Graduate School, Hunan University of Chinese Medicine, Changsha, China.
Department of Oncology, The Affiliated Hospital of Hunan Academy of Traditional Chinese Medicine, Changsha, China.
Biochem Biophys Res Commun. 2024 Dec 20;739:150946. doi: 10.1016/j.bbrc.2024.150946. Epub 2024 Nov 6.
Ferroptosis plays a key role in the development of chronic obstructive pulmonary disease (COPD). Whether ginsenoside Rg1 improves cigarette smoke-induced COPD or whether ginsenoside Rg1 improves COPD by inhibiting ferroptosis remains unknown.
BEAS-2B cells were exposed to cigarette solution (CSE) for 24 h and treated with ginsenoside Rg1, the ferroptosis inhibitor Fer-1, and the PERK inhibitor GSK. Cell viability, endoplasmic reticulum stress, mitochondrial morphology, membrane potential, reactive oxygen species (ROS), iron levels, and the expression of related proteins were detected using corresponding methods. A COPD mouse model was constructed using cigarette smoke (CS). Ginsenoside Rg1 and GSK were administered via tube feeding 15 days after successful modeling. Mouse lung tissues were evaluated by HE staining. The expression of inflammatory markers, ROS, iron content, and related proteins was detected using corresponding methods.
The results demonstrated that in the CSE-exposed BEAS-2B cell model and CS-induced mouse COPD model, the expression levels of endoplasmic reticulum stress (ERS)-related factors such as GRP78 were increased, while those of the antioxidant markers GPX4 and GSH were significantly decreased. Ginsenoside Rg1 improved emphysema and inflammation by inhibiting ferroptosis in vivo and in vitro. Using a PERK inhibitor, we found that ginsenoside Rg1 inhibited ferroptosis in vivo and in vitro by regulating ERS.
This study showed that ginsenoside Rg1 alleviates cigarette smoke-induced COPD by regulating the PERK/ATF4 axis to inhibit ERS and ferroptosis.
铁死亡在慢性阻塞性肺疾病（COPD）的发展中起着关键作用。人参皂苷 Rg1 是否能改善香烟烟雾诱导的 COPD，或者人参皂苷 Rg1 是否通过抑制铁死亡来改善 COPD，目前尚不清楚。
将 BEAS-2B 细胞暴露于香烟溶液（CSE）中 24 小时，并用人参皂苷 Rg1、铁死亡抑制剂 Fer-1 和 PERK 抑制剂 GSK 处理。使用相应的方法检测细胞活力、内质网应激、线粒体形态、膜电位、活性氧（ROS）、铁水平和相关蛋白的表达。使用香烟烟雾（CS）构建 COPD 小鼠模型。造模成功后 15 天，通过管饲给予人参皂苷 Rg1 和 GSK。通过 HE 染色评估小鼠肺组织。使用相应的方法检测炎症标志物、ROS、铁含量和相关蛋白的表达。
结果表明，在 CSE 暴露的 BEAS-2B 细胞模型和 CS 诱导的小鼠 COPD 模型中，内质网应激（ERS）相关因子如 GRP78 的表达水平增加，而抗氧化标记物 GPX4 和 GSH 的表达水平显著降低。人参皂苷 Rg1 通过体内和体外抑制铁死亡改善肺气肿和炎症。使用 PERK 抑制剂，我们发现人参皂苷 Rg1 通过调节 ERS 抑制体内和体外的铁死亡。
这项研究表明，人参皂苷 Rg1 通过调节 PERK/ATF4 轴抑制 ERS 和铁死亡来缓解香烟烟雾引起的 COPD。
