Key Laboratory of Xinjiang Phytomedicine Resource and Utilization, Ministry of Education, College of Pharmacy, Shihezi University, Shihezi 832002, China.
State-Province Key Laboratory of Biomedicine-Pharmaceutics of China, Department of Medicinal Chemistry and Natural Medicine Chemistry, Harbin Medical University, Harbin 150081, China.
Int J Mol Sci. 2024 Feb 3;25(3):1875. doi: 10.3390/ijms25031875.
Acute lung injury (ALI) is a serious inflammatory disease with high morbidity and mortality. Rosavin is an anti-inflammatory and antioxidant phenylpropanoid and glucoside, which is isolated from Rhodiola rosea L. However, its potential molecular mechanisms and whether it has protective effects against lipopolysaccharide (LPS)-induced ALI remain to be elucidated. To assess the in vitro anti-inflammatory effects and anti-lung injury activity of rosavin, RAW264.7 and A549 cells were stimulated using 1 μg/mL LPS. Rosavin attenuated LPS-induced activation of the TLR-4/NF-κB signaling pathway in RAW264.7 cells and inhibited LPS-induced release of inflammatory factors in A549 cells. A mouse model of acute lung injury was constructed by intraperitoneal injection of 5 mg/kg LPS to observe the therapeutic effect of rosavin. Transcriptomics analysis and Western blot assays were utilized to verify the molecular mechanism, rosavin (20, 40, and 80 mg/kg) dose-dependently ameliorated histopathological alterations, reduced the levels of inflammatory factors, and inhibited the TLR-4/NF-κB/MAPK signaling pathway and apoptosis activation. Rosavin is a promising therapeutic candidate for acute lung injury by inhibiting the TLR-4/NF-κB/MAPK pathway.
急性肺损伤（ALI）是一种严重的炎症性疾病，具有高发病率和死亡率。罗萨文是一种具有抗炎和抗氧化作用的苯丙素和糖苷，它从红景天中分离出来。然而，它的潜在分子机制以及它是否对脂多糖（LPS）诱导的 ALI 具有保护作用仍有待阐明。为了评估罗萨文的体外抗炎作用和抗肺损伤活性，用 1μg/ml LPS 刺激 RAW264.7 和 A549 细胞。罗萨文减弱了 LPS 诱导的 RAW264.7 细胞中 TLR-4/NF-κB 信号通路的激活，并抑制了 LPS 诱导的 A549 细胞中炎症因子的释放。通过腹腔注射 5mg/kg LPS 构建急性肺损伤小鼠模型，观察罗萨文的治疗效果。通过转录组学分析和 Western blot 分析验证了分子机制，罗萨文（20、40 和 80mg/kg）剂量依赖性地改善了组织病理学改变，降低了炎症因子水平，并抑制了 TLR-4/NF-κB/MAPK 信号通路和细胞凋亡的激活。罗萨文通过抑制 TLR-4/NF-κB/MAPK 通路，有望成为急性肺损伤的治疗候选药物。
