The Protective Effect of Artesunate on LPS-Induced Acute Respiratory Distress Syndrome through Inhibiting NLRP3 Inflammasome Signaling

Abstract

Background. Artesunate (AS) is a derivative of artemisinin that can exert anti-inflammatory effects. This study aims to explore the effect of AS on lipopolysaccharide (LPS)-induced acute respiratory distress syndrome (ARDS). Methods. The newborn mice were used for experimental ARDS model establishment by intraperitoneal injection of LPS (10 mg/kg) into mice with or without AS (20 mg/kg) pretreatment. After that, the pathological morphology of mouse lung tissue was observed by H&E staining. The content of inflammatory factors in serum was measured by ELISA and mRNA expression and lung tissue was determined by qRT-PCR. The expression of NLRP3 inflammasome and related proteins in lung tissue was confirmed by immunohistochemistry and Western blot. Results. AS treatment effectively alleviated the LPS-induced lung injury and pulmonary edema, and reduced the expression of IL-1β, IL-18, IL-6, IL-8, MCP-1, and TNF-α in serum and lung tissues of experimental ARDS mice. In addition, AS treatment reduced the expression of NLRP3, ASC, and caspase-1 in lung tissues of experimental ARDS mice. Conclusion. AS alleviated LPS-induced lung injury in ARDS mice by inhibiting the activation of NLRP3 inflammasome.

Signaling pathways and potential therapeutic targets in acute respiratory distress syndrome (ARDS)

“…The molecular BAP31 as well as Schisandrin B have presented therapeutic value by targeting MyD88 to reduce NF-κB activation in ALI mice [ 240 , 241 ]. Moreover, there are a variety of targets that inhibit NF-κB signaling to negatively regulate NLRP3 inflammasome, such as Loganin [ 242 ], Dapagliflozin [ 243 ], Hederasaponin C [ 244 ], Artesunate [ 245 ], Syringaresinol [ 246 ], all of which have been studied in preclinical models of ALI/ARDS. Of note, the neutrophil elastase inhibitor Sivelestat and Simvastatin, two promising therapeutic drugs for treating ALI/ARDS, were also proven to target NF-κB inhibition in LPS-induced ALI [ 247 , 248 ].…”

A new therapeutic strategy in NLRP3 inflammasome – mediated inflammatory diseases

“…Artesunato, un derivado de la lactona sesquiterpenica artemisinina obtenida de la especie Artemisia annua L. (Asteraceae), redujo significativamente la neuroinflamación en un modelo de lesión cerebral traumatica, por sus efectos inhibitorios en la activación de NF-kB, en la liberación de citoquinas proinflamatorias y en la activación del inflamasoma NLRP3 (80). Los efectos protectores de este compuesto fueron también descritos en un modelo murino de distress respiratorio agudo (81).…”