Integrated Network Pharmacology Analysis and Serum Metabolomics to Reveal the Anti-malaria Mechanism of Artesunate

Abstract

Artesunate is a widely used drug in clinical treatment of malaria. The aim of this study was to investigate the therapeutic mechanism of artesunate on malaria using an integrated strategy of network pharmacology and serum metabolomics. The mice models of malaria were established using 2 × 10 7 red blood cells infected with Plasmodium berghei ANKA injection. Giemsa and hematoxylin-eosin (HE) staining were used to evaluate the efficacy of artesunate on malaria. Next, network pharmacology analysis was applied to identify target genes. Then, a metabolomics strategy has been developed to find the possible significant serum metabolites and metabolic pathways induced by artesunate. Additionally, two parts of the results were integrated to confirm each other. Giemsa and HE staining results showed that artesunate significantly inhibited the proliferation of Plasmodium and reduced liver and spleen inflammation. Based on metabolomics, 18 differential endogenous metabolites were identified as potential biomarkers related to the artesunate for treating malaria. These metabolites were mainly involved in the relevant pathways of biosynthesis of unsaturated fatty acids; aminoacyl-tRNA biosynthesis; valine, leucine, and isoleucine biosynthesis; and phenylalanine, tyrosine, and tryptophan biosynthesis. The results of the network pharmacology analysis showed 125 potential target genes related to the treatment of malaria with artesunate. The functional enrichment was mainly associated with lipid and atherosclerosis; pathways of prostate cancer and proteoglycans in cancer; and PI3K-Akt, apoptosis, NF-κB, Th17 cell, and AGE-RAGE signaling pathways. These findings were partly consistent with the findings of the metabolism. Our results further suggested that artesunate could correct the inflammatory response caused by malaria through Th17 cell and NF-κB pathways. Meanwhile, our work revealed that cholesterol needed by Plasmodium berghei came directly from serum. Cholesterol and palmitic acid may be essential in the growth and reproduction of Plasmodium berghei . In summary, artesunate may have an effect on anti-malarial properties through multiple targets.

Effects of Evodiamine on Behavior and Hippocampal Neurons through Inhibition of Angiotensin-Converting Enzyme and Modulation of the Renin Angiotensin Pathway in a Mouse Model of Post-Traumatic Stress Disorder

“…We identified 43 differentially expressed metabolites that are frequently associated with PTSD-related pathways, including amino acid biosynthesis and the arachidonic acid metabolic pathway ( Figure 5 ). Subsequently, by integrating the results of metabolomics and network pharmacology and comprehensively exploring the underlying mechanisms [ 44 ], we observed that both KEGG pathway analyses included the renin secretion pathway ( Figure 6 A). Additionally, serum metabolomics revealed greater endocrine correlations in lipid metabolism pathways in both the SPS model group and the EVO-treated group.…”

Targeting the TRAF3-ULK1-NLRP3 regulatory axis to control alveolar macrophage pyroptosis in acute lung injury

“…A small piece of lung tissue was fixed in a 10% formalin solution, dehydrated, clarified, embedded in paraffin, and cut into 2-mmthick slices. Subsequently, liver tissue was stained with hematoxylin and eosin (H&E) (C0105M; Biyuntian, Shanghai, China), and observed under a Leitz Optilux light microscope (Leica, Wetzlar, Germany) [24].…”