Abstract
—Emodin, the effective component of the traditional Chinese medicine Dahuang, has anti-inflammatory effects. However, the protective effects and potential mechanisms of emodin are not clear. This study investigated the protective effects and potential mechanisms of emodin on lipopolysaccharide (LPS)-induced acute lung injury (ALI) in vitro and in vivo. In vivo, we designed an LPS-induced ALI rat model. In vitro, we chose the J774A.1 cell line to establish an inflammatory cellular model, and knocked down NOD-like receptor family pyrin domain containing 3 (NLRP3) using small interfering RNA. The mRNA and protein expression of NLRP3, a C-terminal caspase recruitment domain (ASC), caspase 1 (CASP1), and gasdermin D (GSDMD) in cells and lung tissues were detected by western blot and real-time quantitative polymerase chain reaction (PCR). The expression levels of interleukin 1 beta (IL-1β) and IL-18 in the serum and supernatant were determined by the enzyme-linked immunosorbent assay. The degree of pathological injury in lung tissue was evaluated by hematoxylin and eosin (H&E) staining. In vitro, we demonstrated that emodin could inhibit NLRP3 and then inhibit the expression of ASC, CASP1, GSDMD, IL-1β, and IL-18. In vivo, we confirmed that emodin had protective effects on LPS-induced ALI and inhibitory effects on NLRP3 inflammasome -dependent pyroptosis. Emodin showed excellent protective effects against LPS-induced ALI by regulating the NLRP3 inflammasome-dependent pyroptosis signaling pathway.
Highlights
Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are the main causes of hypoxic respiratory failure during the hospitalization period in adults with high morbidity and mortality [1]
We showed that emodin may have protective effects on LPS-induced ALI by regulating the NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome-dependent pyroptosis signaling pathway
To assess the cytotoxicity of emodin on J774A.1 cells, we evaluated the viability of J774A.1 cells treated with different concentrations of emodin (10, 20, 40, 80, 160 μg/mL) after 24h according to the instructions of the Cell Counting Kit-8 (CCK-8) kit
Summary
Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are the main causes of hypoxic respiratory failure during the hospitalization period in adults with high morbidity and mortality [1]. The characteristics of ALI/ARDS are infiltration of inflammatory cells, imbalance of the inflammatory response, and excess production of inflammatory mediators in lung tissue, which induce destruction of the bloodalveolar barrier and pulmonary edema [2]. There is no specific drug for the treatment of ALI, so it is important to explore novel drugs and targets that can effectively treat lung injury. Pyroptosis is a newly discovered pro-inflammatory programmed cell death mode. When the body is infected, the NOD-like receptor family pyrin domain containing 3 (NLRP3) recruits pro-caspase-1 and apoptosis-associated speck-like protein containing a caspase-recruitment domain (ASC) to form the NLRP3 inflammasome. The NLRP3 inflammasome processes pro-caspase-1 (CASP1) into mature CASP1, which activates gasdermin D (GSDMD) to form holes in the cell membrane [3]. Inhibition of NLRP3 inflammasome can alleviate ALI [8], indicating that the NLRP3 inflammasome may be a therapeutic target in ALI
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