Liu Kai, Zeng Hui, Zhu Xiao, Deng Hao, Deng Wei, Li Sixin, Zhu Yaxian, Bin Ji, Lu Shuai, Wu Wenke, Wu Qi, Liao Jun, Hu Ge, Chang Wei, Ying Yekui, Wang Ying, Zhu Zhenhua
Department of Otorhinolaryngology-Head and Neck Surgery, The First Hospital of Hunan University of Chinese Medicine, Changsha 410007, China; Experiment Center of Medical Innovation, The First Hospital of Hunan University of Chinese Medicine, Changsha 410007, China.
Department of Otorhinolaryngology-Head and Neck Surgery, The First Hospital of Hunan University of Chinese Medicine, Changsha 410007, China.
Phytomedicine. 2025 Sep;145:157065. doi: 10.1016/j.phymed.2025.157065. Epub 2025 Jul 11.
Chronic rhinosinusitis (CRS), a prevalent upper respiratory inflammatory disorder, remains challenging in clinical management due to the high recurrence rates. Traditional Chinese Medicine (TCM) pathogenesis theory posits that CRS primarily stems from deficiency syndromes involving pulmonary and splenic dysfunction. Shenling Tongqiao Powder (SLTQP), a formulated herbal preparation, has demonstrated clinical efficacy in enhancing pulmonary-splenic function and CRS symptom alleviation. But its underlying pharmacological mechanisms require systematic elucidation.
Nasal mucosa of nasal septum deviation and CRS without nasal polyp (CRSsNP) patients were collected for histopathological analysis in epithelial-mesenchymal transition (EMT). The rat model of CRS was established using Staphylococcus aureus while the body weight, the number of nose-scratching and sneezing were recorded. Sinus inflammation was evaluated by computed tomography (CT) scanning. Histopathological staining, Reverse Transcription Quantitative Real-Time Polymerase Chain Reaction (RT-qPCR) and western blot were applied for assessment of TGF-β1/Smad and Wnt/β-catenin signaling and EMT in rat and cell model. Inflammatory factors of rat nasal lavage solution and serum were analyzed by ELISA. LC-MS/MS was used for analysis of SLTQP decoction and pharmaceutic serum. The energy between these molecules and TGF-β1/Smad and Wnt/β-catenin was calculated by molecular docking, the direct binding affinity was confirmed and quantified via surface plasmon resonance (SPR).
Histopathological analysis revealed marked EMT elevation in nasal mucosa specimens from CRSsNP patients. SLTQP administration significantly attenuated EMT progression and suppressed nasal inflammatory responses in CRS rat models, likely mediated via concurrent inhibition of TGF-β1/Smad and Wnt/β-catenin signaling cascades. Phytochemical profiling via liquid chromatography-mass spectrometry (LC-MS) characterized both the native SLTQP decoction components and their bioactive metabolites in systemic circulation. Notably, molecular docking analyses predicted and SPR confirmed strong binding affinities between these identified compounds and critical regulatory nodes within TGF-β1/Smad and Wnt/β-catenin, suggesting a potential multi-target therapeutic mechanism.
Our integrated approaches firstly documented EMT dysregulation by multiple makers in CRSsNP patients, and provided novel insights into SLTQP's anti-EMT effects through dual pathway modulation, supporting its application as a complementary CRS treatment strategy.
慢性鼻-鼻窦炎（CRS）是一种常见的上呼吸道炎症性疾病，由于其高复发率，在临床治疗中仍然具有挑战性。中医发病机制理论认为，CRS主要源于涉及肺脾功能失调的虚证。参苓通窍散（SLTQP）是一种配制的草药制剂，已显示出在增强肺脾功能和缓解CRS症状方面具有临床疗效。但其潜在的药理机制需要系统阐明。
收集鼻中隔偏曲和无鼻息肉的CRS（CRSsNP）患者的鼻黏膜进行上皮-间质转化（EMT）的组织病理学分析。使用金黄色葡萄球菌建立CRS大鼠模型，记录体重、抓鼻和打喷嚏次数。通过计算机断层扫描（CT）扫描评估鼻窦炎症。应用组织病理学染色、逆转录定量实时聚合酶链反应（RT-qPCR）和蛋白质印迹法评估大鼠和细胞模型中的TGF-β1/Smad和Wnt/β-连环蛋白信号通路及EMT。通过酶联免疫吸附测定（ELISA）分析大鼠鼻灌洗液和血清中的炎症因子。采用液相色谱-串联质谱（LC-MS/MS）分析SLTQP水煎剂和含药血清。通过分子对接计算这些分子与TGF-β1/Smad和Wnt/β-连环蛋白之间的能量，通过表面等离子体共振（SPR）确认并定量直接结合亲和力。
组织病理学分析显示CRSsNP患者鼻黏膜标本中EMT明显升高。给予SLTQP可显著减轻CRS大鼠模型中的EMT进展并抑制鼻炎症反应，这可能是通过同时抑制TGF-β1/Smad和Wnt/β-连环蛋白信号级联介导的。通过液相色谱-质谱联用（LC-MS）进行的植物化学分析确定了SLTQP水煎剂的天然成分及其在体循环中的生物活性代谢产物。值得注意的是，分子对接分析预测并经SPR证实这些已鉴定的化合物与TGF-β1/Smad和Wnt/β-连环蛋白中的关键调节节点具有强结合亲和力，提示了一种潜在的多靶点治疗机制。
我们的综合方法首次记录了CRSsNP患者中多种标志物导致的EMT失调，并通过双途径调节为SLTQP的抗EMT作用提供了新见解，支持其作为CRS辅助治疗策略的应用。
