RESUMEN
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-1ß, 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.
RESUMEN
OBJECTIVE: To assess the current status on re-evaluation of marketed drug in China since the promulgation of drug law in 1985. METHODS: Review of literature on Chinese pharmaceutical abstract and CBMdisc from 1985 to 2001 year was done. RESULTS: 4029 papers and 855 marketed drugs from 1985 to 2001 were included. Drugs on anti-infection agent, cardiovascular system and digestive system were the main drugs being re-evaluated, with the proportions of 27.1%, 20.1% and 11.1% respectively. The amounts of both marketed drugs and literature were increasing year by year. The method used for re-evaluation were random and non-random clinical trial. 41.4% of all the samples had a sample size of 50 - 100 research subjects. There were 13 papers with more than 5000 samples. The level on evidence based literature was assessed. 44 papers were graded as first class, and 182 papers the second, 2466 papers the third and 1337 papers the fourth. The quality of literature was improved year by year. CONCLUSION: The amount, quality as well as the sample size of literature being re-evaluated on marketed drug were increased from 1985 to 2001. However, the design and evaluation of those trials were not standardized.