Astragaloside II pretreatment alleviates PM2.5-induced lung injury in mice via MAPK/Nrf2/GPX4 axis-mediated suppression of ferroptosis
Exposure to fine particulate matter (PM2.5) induces inflammation and oxidative stress, contributing to respiratory diseases, including lung injury. Astragaloside II (AS II), a natural product derived from Astragali Radix (AR), demonstrates dual anti-inflammatory and antioxidant activities. This work...
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| Language: | English |
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Elsevier
2025-09-01
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| Series: | Ecotoxicology and Environmental Safety |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0147651325009583 |
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| author | Liyun Liu Zherui Shen Nan Jia Qian Chen Chen Chen Yi Luo Xuemei Dai Sijing Zhao Caixia Pei Demei Huang Yilan Wang Tao Shen Zhenxing Wang |
| author_facet | Liyun Liu Zherui Shen Nan Jia Qian Chen Chen Chen Yi Luo Xuemei Dai Sijing Zhao Caixia Pei Demei Huang Yilan Wang Tao Shen Zhenxing Wang |
| author_sort | Liyun Liu |
| collection | DOAJ |
| description | Exposure to fine particulate matter (PM2.5) induces inflammation and oxidative stress, contributing to respiratory diseases, including lung injury. Astragaloside II (AS II), a natural product derived from Astragali Radix (AR), demonstrates dual anti-inflammatory and antioxidant activities. This work systematically evaluates AS II's prophylactic efficacy and molecular pathways in mitigating PM2.5-triggered pulmonary damage using a murine model. Intratracheal PM2.5 suspension (7.5 mg/kg) was applied, with AS II (25 and 50 mg/kg) pretreated via intraperitoneal (i.p.) injection before the pollutant challenge. Results demonstrated that AS II alleviated PM2.5-induced lung injury, mitigated pulmonary edema and inflammation, and reduced levels of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β). AS II upregulated glutathione (GSH) and catalase (CAT) levels while downregulating reactive oxygen species (ROS) and malondialdehyde (MDA). Mechanistically, AS II inhibited the mitogen-activated protein kinase (MAPK) signalling pathway, activated nuclear factor erythroid 2-related factor 2 (Nrf2), enhanced expression of glutathione peroxidase 4 (GPX4), and elevated other antioxidant proteins while suppressing ferroptosis and oxidative stress markers. To further validate the role of ferroptosis, RSL3—a small-molecule ferroptosis agonist that binds and inactivates GPX4—was employed. The protective efficacy of AS II against lung injury was effectively counteracted by RSL3-induced GPX4 inactivation. Collectively, AS II protects against PM2.5-induced pulmonary injury by modulating the MAPK/NRF2/GPX4 signaling axis to inhibit ferroptosis, thereby providing a novel therapeutic strategy for the treatment of PM2.5-associated pulmonary diseases. |
| format | Article |
| id | doaj-art-31b2eb413bf245eea83b119b2cef6a42 |
| institution | DOAJ |
| issn | 0147-6513 |
| language | English |
| publishDate | 2025-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Ecotoxicology and Environmental Safety |
| spelling | doaj-art-31b2eb413bf245eea83b119b2cef6a422025-08-20T03:03:58ZengElsevierEcotoxicology and Environmental Safety0147-65132025-09-0130211861310.1016/j.ecoenv.2025.118613Astragaloside II pretreatment alleviates PM2.5-induced lung injury in mice via MAPK/Nrf2/GPX4 axis-mediated suppression of ferroptosisLiyun Liu0Zherui Shen1Nan Jia2Qian Chen3Chen Chen4Yi Luo5Xuemei Dai6Sijing Zhao7Caixia Pei8Demei Huang9Yilan Wang10Tao Shen11Zhenxing Wang12Chengdu University of Traditional Chinese Medicine, Chengdu 611137, ChinaChengdu University of Traditional Chinese Medicine, Chengdu 611137, ChinaHospital of Chengdu University of Traditional Chinese Medicine, Chengdu 610072, ChinaHospital of Chengdu University of Traditional Chinese Medicine, Chengdu 610072, ChinaHospital of Chengdu University of Traditional Chinese Medicine, Chengdu 610072, ChinaHospital of Chengdu University of Traditional Chinese Medicine, Chengdu 610072, ChinaHospital of Chengdu University of Traditional Chinese Medicine, Chengdu 610072, ChinaSchool of Traditional Chinese Medicine, Chongqing Medical and Pharmaceutical College, Chongqing 401331, ChinaHospital of Chengdu University of Traditional Chinese Medicine, Chengdu 610072, ChinaHospital of Chengdu University of Traditional Chinese Medicine, Chengdu 610072, ChinaHospital of Chengdu University of Traditional Chinese Medicine, Chengdu 610072, China; Corresponding authors.Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China; Corresponding authors.Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu 610072, China; Corresponding authors.Exposure to fine particulate matter (PM2.5) induces inflammation and oxidative stress, contributing to respiratory diseases, including lung injury. Astragaloside II (AS II), a natural product derived from Astragali Radix (AR), demonstrates dual anti-inflammatory and antioxidant activities. This work systematically evaluates AS II's prophylactic efficacy and molecular pathways in mitigating PM2.5-triggered pulmonary damage using a murine model. Intratracheal PM2.5 suspension (7.5 mg/kg) was applied, with AS II (25 and 50 mg/kg) pretreated via intraperitoneal (i.p.) injection before the pollutant challenge. Results demonstrated that AS II alleviated PM2.5-induced lung injury, mitigated pulmonary edema and inflammation, and reduced levels of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β). AS II upregulated glutathione (GSH) and catalase (CAT) levels while downregulating reactive oxygen species (ROS) and malondialdehyde (MDA). Mechanistically, AS II inhibited the mitogen-activated protein kinase (MAPK) signalling pathway, activated nuclear factor erythroid 2-related factor 2 (Nrf2), enhanced expression of glutathione peroxidase 4 (GPX4), and elevated other antioxidant proteins while suppressing ferroptosis and oxidative stress markers. To further validate the role of ferroptosis, RSL3—a small-molecule ferroptosis agonist that binds and inactivates GPX4—was employed. The protective efficacy of AS II against lung injury was effectively counteracted by RSL3-induced GPX4 inactivation. Collectively, AS II protects against PM2.5-induced pulmonary injury by modulating the MAPK/NRF2/GPX4 signaling axis to inhibit ferroptosis, thereby providing a novel therapeutic strategy for the treatment of PM2.5-associated pulmonary diseases.http://www.sciencedirect.com/science/article/pii/S0147651325009583PM2.5Lung injuryAstragaloside IIMAPK/Nrf2/GPX4Ferroptosis |
| spellingShingle | Liyun Liu Zherui Shen Nan Jia Qian Chen Chen Chen Yi Luo Xuemei Dai Sijing Zhao Caixia Pei Demei Huang Yilan Wang Tao Shen Zhenxing Wang Astragaloside II pretreatment alleviates PM2.5-induced lung injury in mice via MAPK/Nrf2/GPX4 axis-mediated suppression of ferroptosis Ecotoxicology and Environmental Safety PM2.5 Lung injury Astragaloside II MAPK/Nrf2/GPX4 Ferroptosis |
| title | Astragaloside II pretreatment alleviates PM2.5-induced lung injury in mice via MAPK/Nrf2/GPX4 axis-mediated suppression of ferroptosis |
| title_full | Astragaloside II pretreatment alleviates PM2.5-induced lung injury in mice via MAPK/Nrf2/GPX4 axis-mediated suppression of ferroptosis |
| title_fullStr | Astragaloside II pretreatment alleviates PM2.5-induced lung injury in mice via MAPK/Nrf2/GPX4 axis-mediated suppression of ferroptosis |
| title_full_unstemmed | Astragaloside II pretreatment alleviates PM2.5-induced lung injury in mice via MAPK/Nrf2/GPX4 axis-mediated suppression of ferroptosis |
| title_short | Astragaloside II pretreatment alleviates PM2.5-induced lung injury in mice via MAPK/Nrf2/GPX4 axis-mediated suppression of ferroptosis |
| title_sort | astragaloside ii pretreatment alleviates pm2 5 induced lung injury in mice via mapk nrf2 gpx4 axis mediated suppression of ferroptosis |
| topic | PM2.5 Lung injury Astragaloside II MAPK/Nrf2/GPX4 Ferroptosis |
| url | http://www.sciencedirect.com/science/article/pii/S0147651325009583 |
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