Inhibition of P2X7R–NLRP3 Inflammasome Activation by Pleurotus citrinopileatus: A Possible Protective Role in Alcoholic Hepatosteatosis,Journal of Agricultural and Food Chemistry

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Inhibition of P2X7R–NLRP3 Inflammasome Activation by Pleurotus citrinopileatus: A Possible Protective Role in Alcoholic Hepatosteatosis
Journal of Agricultural and Food Chemistry ( IF 5.7 ) Pub Date : 2018-11-29 00:00:00 , DOI: 10.1021/acs.jafc.8b05756
Xia Li ₁ , Quan Jin ₁ , Yu Zhang ₁ , Yan-Ling Wu ₁ , Cheng-Min Jin ₂ , Ben-Wen Cui ₁ , Ying Li ₁ , Ming-Ji Jin ₁ , Yue Shang ₁ , Min Jiang ₁ , Hong-Xu Yang ₁ , Mei Wu ₁ , Jian Liu ₁ , Li-Hua Lian ₁ , Ji-Xing Nan _{1,

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Affiliation

Pleurotus citrinopileatus (golden oyster mushroom) is a widely used edible mushroom. We investigated the inhibitory effect of P. citrinopileatus aqueous extract against alcoholic steatohepatitis and its underlying mechanism. Acute and chronic ethanol-feeding murine models were established by intragastrically administering ethanol or feeding an ethanol-containing Lieber–DeCarli liquid diet to male C57BL/6 mice. In both models, P. citrinopileatus decreased serum alanine aminotransferase (ALT), aspartate transaminase (AST), triglyceride (TG), and hepatic TG levels. Hematoxylin and eosin (HE) and Oil Red O staining confirmed that P. citrinopileatus ameliorated both acute and chronic alcoholic hepatosteatosis, characterized by regulation of lipid-metabolism-related proteins, including sirtuin 1 (SIRT1), AMP-activated kinase (AMPK), and sterol regulatory element-binding protein (SREBP1). P. citrinopileatus reversed inflammatory response via modulating purinergic receptor P2X ligand-gated ion channel 7 (P2X7R)-NOD-like receptor pyrin domain 3 (NLRP3) inflammasome. P. citrinopileatus restored the expressions of those proteins to a normal level. In addition, HepG2 cells were incubated with P. citrinopileatus prior to ethanol stimulation. P. citrinopileatus reduced ethanol exposure-induced lipid deposition. Concomitantly, P. citrinopileatus increased AMPK and SIRT1 expressions, which were reduced by ethanol treatment. P. citrinopileatus ameliorated alcoholic hepatic steatosis and accompanied inflammatory response via regulating SIRT1–AMPK and P2X7R–NLRP3 inflammasome activation, highlighting a promising strategy and utility of P. citrinopileatus for alcoholic steatohepatitis as dietary health supplements.

中文翻译：

P2X7R-NLRP3炎性激活的抑制通过金顶：在酒精Hepatosteatosis一种可能保护作用

杏鲍菇（金菇菇）是一种广泛使用的食用菌。我们调查了P. citrinopileatus水提取物对酒精性脂肪性肝炎的抑制作用及其潜在机制。通过向胃内施用乙醇或向雄性C57BL / 6小鼠饲喂含乙醇的Lieber-DeCarli流质饮食，建立了急性和慢性饲喂乙醇的小鼠模型。在这两种模型中，柑桔疟原虫都降低了血清丙氨酸转氨酶（ALT），天冬氨酸转氨酶（AST），甘油三酸酯（TG）和肝TG的水平。苏木精和曙红（HE）以及油红O染色证实了柑桔青霉改善了急性和慢性酒精性肝脂肪变性，其特点是调节与脂质代谢相关的蛋白质，包括瑟土因1（SIRT1），AMP激活激酶（AMPK）和固醇调节元件结合蛋白（SREBP1）。P.黄蘑颠倒通过调节嘌呤受体P2X配体门控离子通道7（P2X7R）-NOD样受体热蛋白结构域3（NLRP3）炎性炎症反应。柠檬青枯菌使那些蛋白质的表达恢复到正常水平。另外，在乙醇刺激之前，将HepG2细胞与柠檬青假单胞菌一起孵育。柑桔疟原虫减少了乙醇暴露诱导的脂质沉积。与此同时，P.榆黄蘑增加了AMPK和SIRT1的表达，而乙醇处理则降低了这些表达。P.黄蘑改善酒精性脂肪肝并伴有通过调节SIRT1-AMPK和P2X7R-NLRP3炎性小体活化，突出的有前途的策略和效用炎症反应P.黄蘑为酒精性脂肪性肝炎膳食保健品。

更新日期：2018-11-29

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