Molecular Toxicology Key Laboratory of Sichuan Provincial Education office, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu 610041, China.
College of Biomass Science and Engineering and Healthy Food Evaluation Research Center, Sichuan University, Chengdu 610065, China.
Phytomedicine. 2024 Dec;135:156238. doi: 10.1016/j.phymed.2024.156238. Epub 2024 Nov 16.
Silicosis, an interstitial lung disease caused by inhalation of silica particles, poses a significant health concern globally. Green tea polyphenol (TP) stands out as a promising therapeutic candidate, yet its specific protective effects and in-depth mechanisms against silicosis have not been thoroughly investigated.
This study aimed to systematically assess the protective potential of TP against silicosis and to elucidate the underlying mechanisms of its action.
A combination of physiological, transcriptomic, molecular, and computational techniques was employed. HPLC was used to identify the components of TP, and its antioxidant properties were tested with DPPH and ABTS assays. The effects of TP on lung injury were assessed in silicosis mice using histopathology, qRT-PCR, and western blot. Transcriptomic analysis was applied to explore the differentially expressed genes and pathways in response to TP intervention. In vitro studies with mouse alveolar macrophages (MH-S) examined TP's effects on cell viability, proliferation, apoptosis, and inflammation responses. Integrated qRT-PCR, western blot, immunohistochemistry, and molecular docking were performed to confirm the molecular mechanism underlying the protective effects of TP against silicosis.
TP effectively attenuated pulmonary inflammation and fibrosis in silicosis mice, as evidenced by significant reductions in inflammation and fibrotic markers. Moreover, TP's therapeutic benefits were linked to its cytoprotective effects on alveolar macrophages, notably its ability to protect MH-S cells from silica particle-induced apoptosis, inhibition of proliferation, and inflammatory response, underscoring its targeted protective effects at the cellular level. Mechanistically, TP exerted its anti-silicosis activity by targeting key pathways implicated in inflammatory responses, notably through the inhibition of the IL-17/NF-κB p65 signaling cascade. Molecular docking simulations corroborated these findings, demonstrating favorable binding affinities between TP's bioactive components (EGC, ECG, and EGCG) and crucial proteins (IL-17A, IL-17F, p65, TNF-α, IL-6, and IL-1β) involved in the IL-17/NF-κB p65 signaling pathway. This pathway inhibition led to a significant decrease in the production of pro-inflammatory cytokines, such as TNF-α, IL-6, and IL-1β, thus mitigated silicosis.
TP demonstrates efficacy in alleviating silica particle-induced lung injury by suppressing inflammation through the IL-17/NF-κB p65 signaling pathway, underscoring its potential as a valuable natural compound for silicosis management.
矽肺是一种由吸入矽尘颗粒引起的间质性肺疾病，在全球范围内构成重大健康威胁。绿茶多酚（TP）作为一种有前途的治疗候选物脱颖而出，但它对矽肺的具体保护作用及其作用机制尚未得到深入研究。
本研究旨在系统评估 TP 对矽肺的保护潜力，并阐明其作用机制。
采用生理、转录组学、分子和计算技术相结合的方法。HPLC 用于鉴定 TP 的成分，并用 DPPH 和 ABTS 测定法测试其抗氧化性能。用组织病理学、qRT-PCR 和 Western blot 评估 TP 对矽肺小鼠肺损伤的影响。采用转录组学分析探讨 TP 干预后差异表达基因和通路。用小鼠肺泡巨噬细胞（MH-S）进行体外研究，观察 TP 对细胞活力、增殖、凋亡和炎症反应的影响。整合 qRT-PCR、Western blot、免疫组织化学和分子对接实验，以确认 TP 对矽肺保护作用的分子机制。
TP 可有效减轻矽肺小鼠的肺部炎症和纤维化，炎症和纤维化标志物显著降低。此外，TP 的治疗益处与其对肺泡巨噬细胞的细胞保护作用有关，尤其是其保护 MH-S 细胞免受矽尘颗粒诱导的凋亡、抑制增殖和炎症反应的能力，突出了其在细胞水平的靶向保护作用。在机制上，TP 通过靶向参与炎症反应的关键途径发挥抗矽肺活性，特别是通过抑制 IL-17/NF-κB p65 信号级联。分子对接模拟实验证实了这一发现，表明 TP 的生物活性成分（EGC、ECG 和 EGCG）与参与 IL-17/NF-κB p65 信号通路的关键蛋白（IL-17A、IL-17F、p65、TNF-α、IL-6 和 IL-1β）之间具有良好的结合亲和力。该途径的抑制导致促炎细胞因子（如 TNF-α、IL-6 和 IL-1β）的产生显著减少，从而缓解矽肺。
TP 通过抑制 IL-17/NF-κB p65 信号通路减轻矽尘颗粒诱导的肺损伤，从而发挥抗炎作用，表明其作为矽肺管理有价值的天然化合物的潜力。
