{"title":"Cytoprotective role of resveratrol in cigarette smoke-induced pyroptosis through Nrf2 pathway activation","authors":"Mengyu Zhang, Chenyang Hu, Guang Yang, Yajie Hu, Yiqing Qu","doi":"10.1016/j.cstres.2025.100107","DOIUrl":null,"url":null,"abstract":"<div><div>Resveratrol, a natural polyphenolic compound, has garnered increasing attention due to its antioxidant and anti-inflammatory properties. In this study, we investigated its protective role against cigarette smoke extract (CSE)-induced pyroptosis in human bronchial epithelial cell lines (BEAS-2B, 16HBE, and A549) and a chronic cigarette smoke (CS)-exposed mouse model. CS exposure is a major pathogenic factor in chronic obstructive pulmonary disease, primarily through promoting oxidative stress, inflammation, and pyroptotic cell death. Our results demonstrate that resveratrol enhances the activation of the nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway, upregulating downstream antioxidant enzymes such as HO-1 and NQO1. This activation mitigates oxidative stress and inhibits the activation of the TXNIP/NLRP3/caspase-1 inflammasome axis. <em>In vitro</em>, resveratrol reduced ROS accumulation and proinflammatory cytokine release in CSE-stimulated human bronchial epithelial cells. <em>In vivo</em>, resveratrol partially restored lung function and redox homeostasis in CS-exposed mice. Moreover, mechanistic analyses revealed that resveratrol upregulates miR-200a expression, which directly targets Keap1, thereby relieving its inhibition of Nrf2. These findings suggest that resveratrol alleviates CSE-induced pyroptosis by modulating the miR-200a/Keap1/Nrf2 axis and may serve as a potential therapeutic strategy for smoking-related airway diseases. However, additional clinical studies are necessary to confirm its efficacy.</div></div>","PeriodicalId":9684,"journal":{"name":"Cell Stress & Chaperones","volume":"30 5","pages":"Article 100107"},"PeriodicalIF":3.2000,"publicationDate":"2025-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cell Stress & Chaperones","FirstCategoryId":"99","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S1355814525000525","RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"CELL BIOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Resveratrol, a natural polyphenolic compound, has garnered increasing attention due to its antioxidant and anti-inflammatory properties. In this study, we investigated its protective role against cigarette smoke extract (CSE)-induced pyroptosis in human bronchial epithelial cell lines (BEAS-2B, 16HBE, and A549) and a chronic cigarette smoke (CS)-exposed mouse model. CS exposure is a major pathogenic factor in chronic obstructive pulmonary disease, primarily through promoting oxidative stress, inflammation, and pyroptotic cell death. Our results demonstrate that resveratrol enhances the activation of the nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway, upregulating downstream antioxidant enzymes such as HO-1 and NQO1. This activation mitigates oxidative stress and inhibits the activation of the TXNIP/NLRP3/caspase-1 inflammasome axis. In vitro, resveratrol reduced ROS accumulation and proinflammatory cytokine release in CSE-stimulated human bronchial epithelial cells. In vivo, resveratrol partially restored lung function and redox homeostasis in CS-exposed mice. Moreover, mechanistic analyses revealed that resveratrol upregulates miR-200a expression, which directly targets Keap1, thereby relieving its inhibition of Nrf2. These findings suggest that resveratrol alleviates CSE-induced pyroptosis by modulating the miR-200a/Keap1/Nrf2 axis and may serve as a potential therapeutic strategy for smoking-related airway diseases. However, additional clinical studies are necessary to confirm its efficacy.
期刊介绍:
Cell Stress and Chaperones is an integrative journal that bridges the gap between laboratory model systems and natural populations. The journal captures the eclectic spirit of the cellular stress response field in a single, concentrated source of current information. Major emphasis is placed on the effects of climate change on individual species in the natural environment and their capacity to adapt. This emphasis expands our focus on stress biology and medicine by linking climate change effects to research on cellular stress responses of animals, micro-organisms and plants.