脏四味通过抑制 TGF-β/SMAD 通路预防颗粒物诱导的肺炎症和纤维化。
Zangsiwei prevents particulate matter-induced lung inflammation and fibrosis by inhibiting the TGF-β/SMAD pathway.
机构信息
Department of Pulmonary and Critical Care Medicine, The Second Xiangya Hospital, Central South University, Changsha, Hunan, 410011, China; Hunan Centre for Evidence-based Medicine, Changsha, 410011, China; Research Unit of Respiratory Disease, Central South University, Changsha, Hunan, 410011, China; Clinical Medical Research Center for Pulmonary and Critical Care Medicine in Hunan Province, 410011, China; Diagnosis and Treatment Center of Respiratory Disease in Hunan Province, Changsha, Hunan, 410011, China.
Department of Pulmonary and Critical Care Medicine, The Second Xiangya Hospital, Central South University, Changsha, Hunan, 410011, China; Hunan Centre for Evidence-based Medicine, Changsha, 410011, China; Research Unit of Respiratory Disease, Central South University, Changsha, Hunan, 410011, China; Clinical Medical Research Center for Pulmonary and Critical Care Medicine in Hunan Province, 410011, China; Diagnosis and Treatment Center of Respiratory Disease in Hunan Province, Changsha, Hunan, 410011, China.
出版信息
J Ethnopharmacol. 2025 Jan 30;337(Pt 1):118752. doi: 10.1016/j.jep.2024.118752. Epub 2024 Sep 2.
ETHNOPHARMACOLOGICAL RELEVANCE
Zangsiwei(ZSW) is a traditional Tibetan medicine from China consisting of extracts of Rhododendron anthopogonoides Maxim, Gentiana Tourn, Corydalis hendersonii Hemsl and Berberis kansuensis C.K.Schneid. Traditionally, ZSW has been used by Tibetan physicians to treat chronic respiratory diseases. The role of ZSW in particulate matter-induced lung inflammation and fibrosis remains unclear.
AIM OF THE STUDY
Combining non-targeted metabolomics, network pharmacology, and molecular docking to explore the mechanism of ZSW in the treatment of particulate matter-induced lung inflammation and fibrosis, and validated by in vivo and in vitro experiments.
MATERIALS AND METHODS
The serum metabolite profile post-ZSW administration was first identified utilizing non-targeted metabolomics. Network pharmacology and molecular docking were employed to predict potential bioactive components and their corresponding targets. The in silico predictions were subsequently validated through in vivo studies in mice exposed to PM2.5 and silica dust, as well as in vitro studies utilizing human lung epithelial cells (A549) and lung fibroblasts (MRC5).
RESULTS
Metabolomic analysis identified specific serum metabolites that were associated with ZSW treatment. Network pharmacology and molecular docking identified key targets involved in the Transforming growth factor-β (TGF-β)/SMAD pathway, which were subsequently validated through in vivo experiments demonstrating a reduction in lung inflammation and fibrosis in ZSW-treated mice. In vitro studies demonstrated that ZSW exerts protective effects against PM2.5-induced cytotoxicity and modulates fibrotic markers in a dose-dependent manner. This is consistent with the inhibition of the TGF-β/SMAD pathway.
CONCLUSION
Our integrated approach, which combines non-targeted metabolomics, network pharmacology, and molecular docking, followed by rigorous in vivo and in vitro validation, establishes ZSW as a potential therapeutic agent for particulate matter-induced lung inflammation and fibrosis.
藏药獐牙菜（ZSW）是一种传统的藏药，由短梗獐牙菜、唐古特秦艽、藏菖蒲和藏黄连的提取物组成。传统上，藏医使用 ZSW 治疗慢性呼吸道疾病。ZSW 对颗粒物引起的肺部炎症和纤维化的作用尚不清楚。
本研究旨在结合非靶向代谢组学、网络药理学和分子对接技术，探讨 ZSW 治疗颗粒物引起的肺部炎症和纤维化的作用机制，并通过体内和体外实验进行验证。
首先，我们利用非靶向代谢组学方法鉴定了 ZSW 给药后血清代谢谱。然后，我们利用网络药理学和分子对接技术预测了潜在的生物活性成分及其相应的靶点。接着，我们通过体内实验验证了这些预测结果，实验中使用了 PM2.5 和二氧化硅粉尘暴露的小鼠模型，以及体外实验验证了这些预测结果，实验中使用了人肺上皮细胞（A549）和肺成纤维细胞（MRC5）。
代谢组学分析鉴定了与 ZSW 治疗相关的特定血清代谢物。网络药理学和分子对接技术鉴定了涉及转化生长因子-β（TGF-β）/SMAD 途径的关键靶点，这些靶点随后通过体内实验得到了验证，实验结果表明 ZSW 治疗可减轻 PM2.5 诱导的肺部炎症和纤维化。体外实验表明，ZSW 对 PM2.5 诱导的细胞毒性具有保护作用，并呈剂量依赖性调节纤维化标志物，这与 TGF-β/SMAD 途径的抑制一致。
综上所述，我们的研究结果表明，我们的综合方法，包括非靶向代谢组学、网络药理学和分子对接，以及严格的体内和体外验证，确立了 ZSW 作为一种治疗颗粒物引起的肺部炎症和纤维化的潜在治疗药物。
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