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 treat malaria, but the antimalarial mechanism and coordinative interactions governing the actions of artemisinin, scopoletin, arteannuin B and artemisinic acid have not been elucidated. Methods: Based on the existence of antimalarial drugs, the antimalaria targets of artemisinin, scopoletin, arteannuin B and artemisinic acid were investigated by molecular docking using the similarity theory of chemical structure, and the antimalaria mechanism of scopoletin and its coordinative antimalaria interactions with the other three ingredients of the mixture were subsequently examined. Results: Using the text information excavation method, the relevant proteins involved in the antimalarial 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. The relevant proteins involved in the antimalarial effect 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. However, arteannuin B and artemisinic acid had little relevance to the abovementioned proteins. The interaction property between TNF-α and Artemisia annua was that the effect of the mixture of artemisinin, scopoletin, arteannuin B and artemisinic acid was greater than that of artemisinin alone, and the synergistic effect of the four elements was considered beneficial to the progress of antimalarial treatment. Conclusion: The antimalarial targets of Artemisia annua ingredients were examined using data mining methods, and the antimalarial effect of scopoletin may be related to TNF. The combined application of the four elements achieved the same antimalarial effect and reduced the clinical use of artemisinin and scopoletin.