Graduate School, Beijing University of Chinese Medicine, Beijing, China.
Traditional Chinese Medicine Department of Rheumatism, China-Japan Friendship Hospital, Beijing, China.
BMC Immunol. 2024 Feb 12;25(1):16. doi: 10.1186/s12865-024-00605-3.
The study aimed to explore the mechanism of artemisinin in treating primary Sjögren's syndrome (pSS) based on network pharmacology and experimental validation.
Relevant targets of the artemisinin and pSS-related targets were integrated by public databases online. An artemisinin-pSS network was constructed by Cytoscape. The genes of artemisinin regulating pSS were imported into STRING database to construct a protein-protein interaction (PPI) network in order to predict the key targets. The enrichment analyses were performed to predict the crucial mechanism and pathway of artemisinin against pSS. The active component of artemisinin underwent molecular docking with the key proteins. Artemisinin was administered intragastrically to SS-like NOD/Ltj mice to validate the efficacy and critical mechanisms.
Network Pharmacology analysis revealed that artemisinin corresponded to 412 targets, and pSS related to 1495 genes. There were 40 intersection genes between artemisinin and pSS. KEGG indicated that therapeutic effects of artemisinin on pSS involves IL-17 signaling pathway, HIF-1 signaling pathway, apoptosis signaling pathway, Th17 cell differentiation, PI3K-Akt signaling pathway, and MAPK signaling pathway. Molecular docking results further showed that the artemisinin molecule had higher binding energy by combining with the key nodes in IL-17 signaling pathway. In vivo experiments suggested artemisinin can restored salivary gland secretory function and improve the level of glandular damage of NOD/Ltj mice. It contributed to the increase of regulatory T cells (Tregs) and the downregulated secretion of IL-17 in NOD/Ltj model.
The treatment of pSS with artemisinin is closely related to modulating the balance of Tregs and Th17 cells via T cell differentiation.
本研究旨在基于网络药理学和实验验证探讨青蒿素治疗原发性干燥综合征（pSS）的作用机制。
通过在线公共数据库整合青蒿素相关靶点和 pSS 相关靶点，利用 Cytoscape 构建青蒿素-pSS 网络图，将青蒿素调控 pSS 的基因导入 STRING 数据库构建蛋白-蛋白相互作用（PPI）网络，预测关键靶点，进行富集分析，预测青蒿素治疗 pSS 的关键机制和通路。对青蒿素的活性成分进行分子对接，与关键蛋白结合。将青蒿素灌胃给药于 SS 样 NOD/Ltj 小鼠，验证疗效和关键机制。
网络药理学分析表明，青蒿素对应 412 个靶点，pSS 相关 1495 个基因，青蒿素与 pSS 有 40 个交集基因。KEGG 表明青蒿素治疗 pSS 的疗效涉及 IL-17 信号通路、HIF-1 信号通路、细胞凋亡信号通路、Th17 细胞分化、PI3K-Akt 信号通路和 MAPK 信号通路。分子对接结果进一步表明，青蒿素分子与 IL-17 信号通路中的关键节点结合具有更高的结合能。体内实验表明，青蒿素可恢复唾液腺分泌功能，改善 NOD/Ltj 小鼠的腺体损伤程度。它有助于增加调节性 T 细胞（Tregs）并下调 NOD/Ltj 模型中 IL-17 的分泌。
青蒿素治疗 pSS 与调节 T 细胞分化过程中的 Tregs 和 Th17 细胞平衡密切相关。
