AUTHOR=Wu Xiajia , Yao Jiaqi , Hu Qian , Kang Hongxin , Miao Yifan , Zhu Lv , Li Cong , Zhao Xianlin , Li Juan , Wan Meihua , Tang Wenfu 

TITLE=Emodin Ameliorates Acute Pancreatitis-Associated Lung Injury Through Inhibiting the Alveolar Macrophages Pyroptosis

JOURNAL=Frontiers in Pharmacology

VOLUME=13

YEAR=2022

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2022.873053

DOI=10.3389/fphar.2022.873053

ISSN=1663-9812

ABSTRACT=<p><bold>Objective:</bold> To investigate the protective effect of emodin in acute pancreatitis (AP)-associated lung injury and the underlying mechanisms.</p><p><bold>Methods:</bold> NaT-AP model in rats was constructed using 3.5% sodium taurocholate, and CER+LPS-AP model in mice was constructed using caerulein combined with Lipopolysaccharide. Animals were divided randomly into four groups: sham, AP, Ac-YVAD-CMK (caspase-1 specific inhibitor, AYC), and emodin groups. AP-associated lung injury was assessed with H&amp;E staining, inflammatory cytokine levels, and myeloperoxidase activity. Alveolar macrophages (AMs) pyroptosis was evaluated by flow cytometry. In bronchoalveolar lavage fluid, the levels of lactate dehydrogenase and inflammatory cytokines were measured by enzyme-linked immunosorbent assay. Pyroptosis-related protein expressions were detected by Western Blot.</p><p><bold>Results:</bold> Emodin, similar to the positive control AYC, significantly alleviated pancreas and lung damage in rats and mice. Additionally, emodin mitigated the pyroptotic process of AMs by decreasing the level of inflammatory cytokines and lactate dehydrogenase. More importantly, the protein expressions of NLRP3, ASC, Caspase1 p10, GSDMD, and GSDMD-NT in AMs were significantly downregulated after emodin intervention.</p><p><bold>Conclusion:</bold> Emodin has a therapeutic effect on AP-associated lung injury, which may result from the inhibition of NLRP3/Caspase1/GSDMD-mediated AMs pyroptosis signaling pathways.</p>