Yin Changfeng, Tian Yushan, Yan An, Wang Hongjuan, Lu Fengjun, Li Xianmei, Li Xiao, Han Shulei, Miao Ruijuan, Chen Huan, Li Di, Hou Hongwei, Hu Qingyuan
China National Tobacco Quality Supervision & Test Center, Zhengzhou, China.
Beijing Life Science Academy, Beijing, China.
Front Pharmacol. 2024 Dec 17;15:1503283. doi: 10.3389/fphar.2024.1503283. eCollection 2024.
Chronic obstructive pulmonary disease (COPD) is a disease with severe therapeutic obstacles and high worldwide death rate. COPD progresses predominantly through inflammatory response followed by fibrotic destruction. Quercetin (Que), recognized for its anti-inflammatory effects, presents significant promise as a therapeutic candidate for COPD therapy. However, poor water solubility and low bioavailability of Que hinder its further clinical application. Liposomes are renowned for their unique structure and function, which provided an efficient approach for the delivery of Que in various drug delivery systems. This study was aim to prepare a novel Que liposome (Que-lipo) and administrated via intratracheal (i.t.) with cigarette smoke induced COPD mice. The underlying therapeutic mechanisms against lung damage of Que-lipo were explored.
Que-lipo were prepared based on thin film dispersion method and administrated via intratracheal administration. The cigarette smoke induced COPD mice were established and a comprehensive approach was employed to explore the inflammation, pulmonary function and histopathology of lung after i.t. administration of Que-lipo, including enzyme-linked immunosorbent assay, histopathology and immunohistochemistry, reverse transcription-quantitative polymerase chain reaction.
Que-lipo not only improved the solubility and biocompatibility of Que but also demonstrated effective cellular uptake . The inflammation, pulmonary function and pathological condition of lung were improved after i.t. administration of Que-lipo. Que-lipo also regulated the expression of key apoptosis-associated proteins such as Bcl-2 and caspase-3/7, leading to significant inhibition of apoptotic activity in COPD. Furthermore, Que-lipo markedly enhanced its ability to alleviate lung inflammation and fibrosis symptoms by modulating inflammation-related factors and fibrosis signaling molecules. The potential mechanisms of Que-lipo in treating COPD were elucidated, including the suppression of the NLRP3/IL-1β inflammasome pathway and the TGF-β1-related fibrosis signaling pathway.
慢性阻塞性肺疾病（COPD）是一种治疗障碍严重且全球死亡率高的疾病。COPD主要通过炎症反应继而纤维化破坏进展。槲皮素（Que）因其抗炎作用而闻名，作为COPD治疗的候选药物具有巨大潜力。然而，槲皮素的水溶性差和生物利用度低阻碍了其进一步的临床应用。脂质体以其独特的结构和功能而闻名，这为在各种药物递送系统中递送槲皮素提供了一种有效方法。本研究旨在制备一种新型槲皮素脂质体（Que-lipo），并通过气管内（i.t.）给药于香烟烟雾诱导的COPD小鼠，探索Que-lipo对肺损伤的潜在治疗机制。
基于薄膜分散法制备Que-lipo，并通过气管内给药。建立香烟烟雾诱导的COPD小鼠模型，并采用综合方法探讨i.t.给予Que-lipo后肺的炎症、肺功能和组织病理学，包括酶联免疫吸附测定、组织病理学和免疫组织化学、逆转录定量聚合酶链反应。
Que-lipo不仅提高了槲皮素的溶解度和生物相容性，还表现出有效的细胞摄取。i.t.给予Que-lipo后，肺的炎症、肺功能和病理状况得到改善。Que-lipo还调节了关键凋亡相关蛋白如Bcl-2和caspase-3/7的表达，导致COPD中凋亡活性的显著抑制。此外，Que-lipo通过调节炎症相关因子和纤维化信号分子，显著增强了其减轻肺部炎症和纤维化症状的能力。阐明了Que-lipo治疗COPD的潜在机制，包括抑制NLRP3/IL-1β炎性小体途径和TGF-β1相关纤维化信号途径。
