<p>Emodin Protects Against Acute Pancreatitis-Associated Lung Injury by Inhibiting NLPR3 Inflammasome Activation via Nrf2/HO-1 Signaling</p>

Abstract

Lung injury is a common complication of acute pancreatitis (AP), which leads to the development of acute respiratory distress syndrome and causes high mortality. In the present study, we investigated the therapeutic effect of emodin on AP-induced lung injury and explored the molecular mechanisms involved. Materials and Methods: Thirty male Sprague-Dawley rats were randomly divided into AP (n=24) and normal (n=6) groups. Rats in the AP group received a retrograde injection of 5% sodium taurocholate into the biliary-pancreatic duct and then randomly assigned to untreated, emodin, combined emodin and ML385, and dexamethasone (DEX) groups. Pancreatic and pulmonary injury was assessed using H&E staining. In in vitro study, rat alveolar epithelial cell line L2 cells were exposed to lipopolysaccharide and treated with emodin. Nrf2 siRNA pool was applied for the knockdown of Nrf2. The contents of the pro-inflammatory cytokines in the bronchoalveolar lavage fluid and lung were determined using enzyme-linked immunosorbent assay. The expressions of related mRNAs and proteins in the lung or L2 cells were detected using real-time polymerase chain reaction, Western blot, immunohistochemistry and immunofluorescence. Key Findings: Emodin administration alleviated pancreatic and pulmonary injury of rats with AP. Emodin administration suppressed the production of proinflammatory cytokines, downregulated NLRP3, ASC and caspase-1 expressions and inhibited NF-κB nuclear accumulation in the lung. In addition, Emodin increased Nrf2 nuclear translocation and upregulated HO-1 expression. Moreover, the anti-inflammatory effect of emodin was blocked by Nrf2 inhibitor ML385. Conclusion: Emodin effectively protects rats against AP-associated lung injury by inhibiting NLRP3 inflammasome activation via Nrf2/HO-1 signaling.

Emodin Alleviates Severe Acute Pancreatitis-Associated Acute Lung Injury by Inhibiting the Cold-Inducible RNA-Binding Protein (CIRP)-Mediated Activation of the NLRP3/IL-1β/CXCL1 Signaling

“…Our novel data indicated that emodin ameliorated the severity of SAP-ALI by through inhibiting the CIRP-related signaling and decreased neutrophil infiltration in the lung of rats by attenuating the CIRP-induced IL-1β-dependent CXCL1 expression. A previous study has showed that emodin can relieve SAP-associated lung injury by inhibiting the activation of NLRP3 inflammasome (Gao et al, 2020). Our study also indicated that emodin reduced cell pyroptosis and IL-1β production as well as CXCL1 expression by inhibiting the activation of NLRP3 inflammasome induced by CIRP, which may be the key mechanism underlying the action of emodin in reducing SAP-ALI severity in rats.…”

Emodin ameliorates acute pancreatitis‑induced lung injury by suppressing NLRP3 inflammasome‑mediated neutrophil recruitment

“…A number of studies investigating the anti-inflammatory potential of emodin have also been reported (27,28). However, the functional involvement of emodin in neutrophil recruitment and IL-1β secretion through inflammasome regulation has not been reported in SAP-induced ALI in vivo (29). On the other hand, dexamethasone (DEX) is an important glucocorticoid that is vital in anti-inflammation and anti-toxicity, and can be used to alleviate early inflammatory reactions in the lungs in SAP (30).…”

“…Histopathological analysis. Histopathological analysis was performed in accordance with a previously published method (29). Briefly, tissue samples obtained from the right upper lobe and from the pancreas were fixed in 4% paraformaldehyde solution for 24 h at room temperature and then embedded in paraffin.…”

<p>Eldecalcitol Inhibits LPS-Induced NLRP3 Inflammasome-Dependent Pyroptosis in Human Gingival Fibroblasts by Activating the Nrf2/HO-1 Signaling Pathway</p>

“…Studies have found that the activation of Nrf2 and induction of HO-1 could inhibit the NLRP3 inflammasome and thus pyroptosis. [16][17][18] Activation of the Nrf2 pathway with isorhamnetin reduces the inflammatory response of HGFs. 19 These findings promote speculation that the activation of Nrf2/HO-1 may be a protection mechanism in periodontitis and reduce pyroptosis.…”