β, and IFN-γ, are predominant, which can eliminate the threat of infection or trauma through activating a variety of immune cells and promoting the inflammatory response. In the late stage of inflammation, anti-inflammatory cytokines such as IL-10 and IL-13 are dominant, which can weaken and control the inflammatory response [2]. In some special cases, the bidirectional regulation pathway of cytokines is damaged, and proinflammatory cytokines continue to play their roles, leading to a large number of immune cells being activated in some parts of the body and even forming inflammatory storms ( known as cytokine storms) in severe cases [3]. Inflammatory storms may be one of the leading causes of severe complications and death in severely affected patients for some acute respiratory infections, such as COVID-19, SARS-COV (SARS), MERS-COV (Middle East respiratory syndrome), and influenza [4,5,6]
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