Hu Weisheng, Wang Yinlan, Zhou Yingjie, Shi Junbao, Li Zengyan, Jiang Xiaoling, Wu Qinyuan, Zhong Changming, Weng Huilan, Ouyang Sijie, Jing Yuan, Cai Xianxiang, Ye Mingda, Huang Ning
The Second Affiliated Hospital of Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian, 350001, China.
Fujian Provincial Key Laboratory for Integrated Traditional Chinese and Western Medicine Dermatology, The Second Affiliated Hospital of Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian, 350001, China.
Heliyon. 2025 Jan 10;11(2):e41707. doi: 10.1016/j.heliyon.2025.e41707. eCollection 2025 Jan 30.
This study aimed to explore the molecular mechanisms of Lithospermum erythrorhizon oil in treating atopic dermatitis (AD), with a particular focus on its regulatory effect on the PI3K-Akt signaling pathway.
Utilizing a network pharmacology approach integrated with experimental validation, we identified active components and potential targets of Lithospermum erythrorhizon oil via TCMSP, ChemSrc, PubChem, and PharmMapper. Common targets were selected by intersecting these with AD-related targets from GeneCards. A protein-protein interaction (PPI) network was built using STRING, and functional analysis Gene Ontology (GO) and pathway enrichment Kyoto Encyclopedia of Genes and Genomes (KEGG) were performed on Metascape. A Gene-miRNA regulatory network was constructed on miRTarBase and NetworkAnalyst, with miRNA functions annotated by miEAA. An AD mouse model induced by DNCB was established to evaluate Lithospermum erythrorhizon oil's therapeutic efficacy, its influence on inflammatory markers, and the PI3K-Akt pathway.
Fifteen common targets were found to be crucial in AD pathogenesis. The PPI network, constructed using STRING, revealed interactions among 13 nodes and 42 edges, with Cytoscape analysis highlighting 10 core targets. GO and KEGG analyses were significant in biological processes like cell migration and inflammatory response regulation, and in pathways such as IL-17 signaling and PI3K-Akt signaling. The Gene-miRNA network suggested Lithospermum erythrorhizon oil may regulate miRNAs like hsa-mir-124-3p and hsa-let-7b-5p. Experimental results showed that Lithospermum erythrorhizon oil significantly improved AD symptoms in mice, reduced IL-4 and IL-13 levels, and decreased p-PI3K, p-PI3K/PI3K, p-Akt, and p-Akt/Akt expression, inhibiting PI3K-Akt pathway activation.
Lithospermum erythrorhizon oil exerts multi-target, multi-pathway therapeutic effects in AD, potentially through suppressing Th2-mediated immune responses and the PI3K-Akt signaling pathway, suggesting novel avenues for AD treatment strategies.
本研究旨在探讨紫草油治疗特应性皮炎（AD）的分子机制，特别关注其对PI3K-Akt信号通路的调节作用。
采用网络药理学方法并结合实验验证，我们通过中药系统药理学数据库与分析平台（TCMSP）、化学资源数据库（ChemSrc）、公共化学数据库（PubChem）和药物靶点预测平台（PharmMapper）确定了紫草油的活性成分和潜在靶点。通过将这些靶点与来自基因卡片（GeneCards）的AD相关靶点进行交叉比对来选择共同靶点。使用STRING构建蛋白质-蛋白质相互作用（PPI）网络，并在Metascape上对基因本体论（GO）进行功能分析以及对京都基因与基因组百科全书（KEGG）进行通路富集分析。在miRTarBase和NetworkAnalyst上构建基因- miRNA调控网络，并用miEAA注释miRNA功能。建立二硝基氯苯（DNCB）诱导的AD小鼠模型，以评估紫草油的治疗效果、其对炎症标志物的影响以及对PI3K-Akt通路的影响。
发现15个共同靶点在AD发病机制中起关键作用。使用STRING构建的PPI网络显示13个节点和42条边之间存在相互作用，Cytoscape分析突出了10个核心靶点。GO和KEGG分析在细胞迁移和炎症反应调节等生物学过程以及白细胞介素-17信号传导和PI3K-Akt信号传导等通路中具有显著意义。基因- miRNA网络表明紫草油可能调节如hsa-mir-124-3p和hsa-let-7b-5p等miRNA。实验结果表明，紫草油显著改善了小鼠的AD症状，降低了白细胞介素-4和白细胞介素-13水平，并降低了磷酸化PI3K（p-PI3K）、p-PI3K/PI3K、磷酸化Akt（p-Akt）和p-Akt/Akt的表达，抑制了PI3K-Akt通路的激活。
紫草油在AD中发挥多靶点、多途径的治疗作用，可能是通过抑制Th2介导的免疫反应和PI3K-Akt信号通路，为AD治疗策略提供了新途径。
Zotero 插件
