Abstract
Xiebai San (XBS) is a traditional Chinese medicine (TCM) prescription that has been widely used to treat pediatric pneumonia since the Song dynasty. To reveal its underlying working mechanism, a network pharmacology approach was used to predict the active ingredients and potential targets of XBS in treating pediatric pneumonia. As a result, 120 active ingredients of XBS and 128 potential targets were screened out. Among them, quercetin, kaempferol, naringenin, licochalcone A and isorhamnetin showed to be the most potential ingredients, while AKT1, MAPK3, VEGFA, TP53, JUN, PTGS2, CASP3, MAPK8 and NF-κB p65 showed to be the most potential targets. IL-17 signaling pathway, TNF signaling pathway and PI3K-Akt signaling pathway, which are involved in anti-inflammation processes, immune responses and apoptosis, showed to be the most probable pathways regulated by XBS. UPLC-Q/Orbitrap HRMS analysis was then performed to explore the main components of XBS, and liquiritin, quercetin, kaempferol, licochalcone A and glycyrrhetinic acid were identified. Molecular docking analysis of the compounds to inflammation-associated targets revealed good binding abilities of quercetin, kaempferol, licochalcone A and liquiritin to NF-κB p65 and of quercetin and kaempferol to Akt1 or Caspase-3. Moreover, molecular dynamics (MD) simulation for binding of quercetin or kaempferol to NF-κB p65 revealed dynamic properties of high stability, high flexibility and lowbinding free energy. In the experiment with macrophages, XBS markedly suppressed the (Lipopolysaccharides) LPS-induced expression of NF-κB p65 and the production of pro-inflammatory cytokines IL-6 and IL-1β, supporting XBS to achieve an anti-inflammatory effect through regulating NF-κB p65. XBS also down-regulated the expression of p-Akt (Ser473)/Akt, Bax and Caspase-3 and up-regulated the expression of Bcl-2, indicating that regulating Akt1 and Caspase-3 to achieve anti-apoptotic effect is also the mechanism of XBS for treating pediatric pneumonia. Our study helped to reveal the pharmacodynamics material basis as well as the mechanism of XBS in treating pediatric pneumonia.
Highlights
Pneumonia is a rather common childhood condition mainly caused by bacteria, viruses, or fungi infection leading to children fighting for breath as their lungs fill with pus and fluid (Quinton et al, 2018)
Our results provided a scientific basis for the clinical use of Xiebai San (XBS) for treating pediatric pneumonia
The results suggested that the anti-inflammatory effect of XBS in RAW 264.7 cells might be achieved through inhibiting cell apoptosis, and confirmed that the PI3K/Akt signaling pathway predicted by the network pharmacology analysis plays an important role in XBS against pediatric pneumonia
Summary
Pneumonia is a rather common childhood condition mainly caused by bacteria, viruses, or fungi infection leading to children fighting for breath as their lungs fill with pus and fluid (Quinton et al, 2018). Pneumonia is still the leading cause of morbidity and mortality in children under the age of five (Gupta, 2012; Goodman et al, 2019), claiming the lives of approximately 700,000 to 900,000 children every year (Troeger et al, 2017; WHO World Health Organisation Geneva, 2018). Streptococcus pneumoniae is the most commonly identified organism that causes bacterial pneumonia in children under five (GBD 2016 Lower Respiratory Infections Collaborators, 2016). Antibiotic medications can treat most bacterial pneumonias, but do not work on viruses and fungal pneumonias. Novel and safe treatment strategies for pediatric pneumonia are urgently required
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
