天然AhR配体：病毒感染中动态免疫调节的新方法
Natural AhR ligands: A novel approach to dynamic immune regulation in viral infections.
摘要(中文译文)
板蓝根对呼吸道合胞病毒（RSV）有效，但其免疫调节机制尚不清楚。为阐明板蓝根活性成分抗RSV的免疫相关靶点及机制，采用LC-MS和HPLC鉴定板蓝根的化学成分及其血清中的吸收成分。基于这些血清成分，通过网络药理学预测潜在靶点，并通过分子对接、表面等离子共振（SPR）、PCR、Western blotting、免疫荧光和免疫共沉淀（co-IP）进行验证。建立鼻内RSV感染模型，评估活性成分的动态免疫调节作用。板蓝根总生物碱（IRA）主要为吲哚类生物碱。血清中鉴定出6种原型成分和5种代谢物。网络药理学、分子对接和SPR一致表明芳香烃受体（AhR）为核心靶点。机制研究证实，包括靛红在内的IRA成分可部分激活AhR。在RSV感染模型中，IRA与内源性配体犬尿氨酸协同动态调控AhR。这显著降低了病毒载量，减轻了肺损伤，并逆转了RSV诱导的过度免疫细胞浸润和细胞因子失衡。使用模拟天然成分比例的配方复现了治疗效果。本研究首次证明AhR是IRA抗RSV动态治疗效果的关键介质。IRA并非发挥孤立的抗病毒或抗炎作用，而是通过靶向AhR重编程免疫功能。这一新机制为中药的动态治疗作用提供了新视角。
Abstract
Isatidis Radix is effective against respiratory syncytial virus (RSV), yet its immune-regulatory mechanisms remain unclear. To elucidate the immune-related targets and mechanisms of the active components of Isatidis Radix against RSV. LC-MS and HPLC were used to identify the chemical profile of Isatidis Radix and its absorbed constituents in serum. Based on these serum components, network pharmacology predicted potential targets, which were validated by molecular docking, surface plasmon resonance (SPR), PCR, Western blotting, immunofluorescence, and co-immunoprecipitation (co-IP). An intranasal RSV infection model was established to assess the dynamic immunomodulatory effects of the active components. The total alkaloids from Isatidis Radix (IRA) were primarily indole alkaloids. Six prototype components and five metabolites were identified in serum. Network pharmacology, docking, and SPR consistently indicated the aryl hydrocarbon receptor (AhR) as a core target. Mechanistic studies confirmed that IRA components, including isatin, partially activated AhR. In the RSV-infected model, IRA dynamically regulated AhR in coordination with the endogenous ligand kynurenine. This significantly reduced viral load, alleviated lung injury, and reversed the excessive immune cell infiltration and cytokine imbalance induced by RSV. The therapeutic effects were replicated using a formulation mimicking the natural component ratio. This study is the first to demonstrate that AhR is a key mediator of IRA's dynamic therapeutic effects against RSV. Rather than exerting isolated antiviral or anti-inflammatory actions, IRA reprograms immune function by targeting AhR. This novel mechanism offers a new perspective on the dynamic therapeutic actions of traditional Chinese medicine.
如何引用
AMA
Xianbang Hou, Li Chen, Yujie Huang, Ran Chen, Didi Hu, Yingji Xu, et al. Natural AhR ligands: A novel approach to dynamic immune regulation in viral infections.. Phytomedicine : international journal of phytotherapy and phytopharmacology. 2026; doi:10.1016/j.phymed.2026.158312.
APA
Xianbang Hou, Li Chen, Yujie Huang, Ran Chen, Didi Hu, Yingji Xu, et al (2026). Natural AhR ligands: A novel approach to dynamic immune regulation in viral infections.. Phytomedicine : international journal of phytotherapy and phytopharmacology. https://doi.org/10.1016/j.phymed.2026.158312
GB/T 7714
Xianbang Hou, Li Chen, Yujie Huang, Ran Chen, Didi Hu, Yingji Xu, et al. Natural AhR ligands: A novel approach to dynamic immune regulation in viral infections.[J]. Phytomedicine : international journal of phytotherapy and phytopharmacology, 2026 doi:10.1016/j.phymed.2026.158312.
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