Anisodamine ameliorates crystalline silica-exposed pulmonary inflammation and fibrosis via the α7nAChR/JAK2/STAT3 signaling pathway.

IF 6.2 2区 环境科学与生态学 Q1 ENVIRONMENTAL SCIENCES
Meng Liu, Hui Liu, Hong Kang, Juan Wu, Puhua Xing, Xiaorui Ding, Yangyang Wei, Xiaomei Kong
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引用次数: 0

Abstract

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.

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来源期刊
CiteScore
12.10
自引率
5.90%
发文量
1234
审稿时长
88 days
期刊介绍: Ecotoxicology and Environmental Safety is a multi-disciplinary journal that focuses on understanding the exposure and effects of environmental contamination on organisms including human health. The scope of the journal covers three main themes. The topics within these themes, indicated below, include (but are not limited to) the following: Ecotoxicology、Environmental Chemistry、Environmental Safety etc.
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