关键词: 苹果, 溶血所致高胆红素血症, 网络药理学, 机制

Abstract: Objective:To investigate the mechanism of action of apple on hemolytic jaundice through network pharmacology, molecular docking and experimental validation; Methods: A network pharmacology approach was used to predict the possible active ingredients and potential targets of apple active ingredients for the treatment of hemolysis-induced hyperbilirubinemia, as well as the pathways and biological processes of potential target enrichment, and to construct a "disease-pathway-active-component-target" for apple; Autodock software was used to perform molecular docking of key active ingredients and potential targets to verify the reliability of network analysis results; and to construct an animal experimental model of hemolysis-induced hyperbilirubinemia in rats to investigate the effect of apple alcohol extract on hemolysis-induced hyperbilirubinemia. Results: The network pharmacological analysis was conducted to collect and collate 17 active ingredients of apple with high oral absorption and excellent drug-like properties, among which quercetin, 2α-hydroxyursolic acid, β-sitosterol, Phloretin, epicatechin, play an important contribution in the treatment of hemolysis-induced hyperbilirubinemia.Degree ranked top 5 core targets of AKT1, VEGFA, EGFR, SRC, and STATS3 interact with each other through bile secretion, HIF-1 signaling pathway, TNF signaling pathway and NF-kappa B signaling pathway to exert therapeutic effects. Molecular docking of the main active ingredient and the core target screened by the network, with a binding energy <-4.0 kcal-mol-1 showed a strong affinity between the active ingredient screened by Apple and the potential target obtained for the treatment of hemolysis-induced hyperbilirubinemia, with reliable results from the network analysis; The animal experiment results indicated that the model group was compared with the control group with low HB group in blood (p < 0.01), TB, IB, ALT, AST, TNF, IL-6 indexes of serum liver function were and inflammatory factors were higher than the blank control group (p < 0.01); the model control group was significantly lower compared with other groups (p < 0.05). After the intervention with apple the experimental group had higher HB levels and decreased TB, IB, ALT, AST, TNF, IL-6 compared with the model group experimental animals. Conclusion: The apple may reduce hyperbilirubinemia due to hemolysis and may provide a basis for research on non-invasive therapy for neonatal jaundice.

Key words: Apple, Hemolytic jaundice caused by hemolysis, Network pharmacology, Mechanism