Li Xiang, Jiang Sishi, Li Haili, Li Shilin, Hu Yingchun
Department of Emergency Medicine, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, China.
PLoS One. 2025 Sep 8;20(9):e0331401. doi: 10.1371/journal.pone.0331401. eCollection 2025.
Heat illness is a dangerous condition marked by a widespread inflammatory response. Although Pogostemon cablin (Blanco) Benth and its derivatives are clinically used, their mechanisms remain unclear.
11 heat illness patients and 14 healthy volunteers from Southwest Medical University Affiliated Hospital were enrolled. Bulk RNA sequencing of peripheral blood samples identified disease-relevant modules via weighted gene co-expression network analysis (WGCNA). Active ingredients and targets of P. cablin were retrieved from TCMSP. GO/KEGG, protein-protein interaction (PPI), and ROC analyses were performed. Core genes were localized through single-cell RNA sequencing, with compound-target interactions validated by molecular docking.
Enrichment analysis revealed nine cross-targets in TNF/NF-κB pathways. Core targets (NFKBIA, PARP1) showed high diagnostic sensitivity/specificity. Single-cell data indicated predominant expression in monocytes and CD1C-CD141 dendritic cells. Molecular docking demonstrated strong affinity of quercetin/quercimeritrin for NFKBIA/PARP1/LACTB, with molecular dynamics confirming structural stability of complexes (RMSD < 2Å after 100 ns).
This pioneering study integrates network pharmacology and molecular simulations to elucidate P. cablin's therapeutic targets for heat illness, providing a foundation for advanced therapies.
热射病是一种以广泛炎症反应为特征的危险病症。虽然广藿香及其衍生物在临床上有应用，但其作用机制尚不清楚。
招募了来自西南医科大学附属医院的11例热射病患者和14名健康志愿者。通过加权基因共表达网络分析（WGCNA）对外周血样本进行批量RNA测序，以识别与疾病相关的模块。从中药系统药理学数据库与分析平台（TCMSP）中检索广藿香的活性成分和靶点。进行基因本体论（GO）/京都基因与基因组百科全书（KEGG）、蛋白质-蛋白质相互作用（PPI）和受试者工作特征曲线（ROC）分析。通过单细胞RNA测序对核心基因进行定位，通过分子对接验证化合物-靶点相互作用。
富集分析揭示了肿瘤坏死因子（TNF）/核因子κB（NF-κB）通路中的9个交叉靶点。核心靶点（NFKBIA、PARP1）显示出较高的诊断敏感性/特异性。单细胞数据表明在单核细胞和CD1C-CD141树突状细胞中主要表达。分子对接表明槲皮素/槲皮苷对NFKBIA/PARP1/LACTB具有很强的亲和力，分子动力学证实复合物的结构稳定性（100纳秒后均方根偏差<2埃）。
这项开创性研究整合了网络药理学和分子模拟，以阐明广藿香治疗热射病的靶点，为进一步的治疗提供了基础。
