Jiucui Li1, Kongmiao Lu1, Fenglan Sun1, Shanjuan Tan1, Xiao Zhang1, Wei Sheng1, Wanming Hao1, Min Liu2, Weihong Lv3, Wei Han4. 1. Qingdao Municipal Hospital, School of Medicine, Qingdao University, No. 1, Jiaozhou Road, Qingdao, 266011, Shandong, China. 2. Qingdao Municipal Hospital, School of Medicine, Qingdao University, No. 1, Jiaozhou Road, Qingdao, 266011, Shandong, China. min.1iu@yandex.com. 3. Qingdao Municipal Hospital, School of Medicine, Qingdao University, No. 1, Jiaozhou Road, Qingdao, 266011, Shandong, China. lvhona12@protonmail.com. 4. Qingdao Municipal Hospital, School of Medicine, Qingdao University, No. 1, Jiaozhou Road, Qingdao, 266011, Shandong, China. sallyhan1@163.com.
Abstract
BACKGROUND: Acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) induces uncontrolled and self-amplified pulmonary inflammation, and has high morbidity and mortality rates in critically ill patients. In recent years, many bioactive ingredients extracted from herbs have been reported to effectively ameliorate ALI/ARDS via different mechanisms. Ferroptosis, categorized as regulated necrosis, is more immunogenic than apoptosis and contributes to the progression of ALI. In this study, we examined the impact of panaxydol (PX), isolated from the roots of Panax ginseng, on lipopolysaccharide (LPS)-induced ALI in mice. METHODS: In vivo, the role of PX on LPS-induced ALI in mice was tested by determination of LPS-induced pulmonary inflammation, pulmonary edema and ferroptosis. In vitro, BEAS-2B cells were used to investigate the molecular mechanisms by which PX functions via determination of inflammation, ferroptosis and their relationship. RESULTS: Administration of PX protected mice against LPS-induced ALI, including significantly ameliorated lung pathological changes, and decreased the extent of lung edema, inflammation, and ferroptosis. In vitro, PX inhibited LPS-induced ferroptosis and inflammation in bronchial epithelial cell line BEAS-2B cells. The relationship between ferroptosis and inflammation was investigated. The results showed that ferroptosis mediated inflammation in LPS-treated BEAS-2B cells, and PX might ameliorate LPS-induced inflammation via inhibiting ferroptosis. Meanwhile, PX could upregulate Keap1-Nrf2/HO-1 pathway, and selective inhibition of Keap1-Nrf2/HO-1 pathway significantly abolished the anti-ferroptotic and anti-inflammatory functions of PX in LPS-treated cells. CONCLUSION: PX attenuates ferroptosis against LPS-induced ALI via Keap1-Nrf2/HO-1 pathway, and is a promising novel therapeutic candidate for ALI.
BACKGROUND: Acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) induces uncontrolled and self-amplified pulmonary inflammation, and has high morbidity and mortality rates in critically ill patients. In recent years, many bioactive ingredients extracted from herbs have been reported to effectively ameliorate ALI/ARDS via different mechanisms. Ferroptosis, categorized as regulated necrosis, is more immunogenic than apoptosis and contributes to the progression of ALI. In this study, we examined the impact of panaxydol (PX), isolated from the roots of Panax ginseng, on lipopolysaccharide (LPS)-induced ALI in mice. METHODS: In vivo, the role of PX on LPS-induced ALI in mice was tested by determination of LPS-induced pulmonary inflammation, pulmonary edema and ferroptosis. In vitro, BEAS-2B cells were used to investigate the molecular mechanisms by which PX functions via determination of inflammation, ferroptosis and their relationship. RESULTS: Administration of PX protected mice against LPS-induced ALI, including significantly ameliorated lung pathological changes, and decreased the extent of lung edema, inflammation, and ferroptosis. In vitro, PX inhibited LPS-induced ferroptosis and inflammation in bronchial epithelial cell line BEAS-2B cells. The relationship between ferroptosis and inflammation was investigated. The results showed that ferroptosis mediated inflammation in LPS-treated BEAS-2B cells, and PX might ameliorate LPS-induced inflammation via inhibiting ferroptosis. Meanwhile, PX could upregulate Keap1-Nrf2/HO-1 pathway, and selective inhibition of Keap1-Nrf2/HO-1 pathway significantly abolished the anti-ferroptotic and anti-inflammatory functions of PX in LPS-treated cells. CONCLUSION: PX attenuates ferroptosis against LPS-induced ALI via Keap1-Nrf2/HO-1 pathway, and is a promising novel therapeutic candidate for ALI.
Authors: Jesús Villar; Jesús Blanco; José Manuel Añón; Antonio Santos-Bouza; Lluís Blanch; Alfonso Ambrós; Francisco Gandía; Demetrio Carriedo; Fernando Mosteiro; Santiago Basaldúa; Rosa Lidia Fernández; Robert M Kacmarek Journal: Intensive Care Med Date: 2011-10-14 Impact factor: 17.440
Authors: Scott J Dixon; Kathryn M Lemberg; Michael R Lamprecht; Rachid Skouta; Eleina M Zaitsev; Caroline E Gleason; Darpan N Patel; Andras J Bauer; Alexandra M Cantley; Wan Seok Yang; Barclay Morrison; Brent R Stockwell Journal: Cell Date: 2012-05-25 Impact factor: 41.582