Magnesium isoglycyrrhizinate ameliorates lipopolysaccharide-induced liver injury by upregulating autophagy and inhibiting inflammation via IL-22 expression.
Magnesium isoglycyrrhizinate ameliorates lipopolysaccharide-induced liver injury by upregulating autophagy and inhibiting inflammation via IL-22 expression.
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DOI：
10.1016/j.bioorg.2022.106034
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发表时间：
2022-07
影响因子：
5.1
通讯作者：
Xu Zhou;Xiao-ting Li;Kefan Yi;Chunhua Liang;Shan-shan Geng;Jian-yun Zhu;Chun-feng Xie;Cai-yun Zhong-Ca
中科院分区：
文献类型：
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作者：
Xu Zhou;Xiao-ting Li;Kefan Yi;Chunhua Liang;Shan-shan Geng;Jian-yun Zhu;Chun-feng Xie;Cai-yun Zhong-Ca
肝病已成为全球过早死亡的主要原因。众所周知，炎症反应失调在大多数肝脏疾病中起着至关重要的作用。异甘草酸镁（MgIG）是一种中草药，具有良好的保肝作用，已被临床用于治疗肝病。然而，MgIG在体内调节LPS诱导的肝损伤和炎症的机制仍不清楚。在我们的研究中，MgIG预处理通过调节巨噬细胞/中性粒细胞浸润抑制细胞凋亡和炎症减轻LPS诱导的肝损伤。MgIG可改善LPS对促氧化酶（NOX 1/2/4）和抗氧化酶（SOD 1/2）的影响。有趣的是，我们发现肝保护细胞因子白细胞介素（IL）-22的水平显着上调在MgIG处理的肝组织，这可能是一个潜在的机制，MgIG抗肝损伤。此外，MgIG处理不仅抑制了TLR 4/MyD 88/NF-κB信号通路，而且激活了自噬。IL-22激活自噬，抑制TLR 4/NF-κB信号通路，提示IL-22激活的自噬和炎症抑制也参与了MgIG的保护作用。总之，我们的研究结果揭示了MgIG的保肝作用的潜在机制，这为MgIG用于预防和治疗肝脏疾病提供了关键证据。
Liver disease has become a major cause of premature mortality worldwide. It is well known that dysregulated inflammation response plays a crucial role in most liver diseases. As a Chinese medicinal herb, Magnesium isoglycyrrhizinate (MgIG) has been proven to have good hepatoprotective activity and has been used in clinic to treat liver disease. However, the mechanisms by which MgIG regulates LPS-induced liver injury and inflammationin vivoremain elusive. In our study, MgIG pretreatment mitigated LPS-induced liver damage by suppressing apoptosis and inflammation via regulating macrophage/neutrophil infiltration. MgIG ameliorated the effects of LPS on pro-oxidant enzymes (NOX1/2/4) and anti-oxidant enzymes (SOD1/2). Interestingly, we found that the level of the hepatoprotective cytokine interleukin (IL)–22 was significantly upregulated in MgIG-treated liver tissues, which might be a potential mechanism of MgIG against liver injury. Moreover, we found that MgIG treatment not only inhibited TLR4/MyD88/NF-κB signaling pathway, but also activated autophagy. Furthermore, IL-22 treatment activated autophagy and inhibited TLR4/NF-κB signaling pathwayin vitro, suggesting that IL-22-activated autophagy and -inhibited inflammation also participated in the protective effects of MgIG. Altogether, our results uncovered the potential mechanisms of the hepatoprotective effects of MgIG, which provided critical evidence to support the use of MgIG to prevent and treat liver diseases.