Luteolin 7-Glucuronide in <i>Artemisia rupestris</i> L. Extract Attenuates Pulmonary Fibrosis by Inhibiting Fibroblast Activation and FMT via Targeting of TGF-β1
Pulmonary fibrosis (PF) is a chronic pulmonary disease characterized by excessive extracellular matrix (ECM) deposition, with cigarette smoking being a major risk factor and no effective treatment at present. Transforming growth factor beta 1 (TGF-β1) plays a key role in PF and regulating oxidative...
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MDPI AG
2025-04-01
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| Series: | Antioxidants |
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| author | Lingfeng Peng Yimeng Fan Luyao Wang Chao Han Zhihui Hao |
| author_facet | Lingfeng Peng Yimeng Fan Luyao Wang Chao Han Zhihui Hao |
| author_sort | Lingfeng Peng |
| collection | DOAJ |
| description | Pulmonary fibrosis (PF) is a chronic pulmonary disease characterized by excessive extracellular matrix (ECM) deposition, with cigarette smoking being a major risk factor and no effective treatment at present. Transforming growth factor beta 1 (TGF-β1) plays a key role in PF and regulating oxidative stress. This study investigated the effects and mechanisms of <i>Artemisia rupestris</i> L. ethanol extract (ER) on cigarette smoke (CS)-induced PF. We used pull-down and LC–MS analyses to screen and identify compounds that bind to TGF-β1 in ER. We demonstrated that ER inhibits CS-induced PF, lung inflammation, and oxidative stress, thereby improving pulmonary structural injury. The ER inhibits fibroblast activation and fibroblast-to-myofibroblast transition (FMT), reducing collagen deposition for the treatment of PF. We identified the active ingredient in ER that binds to TGF-β1, namely, Luteolin 7-glucuronide (LG). LG inhibits the TGF-β1 signaling pathway through targeted binding to TGF-β1, downregulates the expression of downstream proteins (including collagen I, α-SMA, MMP-2, and MMP-9), and inhibits <i>fibronectin</i> expression. It also inhibits fibroblast activation and FMT, enhances <i>E-cadherin</i> expression to promote fibroblast adhesion, and suppresses collagen deposition, alleviating PF. Based on these findings, we propose that LG might be a promising therapeutic drug candidate for treating PF. |
| format | Article |
| id | doaj-art-d1628e1b3a034166abfed0ee7a425355 |
| institution | Kabale University |
| issn | 2076-3921 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | MDPI AG |
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| series | Antioxidants |
| spelling | doaj-art-d1628e1b3a034166abfed0ee7a4253552025-08-20T03:47:48ZengMDPI AGAntioxidants2076-39212025-04-0114553310.3390/antiox14050533Luteolin 7-Glucuronide in <i>Artemisia rupestris</i> L. Extract Attenuates Pulmonary Fibrosis by Inhibiting Fibroblast Activation and FMT via Targeting of TGF-β1Lingfeng Peng0Yimeng Fan1Luyao Wang2Chao Han3Zhihui Hao4Chinese Veterinary Medicine Innovation Center, College of Veterinary Medicine, China Agricultural University, Beijing 100193, ChinaChinese Veterinary Medicine Innovation Center, College of Veterinary Medicine, China Agricultural University, Beijing 100193, ChinaChinese Veterinary Medicine Innovation Center, College of Veterinary Medicine, China Agricultural University, Beijing 100193, ChinaChinese Veterinary Medicine Innovation Center, College of Veterinary Medicine, China Agricultural University, Beijing 100193, ChinaChinese Veterinary Medicine Innovation Center, College of Veterinary Medicine, China Agricultural University, Beijing 100193, ChinaPulmonary fibrosis (PF) is a chronic pulmonary disease characterized by excessive extracellular matrix (ECM) deposition, with cigarette smoking being a major risk factor and no effective treatment at present. Transforming growth factor beta 1 (TGF-β1) plays a key role in PF and regulating oxidative stress. This study investigated the effects and mechanisms of <i>Artemisia rupestris</i> L. ethanol extract (ER) on cigarette smoke (CS)-induced PF. We used pull-down and LC–MS analyses to screen and identify compounds that bind to TGF-β1 in ER. We demonstrated that ER inhibits CS-induced PF, lung inflammation, and oxidative stress, thereby improving pulmonary structural injury. The ER inhibits fibroblast activation and fibroblast-to-myofibroblast transition (FMT), reducing collagen deposition for the treatment of PF. We identified the active ingredient in ER that binds to TGF-β1, namely, Luteolin 7-glucuronide (LG). LG inhibits the TGF-β1 signaling pathway through targeted binding to TGF-β1, downregulates the expression of downstream proteins (including collagen I, α-SMA, MMP-2, and MMP-9), and inhibits <i>fibronectin</i> expression. It also inhibits fibroblast activation and FMT, enhances <i>E-cadherin</i> expression to promote fibroblast adhesion, and suppresses collagen deposition, alleviating PF. Based on these findings, we propose that LG might be a promising therapeutic drug candidate for treating PF.https://www.mdpi.com/2076-3921/14/5/533<i>Artemisia rupestris</i> L.luteolin 7-glucuronidepulmonary fibrosisTGF-β1 signaling pathway |
| spellingShingle | Lingfeng Peng Yimeng Fan Luyao Wang Chao Han Zhihui Hao Luteolin 7-Glucuronide in <i>Artemisia rupestris</i> L. Extract Attenuates Pulmonary Fibrosis by Inhibiting Fibroblast Activation and FMT via Targeting of TGF-β1 Antioxidants <i>Artemisia rupestris</i> L. luteolin 7-glucuronide pulmonary fibrosis TGF-β1 signaling pathway |
| title | Luteolin 7-Glucuronide in <i>Artemisia rupestris</i> L. Extract Attenuates Pulmonary Fibrosis by Inhibiting Fibroblast Activation and FMT via Targeting of TGF-β1 |
| title_full | Luteolin 7-Glucuronide in <i>Artemisia rupestris</i> L. Extract Attenuates Pulmonary Fibrosis by Inhibiting Fibroblast Activation and FMT via Targeting of TGF-β1 |
| title_fullStr | Luteolin 7-Glucuronide in <i>Artemisia rupestris</i> L. Extract Attenuates Pulmonary Fibrosis by Inhibiting Fibroblast Activation and FMT via Targeting of TGF-β1 |
| title_full_unstemmed | Luteolin 7-Glucuronide in <i>Artemisia rupestris</i> L. Extract Attenuates Pulmonary Fibrosis by Inhibiting Fibroblast Activation and FMT via Targeting of TGF-β1 |
| title_short | Luteolin 7-Glucuronide in <i>Artemisia rupestris</i> L. Extract Attenuates Pulmonary Fibrosis by Inhibiting Fibroblast Activation and FMT via Targeting of TGF-β1 |
| title_sort | luteolin 7 glucuronide in i artemisia rupestris i l extract attenuates pulmonary fibrosis by inhibiting fibroblast activation and fmt via targeting of tgf β1 |
| topic | <i>Artemisia rupestris</i> L. luteolin 7-glucuronide pulmonary fibrosis TGF-β1 signaling pathway |
| url | https://www.mdpi.com/2076-3921/14/5/533 |
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