Phillyrin attenuates TGF-β1-induced pulmonary fibrosis by modulating the Nrf2/HO-1 pathway and epithelial-mesenchymal transition

IF 3 3区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Molecular immunology Pub Date : 2026-05-01 Epub Date: 2026-03-10 DOI:10.1016/j.molimm.2026.03.003

Jinjin Yu , Yang Liu , Huixin Song , Lingyi Liu , Lingli Li , Yuzhi Luo , Yajing Ma , Ruisi Zhu , Xinyao Liu , Songyuan Xia , Dezhu Zhang , Jianguo Meng , Weifeng Li , Xiaofeng Niu

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引用次数: 0

Abstract

Background

Phillyrin (Phi), a natural lignan glycoside derived from Fructus Forsythiae, has been reported to exhibit anti-inflammatory and antioxidant activities. In this study, we investigated its therapeutic potential in a TGF-β1-induced model of epithelial-mesenchymal transition (EMT) in A549 human alveolar epithelial cells.

Methods

The mechanisms of Phi were initially predicted using network pharmacology and molecular docking. Subsequently, A549 cells were stimulated with TGF-β1 and treated with Phi. Key assessments included cell viability, inflammatory and oxidative stress markers, EMT-related proteins (E-cadherin, α-SMA, vimentin), and fibrosis-associated molecules (collagen I, fibronectin, MMP-2). The activation of the Nrf2/HO-1 antioxidant pathway was also examined.

Results

Phi significantly attenuated TGF-β1-induced EMT and fibrotic responses in A549 cells. It not only suppressed inflammatory cytokine production and oxidative stress but also restored epithelial marker expression and reduced mesenchymal and fibrotic protein levels. Moreover, Phi upregulated the Nrf2/HO-1 signaling pathway, enhancing cellular antioxidant capacity.

Conclusion

These findings suggest that Phi possesses potent anti-inflammatory, antioxidant, and anti-fibrotic properties, effectively inhibiting TGF-β1-driven EMT in alveolar epithelial cells. Phi may represent a promising therapeutic candidate for treating idiopathic pulmonary fibrosis and other fibrotic lung diseases.

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philyrin通过调节Nrf2/HO-1通路和上皮-间质转化，减轻TGF-β1诱导的肺纤维化

连翘苷（phillyrin, Phi）是一种从连翘属植物中提取的天然木脂素苷，具有抗炎和抗氧化活性。在本研究中，我们在TGF-β1诱导的A549人肺泡上皮细胞上皮-间质转化（EMT）模型中研究了其治疗潜力。方法利用网络药理学和分子对接技术对Phi的作用机制进行初步预测。随后，用TGF-β1刺激A549细胞，并用Phi处理。关键评估包括细胞活力、炎症和氧化应激标志物、emt相关蛋白（E-cadherin、α-SMA、vimentin）和纤维化相关分子（胶原蛋白I、纤维连接蛋白、MMP-2）。研究了Nrf2/HO-1抗氧化途径的激活情况。结果sphi能明显减弱TGF-β1诱导的A549细胞EMT和纤维化反应。它不仅能抑制炎症细胞因子的产生和氧化应激，还能恢复上皮标志物的表达，降低间充质和纤维化蛋白的水平。此外，Phi上调Nrf2/HO-1信号通路，增强细胞抗氧化能力。结论Phi具有较强的抗炎、抗氧化和抗纤维化作用，可有效抑制TGF-β1驱动的肺泡上皮细胞EMT。Phi可能是治疗特发性肺纤维化和其他纤维化肺部疾病的有希望的治疗候选药物。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Molecular immunology 医学-免疫学

CiteScore

6.90

自引率

2.80%

发文量

324

审稿时长

50 days

期刊介绍： Molecular Immunology publishes original articles, reviews and commentaries on all areas of immunology, with a particular focus on description of cellular, biochemical or genetic mechanisms underlying immunological phenomena. Studies on all model organisms, from invertebrates to humans, are suitable. Examples include, but are not restricted to: Infection, autoimmunity, transplantation, immunodeficiencies, inflammation and tumor immunology Mechanisms of induction, regulation and termination of innate and adaptive immunity Intercellular communication, cooperation and regulation Intracellular mechanisms of immunity (endocytosis, protein trafficking, pathogen recognition, antigen presentation, etc) Mechanisms of action of the cells and molecules of the immune system Structural analysis Development of the immune system Comparative immunology and evolution of the immune system "Omics" studies and bioinformatics Vaccines, biotechnology and therapeutic manipulation of the immune system (therapeutic antibodies, cytokines, cellular therapies, etc) Technical developments.