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

作者：Feiran Wang, Song Jian, Yingying Yan, Qian Zhou, Xiaojing Li, Ping Wang, Zongtong Yang, Qiuhong Zhang, Huimin Zhang · 发表于：ACS Omega · 年份：2022 · DOI：10.1021/acsomega.2c04157 · 被引用次数：9 · 研究领域：Computational Drug Discovery Methods、Malaria Research and Control、Metabolomics and Mass Spectrometry Studies

High Resolution Image Download MS PowerPoint Slide 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 fun...