Network Analysis, and Experimental Validation to Uncover the Mechanism of the Four Compounds in Artemisia annua (Qing Hao) Antimalarial

Abstract Background: Artemisinin is widely used to anti malaria, but the antimalaria mechanism and coordinative interaction of Artemisinin, Scopoletin, Arteannuin B and Artemisic acid are not clear. Methods: Based on the existing of antimalarial drugs, the antimalaria targets of Artemisinin, Scopoletin, Arteannuin B and Artemisic acid were explored by molecular docking with the similarity theory of chemical structure, and then the the antimalaria mechanism of Scopoletin and its coordinative antimalaria interaction of the mixture with the three other ingredients. Results: Then through using the text information excavation's method, the relevance proteins of antimalaria effect of Artemisinin were IL-6, ACHE, PC3, IPOB, CYC, TNF-α, UGT1A9, CASP3, XDH, IL-1β, VEGF, CAT, CREB, AMPK, UGT1A6, ADR, MAPK, COX2, LB24AB and CYP450. Meanwhile, the relevance proteins of Scopoletin were TNF-α, PI3K, IL-8, IL- 6, VEGF, IL-1β, MAPK, CD4, SP2, CTNNB, CASP3, PRO1400, IgE, IL-4, ICAM1, p38, STAT3, TLR4 and API4. But Arteannuin B and Artemisic acid had a little relevance with the above proteins. The interaction characteristic between TNF-a and Artemisia annua was the effect of the mixture of Artemisinin, Scopoletin, Arteannuin B and Artemisic acid was greater than Artemisinin, and the synergistic effect of the four elements was found in the progress of antimalaria. Conclusion: Antimalarial target of Artemisia annua ingredients was explored with data mining methods, and the antimalarial effect of Scopoletin may be related to TNF. Combined application of the four elements could achieve the same antimalarial effect and reduce the clinical usage of Artemisinin and Scopoletin.