Jia Xuemei, Gao Yunxiao, Liu Liran, Guo Yuxi, Wang Jie, Ma Hongyu, Zhao Runyuan, Li Bolin, Du Yao, Yang Qian
Hebei University of Chinese Medicine, Shijiazhuang, Hebei 050091, China.
Department of Traditional Chinese Medicine, Hebei General Hospital, Shijiazhuang, Hebei 050051, China.
Evid Based Complement Alternat Med. 2022 Apr 19;2022:6211215. doi: 10.1155/2022/6211215. eCollection 2022.
This study is aimed to reveal the possible mechanisms of artemisinin in the treatment of ulcerative colitis (UC) through bioinformatics analysis and experimental verification in UC model rats.
Firstly, we searched two microarray data of the Gene Expression Omnibus (GEO) database to explore the differentially expressed genes (DEGs) between UC samples and normal samples. Then, we selected DEGs for gene ontology (GO) function enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. The acute UC model of rats was established by using 3.5% dextran sulfate sodium (DSS) for 10 days to verify the core pathway. Finally, we evaluated the therapeutic effect of artemisinin at the molecular level and used metabonomics to study the endogenous metabolites in the rat serum.
We screened in the GEO database and selected two eligible microarray datasets, GSE36807 and GSE9452. We performed GO function and KEGG pathway enrichment analyses of DEGs and found that these DEGs were mainly enriched in the inflammatory response, immune response, and IL-17 and NF-B signaling pathways. Finally, we verified the IL-17 signaling pathway and key cytokines, and ELISA and immunohistochemical results showed that artemisinin could downregulate the expression of proinflammatory cytokines such as IL-1 and IL-17 in the IL-17 signaling pathway and upregulate the expression of the anti-inflammatory cytokine PPAR-. Metabolomics analysis showed that 33 differential metabolites were identified in the artemisinin group (AG) compared to the model group (MG). Differential metabolites were mainly involved in alanine, aspartate, and glutamate metabolism and synthesis and degradation of ketone bodies.
In this study, we found that artemisinin can significantly inhibit the inflammatory response in UC rats and regulate metabolites and related metabolic pathways. This study provides a foundation for further research on the mechanism of artemisinin in the treatment of UC.
本研究旨在通过生物信息学分析及对溃疡性结肠炎（UC）模型大鼠的实验验证，揭示青蒿素治疗UC的可能机制。
首先，检索基因表达综合数据库（GEO）中的两个微阵列数据，以探索UC样本与正常样本之间的差异表达基因（DEGs）。然后，选择DEGs进行基因本体（GO）功能富集分析和京都基因与基因组百科全书（KEGG）通路富集分析。使用3.5%硫酸葡聚糖钠（DSS）建立大鼠急性UC模型10天以验证核心通路。最后，在分子水平评估青蒿素的治疗效果，并采用代谢组学研究大鼠血清中的内源性代谢物。
我们在GEO数据库中筛选并选择了两个符合条件的微阵列数据集GSE36807和GSE9452。对DEGs进行了GO功能和KEGG通路富集分析，发现这些DEGs主要富集于炎症反应、免疫反应以及IL-17和NF-κB信号通路。最后，我们验证了IL-17信号通路和关键细胞因子，酶联免疫吸附测定（ELISA）和免疫组化结果表明，青蒿素可下调IL-17信号通路中促炎细胞因子如IL-1和IL-17的表达，并上调抗炎细胞因子过氧化物酶体增殖物激活受体（PPAR）-γ的表达。代谢组学分析表明，与模型组（MG）相比，青蒿素组（AG）鉴定出33种差异代谢物。差异代谢物主要参与丙氨酸、天冬氨酸和谷氨酸代谢以及酮体的合成与降解。
在本研究中，我们发现青蒿素可显著抑制UC大鼠的炎症反应，并调节代谢物及相关代谢通路。本研究为进一步研究青蒿素治疗UC的机制提供了基础。
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