Anisodamine ameliorates crystalline silica-exposed pulmonary inflammation and fibrosis via the α7nAChR/JAK2/STAT3 signaling pathway
Silicosis is a systemic disease marked by diffuse pulmonary fibrosis resulting from prolonged inhalation of crystalline silica (CS) dust. This study aimed to examine the effects of anisodamine (ANI) on pulmonary inflammation and fibrosis in silicosis, as well as to elucidate the underlying molecular...
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Elsevier
2025-01-01
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| Series: | Ecotoxicology and Environmental Safety |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0147651324016105 |
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| author | Meng Liu Hui Liu Hong Kang Juan Wu Puhua Xing Xiaorui Ding Yangyang Wei Xiaomei Kong |
| author_facet | Meng Liu Hui Liu Hong Kang Juan Wu Puhua Xing Xiaorui Ding Yangyang Wei Xiaomei Kong |
| author_sort | Meng Liu |
| collection | DOAJ |
| description | Silicosis is a systemic disease marked by diffuse pulmonary fibrosis resulting from prolonged inhalation of crystalline silica (CS) dust. This study aimed to examine the effects of anisodamine (ANI) on pulmonary inflammation and fibrosis in silicosis, as well as to elucidate the underlying molecular mechanisms. Animal experiments demonstrated that ANI significantly reduced alveolar structure damage and the formation of silicosis nodules in affected mice, as confirmed by pathological slides. ANI inhibited the expression of tumor necrosis factor (TNF-α) in bronchoalveolar lavage fluid (BALF) while promoting the secretion of interleukin-4 (IL-4) and interleukin-10 (IL-10). Further molecular investigations indicated a strong link between pulmonary inflammation and fibrosis, showing decreased levels of α7nAChR and increased expression of phosphorylated Janus kinase 2 (JAK2) and phosphorylated transcription factor 3 (STAT3) in the lung tissues of mice exposed to CS. The relevant molecular alterations in the lung tissue of the model group of mice were reversed by ANI. Methyllycaconitine(MLA, α7nAChR inhibitor) and RO8191 (JAK2/STAT3 agonist) could reverse the therapeutic effect of ANI in silicosis and related molecular mechanisms. The results suggest that ANI may alleviate silicosis by inhibiting pulmonary inflammation and fibrosis through modulation of the JAK2/STAT3 signaling pathway, which is mediated by α7nAChR. Coal workers can utilize ANI early on to treat and prevent silicosis. |
| format | Article |
| id | doaj-art-5a96d7e40f8f480c936f0717fda6d387 |
| institution | Kabale University |
| issn | 0147-6513 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Elsevier |
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| series | Ecotoxicology and Environmental Safety |
| spelling | doaj-art-5a96d7e40f8f480c936f0717fda6d3872025-01-23T05:25:51ZengElsevierEcotoxicology and Environmental Safety0147-65132025-01-01289117534Anisodamine ameliorates crystalline silica-exposed pulmonary inflammation and fibrosis via the α7nAChR/JAK2/STAT3 signaling pathwayMeng Liu0Hui Liu1Hong Kang2Juan Wu3Puhua Xing4Xiaorui Ding5Yangyang Wei6Xiaomei Kong7NHC Key Laboratory of Pneumoconiosis, Shanxi Province Key Laboratory of Respiratory, Department of Respiratory and Critical Care Medicine, Shanxi Medical University Affiliated First Hospital, Taiyuan 030000, ChinaSchool of Public health, Shanxi Medical University, Taiyuan 030000, ChinaYangquan First People's Hospital, Yangquan 045000, ChinaNHC Key Laboratory of Pneumoconiosis, Shanxi Province Key Laboratory of Respiratory, Department of Respiratory and Critical Care Medicine, Shanxi Medical University Affiliated First Hospital, Taiyuan 030000, ChinaFirst School of Clinical Medicine, Shanxi Medical University, Taiyuan 030000, ChinaFirst School of Clinical Medicine, Shanxi Medical University, Taiyuan 030000, ChinaNHC Key Laboratory of Pneumoconiosis, Shanxi Province Key Laboratory of Respiratory, Department of Respiratory and Critical Care Medicine, Shanxi Medical University Affiliated First Hospital, Taiyuan 030000, China; Correspondence to: NHC Key Laboratory of Pneumoconiosis, 030000, ChinaNHC Key Laboratory of Pneumoconiosis, Shanxi Province Key Laboratory of Respiratory, Department of Respiratory and Critical Care Medicine, Shanxi Medical University Affiliated First Hospital, Taiyuan 030000, China; Correspondence to: NHC Key Laboratory of Pneumoconiosis, 030000, ChinaSilicosis is a systemic disease marked by diffuse pulmonary fibrosis resulting from prolonged inhalation of crystalline silica (CS) dust. This study aimed to examine the effects of anisodamine (ANI) on pulmonary inflammation and fibrosis in silicosis, as well as to elucidate the underlying molecular mechanisms. Animal experiments demonstrated that ANI significantly reduced alveolar structure damage and the formation of silicosis nodules in affected mice, as confirmed by pathological slides. ANI inhibited the expression of tumor necrosis factor (TNF-α) in bronchoalveolar lavage fluid (BALF) while promoting the secretion of interleukin-4 (IL-4) and interleukin-10 (IL-10). Further molecular investigations indicated a strong link between pulmonary inflammation and fibrosis, showing decreased levels of α7nAChR and increased expression of phosphorylated Janus kinase 2 (JAK2) and phosphorylated transcription factor 3 (STAT3) in the lung tissues of mice exposed to CS. The relevant molecular alterations in the lung tissue of the model group of mice were reversed by ANI. Methyllycaconitine(MLA, α7nAChR inhibitor) and RO8191 (JAK2/STAT3 agonist) could reverse the therapeutic effect of ANI in silicosis and related molecular mechanisms. The results suggest that ANI may alleviate silicosis by inhibiting pulmonary inflammation and fibrosis through modulation of the JAK2/STAT3 signaling pathway, which is mediated by α7nAChR. Coal workers can utilize ANI early on to treat and prevent silicosis.http://www.sciencedirect.com/science/article/pii/S0147651324016105AnisodamineSilicosisα7nAChRJAK2/STAT3, Inflammation |
| spellingShingle | Meng Liu Hui Liu Hong Kang Juan Wu Puhua Xing Xiaorui Ding Yangyang Wei Xiaomei Kong Anisodamine ameliorates crystalline silica-exposed pulmonary inflammation and fibrosis via the α7nAChR/JAK2/STAT3 signaling pathway Ecotoxicology and Environmental Safety Anisodamine Silicosis α7nAChR JAK2/STAT3, Inflammation |
| title | Anisodamine ameliorates crystalline silica-exposed pulmonary inflammation and fibrosis via the α7nAChR/JAK2/STAT3 signaling pathway |
| title_full | Anisodamine ameliorates crystalline silica-exposed pulmonary inflammation and fibrosis via the α7nAChR/JAK2/STAT3 signaling pathway |
| title_fullStr | Anisodamine ameliorates crystalline silica-exposed pulmonary inflammation and fibrosis via the α7nAChR/JAK2/STAT3 signaling pathway |
| title_full_unstemmed | Anisodamine ameliorates crystalline silica-exposed pulmonary inflammation and fibrosis via the α7nAChR/JAK2/STAT3 signaling pathway |
| title_short | Anisodamine ameliorates crystalline silica-exposed pulmonary inflammation and fibrosis via the α7nAChR/JAK2/STAT3 signaling pathway |
| title_sort | anisodamine ameliorates crystalline silica exposed pulmonary inflammation and fibrosis via the α7nachr jak2 stat3 signaling pathway |
| topic | Anisodamine Silicosis α7nAChR JAK2/STAT3, Inflammation |
| url | http://www.sciencedirect.com/science/article/pii/S0147651324016105 |
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