Pre-treatment with notoginsenoside R1 from Panax notoginseng protects against high-altitude-induced pulmonary edema by inhibiting pyroptosis through the NLRP3/caspase-1/GSDMD pathway

• Published in: Biomedicine & pharmacotherapy 2024-11, Vol.180, p.117512, Article 117512
• Main Authors: Huang, Demei, Wang, Yilan, Pei, Caixia, Zhang, Xiu, Shen, Zherui, Jia, Nan, Zhao, Sijing, Li, Guang, Wang, Zhenxing
• Format: Article
• Language: English
• Subjects: Altitude Sickness - complications; Altitude Sickness - drug therapy; Animals; Caspase 1 - metabolism; Disease Models, Animal; Gasdermins; Ginsenosides - pharmacology; High altitude pulmonary edema; Hypertension, Pulmonary; Hypobaric hypoxia; Lung - drug effects; Lung - metabolism; Lung - pathology; Male; NLR Family, Pyrin Domain-Containing 3 Protein - metabolism; NLRP3 inflammasome; Notoginsenoside R1; Oxidative Stress - drug effects; Panax notoginseng - chemistry; Phosphate-Binding Proteins; Pulmonary Edema - drug therapy; Pulmonary Edema - metabolism; Pulmonary Edema - prevention & control; Pyroptosis - drug effects; Rats; Rats, Sprague-Dawley; Signal Transduction - drug effects
• ISSN: 0753-3322; 1950-6007; 1950-6007
• DOI: 10.1016/j.biopha.2024.117512

High-altitude pulmonary edema (HAPE) is a potentially fatal condition that occurs when exposed to high-altitude hypoxia environments. Currently, there is no effective treatment for HAPE, and available interventions focus on providing relief. Notoginsenoside R1 (NGR1), a major active constituent of Panax notoginseng (Burkill) F.H.Chen (sānqī), has demonstrated heart and lung-protective effects under hypobaric hypoxia. However, there is a lack of clarity regarding the precise mechanisms that underlie the protective effects of NGR1 against inflammation. In this study, a rat model of HAPE was developed to assess the effect of NGR1 on this pathology. High-altitude hypoxia corresponding to 6000 m altitude was simulated with a hypobaric chamber. We found that NGR1 dose-dependently alleviated pulmonary oxidative stress damage and inflammatory response, and prevented acid-base balance disruption. In addition, NGR1 restored the expression levels of hypoxia-inducible factor-1 alpha, vascular endothelial growth factor, and aquaporin protein-5, correlated with the development of pulmonary edema induced by hypobaric hypoxia. Furthermore, NGR1 pre-treatment remarkably mitigated NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome-induced pyroptosis, and this effect was partially counteracted by the use of an NLRP3 agonist. Thus, NGR1 may exert a lung-protective effect against HAPE by ameliorating hypoxia-induced lung edema, oxidative damage, and inflammation through inhibition of the NLRP3/Caspase-1/ GSDMD signaling pathway. [Display omitted] •Pyroptosis may be a concomitant feature of HAPE in animals at 6000 m.•Notoginsenoside R1 from Panax notoginseng exhibits efficacy in protecting against pulmonary edema induced by hypobaric hypoxia.•Notoginsenoside R1 against HAPE through inhibition of the NLRP3/Caspase-1/ GSDMD signaling pathway.