l-Arginine, as an essential amino acid, is a potential substitute for treating COPD via regulation of ROS/NLRP3/NF-κB signaling pathway

Abstract

Abstract Backgrounds Chronic obstructive pulmonary disease (COPD) is a frequent and common disease in clinical respiratory medicine and its mechanism is unclear. The purpose of this study was to find the new biomarkers of COPD and elucidate its role in the pathogenesis of COPD. Analysis of metabolites in plasma of COPD patients were performed by ultra-high performance liquid chromatography (UPLC) and quadrupole time-of-flight mass spectrometry (TOF–MS). The differential metabolites were analyzed and identified by multivariate analysis between COPD patients and healthy people. The role and mechanisms of the differential biomarkers in COPD were verified with COPD rats, arginosuccinate synthetase 1 (ASS-l) KO mice and bronchial epithelial cells (BECs). Meanwhile, whether the differential biomarkers can be the potential treatment targets for COPD was also investigated. 85 differentials metabolites were identified between COPD patients and healthy people by metabonomic. Results l-Arginine (LA) was the most obvious differential metabolite among the 85 metabolites. Compare with healthy people, the level of LA was markedly decreased in serum of COPD patients. It was found that LA had protective effects on COPD with in vivo and in vitro experiments. Silencing Ass-1, which regulates LA metabolism, and α-methy-dl-aspartic (NHLA), an Ass-1 inhibitor, canceled the protective effect of LA on COPD. The mechanism of LA in COPD was related to the inhibition of ROS/NLRP3/NF-κB signaling pathway. It was also found that exogenous LA significantly improved COPD via regulation of ROS/NLRP3/NF-κB signaling pathway. l-Arginine (LA) as a key metabolic marker is identified in COPD patients and has a protective effect on COPD via regulation of ROS/NLRP3/NF-κB signaling pathway. Conclusion LA may be a novel target for the treatment of COPD and also a potential substitute for treating COPD.

Keywords

• Metabolic markers
• COPD
• l-Arginine