Zhu Wenwen, Zhao Ningxia, Ma Yinghua, Zhang Wei, Ma Jiazi, Cao Mao, Yang Yong, Sun Shichao, Pan Zhifeng, Shao Hua, Du Zhongjun
College of Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine, Ji'nan, Shandong, China.
Department of Toxicology, Shandong Academy of Occupational Health and Occupational Medicine, Shandong First Medical University & Shandong Academy of Medical Sciences, Ji'nan, Shandong, China.
PLoS One. 2025 Jun 25;20(6):e0327255. doi: 10.1371/journal.pone.0327255. eCollection 2025.
Silicosis, a prevalent occupational disease caused by exposure to silica particles, currently lacks effective treatment. Traditional Chinese medicine (TCM), with its millennia of clinical application, offers potential therapeutic solutions. This study aimed to investigate the therapeutic effects of astragaloside IV (ASV) combined with quercetin (QUE) in silicosis, particular focus on their possible mechanisms involving autophagy modulation and pyroptosis regulation.
Rat silicosis models were established through silica particle exposure to evaluate the therapeutic effects of ASV and QUE coadministration over 28 days. We assessed pulmonary inflammatory and fibrotic markers while simultaneously analyzing autophagy and pyroptosis-related indicators to elucidate the underlying mechanism.
The ASV and QUE combination therapy significantly ameliorated silicosis pathology, demonstrating marked anti-inflammatory effects through the reduction of tumor necrosis factor alpha (TNF-α), transforming growth factor β1 (TGF-β1) and high mobility group box-1 (HMGB1) levels, while effectively attenuating pulmonary fibrosis as shown by decreased α-smooth muscle actin (α-SMA) and hydroxyproline (HYP) concentrations following 28 days of treatment. Mechanistic investigations revealed enhanced autophagy activity, evidenced by upregulated microtubule-associated protein 1 light chain 3 (LC3) II/I ratio and Beclin1 expression coupled with downregulated sequestosome 1 (SQSTM1/P62), along with suppressed pyroptosis as indicated by reduced interleukin-1β (IL-1β), interleukin-18 (IL-18), and Caspase-1 levels.
ASV combined with QUE could alleviate silica-induced pulmonary inflammation and fibrosis in rats, with the protective mechanism potentially mediated through enhanced autophagy activation and suppressed pyroptosis pathway.
矽肺是一种因接触二氧化硅颗粒而引发的常见职业病，目前缺乏有效的治疗方法。有着数千年临床应用历史的传统中药提供了潜在的治疗方案。本研究旨在探讨黄芪甲苷（ASV）联合槲皮素（QUE）对矽肺的治疗效果，特别关注其在自噬调节和焦亡调控方面的可能机制。
通过二氧化硅颗粒暴露建立大鼠矽肺模型，以评估ASV和QUE联合给药28天的治疗效果。我们评估了肺部炎症和纤维化标志物，同时分析自噬和焦亡相关指标以阐明潜在机制。
ASV与QUE联合治疗显著改善了矽肺病理，通过降低肿瘤坏死因子α（TNF-α）、转化生长因子β1（TGF-β1）和高迁移率族蛋白B1（HMGB1）水平显示出显著的抗炎作用，同时在治疗28天后，α-平滑肌肌动蛋白（α-SMA）和羟脯氨酸（HYP）浓度降低，有效减轻了肺纤维化。机制研究显示自噬活性增强，表现为微管相关蛋白1轻链3（LC3）II/I比值上调和Beclin1表达增加，同时sequestosome 1（SQSTM1/P62）下调，以及焦亡受到抑制，表现为白细胞介素-1β（IL-1β）、白细胞介素-18（IL-18）和半胱天冬酶-1水平降低。
ASV联合QUE可减轻二氧化硅诱导的大鼠肺部炎症和纤维化，其保护机制可能通过增强自噬激活和抑制焦亡途径介导。
