Abstract
Sinomenine (SIN) is a bioactive alkaloid extracted from the Chinese medicinal plant Sinomenium acutum, which is widely used in the clinical treatment of rheumatoid arthritis (RA). However, its role in acute lung injury (ALI) is unclear. In this study, we investigate the role of SIN in lipopolysaccharide (LPS)-induced ALI in mice. After ALI, lung water content and histological signs of pulmonary injury were attenuated, whereas the PaO2/FIO2 (P/F) ratios were elevated significantly in the mice pretreated with SIN. Additionally, SIN markedly inhibited inflammatory cytokine TNF-α and IL-1β expression levels as well as neutrophil infiltration in the lung tissues of the mice. Microarray analysis and real-time PCR showed that SIN treatment upregulated adenosine A2A receptor (A2AR) expression, and the protective effect of SIN was abolished in A2AR knockout mice. Further investigation in isolated mouse neutrophils confirmed the upregulation of A2AR by SIN and showed that A2AR-cAMP-PKA signaling was involved in the anti-inflammatory effect of SIN. Taken together, these findings demonstrate an A2AR-associated anti-inflammatory effect and the protective role of SIN in ALI, which suggests a potential novel approach to treat ALI.
Highlights
Acute lung injury (ALI) is a life-threatening condition that can develop during the course of several clinical situations such as pneumonia, major trauma, acid aspiration, and sepsis [1,2].The pathogenesis of ALI is characterized by an influx of protein-rich fluid into the interstitial and intra-alveolar spaces as a result of increased permeability of the alveolar-capillary barrier in conjunction with excessive invasion of inflammatory cells — neutrophils [3,4,5]
At 24 hour post-ALI, neutrophil infiltration into the lung tissues was detected with the neutrophil-specific marker CD177
30 mg/kg SIN treatment significantly reduced the CD177-positive cells, which indicated that neutrophil recruitment into lung tissue of mice was suppressed to some extent
Summary
The pathogenesis of ALI is characterized by an influx of protein-rich fluid into the interstitial and intra-alveolar spaces as a result of increased permeability of the alveolar-capillary barrier in conjunction with excessive invasion of inflammatory cells — neutrophils [3,4,5]. The inflammatory response plays an essential role in the progression of ALI. SIN has been used in the treatment of rheumatoid arthritis due to its role in inhibition of leukocytes migration across blood vessel walls, and its histamine-releasing and anti-angiogenic properties [6,7,8]. Studies in vitro have shown that SIN is able to inhibit lymphocyte proliferation and antibody production by B cells and potently reduce the production of inflammatory factors by macrophages [9,10,11].
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
