scholarly journals Magnesium Isoglycyrrhizinate Ameliorates Concanavalin A-Induced Liver Injury by Inhibiting Autophagy

2022 ◽  
Vol 12 ◽  
Author(s):  
Zihao Fan ◽  
Yuxian Li ◽  
Sisi Chen ◽  
Ling Xu ◽  
Yuan Tian ◽  
...  
Keyword(s):  
Liver Injury ◽  
Protective Effect ◽  
Concanavalin A ◽  
Severe Liver ◽  
Cytokine Levels ◽  
Therapeutic Mechanism ◽  
Severe Liver Dysfunction ◽  
Hepatocyte Death ◽  
Magnesium Isoglycyrrhizinate

Background and Aims: Acute liver failure (ALF) is a type of liver injury that is caused by multiple factors and leads to severe liver dysfunction; however, current treatments for ALF are insufficient. Magnesium isoglycyrrhizinate (MgIG), a novel glycyrrhizin extracted from the traditional Chinese medicine licorice, has a significant protective effect against concanavalin A (ConA)-induced liver injury, but its underlying therapeutic mechanism is unclear. Hence, this study aims to explore the potential therapeutic mechanism of MgIG against ConA-induced immune liver injury.Methods: ConA (20 mg/kg, i. v.) was administered for 12 h to construct an immune liver injury model, and the treatment group was given MgIG (30 mg/kg, i. p.) injection 1 h in advance. Lethality, liver injury, cytokine levels, and hepatocyte death were evaluated. The level of autophagy was evaluated by electron microscopy, RT-PCR and western blotting, and hepatocyte death was assessed in vitro by flow cytometry.Results: MgIG significantly increased the survival rate of mice and ameliorated severe liver injury mediated by ConA. The decrease in the number of autophagosomes, downregulation of LC3b expression and upregulation of p62 expression indicated that MgIG significantly inhibited ConA-induced autophagy in the liver. Reactivation of autophagy by rapamycin (RAPA) reversed the protective effect of MgIG against ConA-induced liver injury. Compared with MgIG treatment, activation of autophagy by RAPA also promoted the expression of liver inflammation markers (IL-1β, IL-6, TNF-α, CXCL-1, CXCL-2, CXCL-10, etc.) and hepatocyte death. In vitro experiments also showed that MgIG reduced ConA-induced hepatocyte death but did not decrease hepatocyte apoptosis by inhibiting autophagy.Conclusion: MgIG significantly ameliorated ConA-induced immune liver injury in mice by inhibiting autophagy. This study provides theoretical support for the ability of MgIG to protect against liver injury in clinical practice.

The Matrine Derivate MASM Inhibits Recruitment of Gr1hi Monocyte and Alleviates Liver Injury

Pharmacology ◽  
2019 ◽  
Vol 104 (5-6) ◽  
pp. 235-243 ◽  
Author(s):  
Wei-Heng Xu ◽  
Jing Xu ◽  
Fang-Yuan Xie ◽  
Ying-Hua Li ◽  
Zhen-Lin Hu ◽  
...  
Keyword(s):  
Liver Injury ◽  
Protective Effect ◽  
Protective Role ◽  
Chronic Liver ◽  
Monocyte Chemoattractant Protein 1 ◽  
Nonparenchymal Cells ◽  
Hepatic Expression ◽  
Injury Models ◽  
Vitro Effect

Backgrounds: (6aS, 10S, 11aR, 11bR, 11cS)-10-methylaminododecahydro-3a, 7a-diaza-benzo (de) anthracene-8-thione (MASM), a novel derivative of matrine, exhibits better anti-inflammatory activity. This study was designed to evaluate the protective effect of MASM on acute and chronic liver injuries and explore the possible mechanisms. Methods: Acute and chronic liver injury models were established by the CCl4 intraperitoneal injection and the protective effect of MASM was assessed by biochemical and histological examination. The infiltration of different monocyte subsets into the liver was characterized and analyzed by flow cytometry. The in vitro effect of MASM on liver nonparenchymal cells was evaluated by real-time PCR and transwell chemotaxis assays. Results: Administration of MASM markedly attenuated acute liver injury and liver fibrosis induced by CCl4 injection. Meanwhile, the infiltrations of Gr1hi monocytes in injured livers and induced hepatic expression of monocyte chemoattractant protein-1 (MCP-1) were greatly inhibited. Cellular experiments demonstrated that MASM not only decreased the expression of MCP-1 but also inhibited its chemotactic activity. Conclusions: This study demonstrates that the protective effect of MASM on liver injury could be contributed to the suppression of Gr1hi monocyte infiltration to the liver and the inhibition of MCP-1 production and activity. These findings provide new insights into the protective role of MASM in liver injury.

Protective effect of pterostilbene on concanavalin A-induced acute liver injury

2019 ◽  
Vol 10 (11) ◽  
pp. 7308-7314 ◽  
Author(s):  
Jiayan Wu ◽  
Mengmeng Li ◽  
Jingwen He ◽  
Ke Lv ◽  
Meiyan Wang ◽  
...  
Keyword(s):  
Liver Injury ◽  
Protective Effect ◽  
Concanavalin A ◽  
Acute Liver Injury ◽  
Anti Inflammatory

Pterostilbene (PTE) is broadly found in berries and has antioxidant and anti-inflammatory properties.

scholarly journals Protective Effect of Eckol against Acute Hepatic Injury Induced by Carbon Tetrachloride in Mice

Marine Drugs ◽  
2018 ◽  
Vol 16 (9) ◽  
pp. 300 ◽  
Author(s):  
Shulan Li ◽  
Juan Liu ◽  
Mengya Zhang ◽  
Yuan Chen ◽  
Tianxing Zhu ◽  
...  
Keyword(s):  
Carbon Tetrachloride ◽  
Liver Injury ◽  
Protective Effect ◽  
Acute Liver Injury ◽  
Treated Group ◽  
Terminal Deoxynucleotidyl Transferase ◽  
Enhanced Expression ◽  
Pre Treatment

Several in vitro studies have shown the potential hepatoprotective properties of eckol, a natural phlorotannin derived from the brown alga. However, the in vivo hepatoprotective potential of eckol has not been determined. In this study, we performed an in vivo study to investigate the protective effect of eckol and its possible mechanisms on the carbon tetrachloride (CCl4)-induced acute liver injury model in mice. Results revealed that eckol pre-treatment at the dose of 0.5 and 1.0 mg/kg/day for 7 days significantly suppressed the CCl4-induced increases of alanine transaminase (ALT) and aspartate aminotransferase (AST) levels in serum and meliorated morphological liver injury. Terminal deoxynucleotidyl transferase-mediated dUTP nick end labelling (TUNEL) analysis showed that the number of positive apoptotic hepatocytes in the eckol-treated group was lower than that in the CCl4 model group. Western blotting analysis also demonstrated the enhanced expression of bcl-2 and suppressed expression of cleaved caspase-3 by eckol. The CCl4-induced oxidative stress in liver was significantly ameliorated by eckol, which was characterized by reduced malondialdehyde (MDA) formations, and enhanced superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) activities and glutathione (GSH) content. Moreover, the CCl4-induced elevations of pro-inflammatory cytokines tumor necrosis factor (TNF)-α, interleukin (IL)-1β and IL-6 were markedly suppressed in the eckol-treated group. However, eckol enhanced the level of IL-10, a potent anti-inflammatory cytokine, and recruited CD11c+ dendritic cells into the liver tissues of CCl4-treated mice. These results indicated that eckol has the protective effect on CCl4-induced acute liver injury via multiple mechanisms including anti-apoptosis, anti-oxidation, anti-inflammation and immune regulation.

Magnesium isoglycyrrhizinate ameliorates concanavalin A-induced liver injury via the p38 and JNK MAPK pathway

2020 ◽  
Vol 42 (5) ◽  
pp. 445-455
Author(s):  
Yudi Gao ◽  
Yuan Tian ◽  
Xiangying Zhang ◽  
Xiaohui Zhang ◽  
Zhongping Duan ◽  
...  
Keyword(s):  
Liver Injury ◽  
Concanavalin A ◽  
Mapk Pathway ◽  
Magnesium Isoglycyrrhizinate

scholarly journals The Protective Effect of Sheep Placental Extract on Concanavalin A-induced Liver Injury in Mice

Molecules ◽  
2018 ◽  
Vol 24 (1) ◽  
pp. 28 ◽  
Author(s):  
Jingwen Liu ◽  
Suting Luo ◽  
Jun Yang ◽  
Fazheng Ren ◽  
Yu Zhao ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Amino Acids ◽  
Liver Injury ◽  
Protective Effect ◽  
Concanavalin A ◽  
B Cell Lymphoma ◽  
Therapeutic Effects ◽  
Model Group ◽  
Con A ◽  
Placental Extract

Though the biological effects of human placental extract have been widely studied, it has limited availability and its use poses ethical problems. Thus, domestic animal placental extracts are suggested as alternatives. In this study, the protective effect of sheep placental extract (SPE) on concanavalin A (Con A)-induced liver injury was investigated. BALB/c mice were randomly divided into six groups, including one normal group and five experimental groups, which received different oral doses of SPE (0, 5, 10 and 50 mg/kg) or a mixture of amino acids for 3 days before Con A injection. Compared with Con A-induced model group, the SPE administration significantly decreased serum aminotransaminase activity, alleviated pathological changes, recovered liver antioxidant capacity and prevented the increase of nitric oxide. Secretion of pro-inflammatory cytokines in serum decreased and mRNA expression of hepatic intercellular adhesion molecule-1, interferon-inducible chemokine 10 and inducible nitric oxide synthase were downregulated, while B-cell lymphoma-2 expression increased. The administration of amino acids mixture had no significant effect in most measurements compared with the model group, which indicated proteins and peptides, rather than individual amino acid, were largely responsible for the bioactivity of SPE. The results indicate SPE has potential therapeutic effects against immune-mediated hepatitis.

scholarly journals Hepatocyte-Derived Igκ Exerts a Protective Effect against ConA-Induced Acute Liver Injury

2020 ◽  
Vol 21 (24) ◽  
pp. 9379
Author(s):  
Sha Yin ◽  
Qianwen Shi ◽  
Wenwei Shao ◽  
Chi Zhang ◽  
Yixiao Zhang ◽  
...  
Keyword(s):  
Liver Injury ◽  
Protective Effect ◽  
Caspase 3 ◽  
Normal Liver ◽  
Primary Hepatocytes ◽  
Normal Liver Cell ◽  
Serum Aspartate Aminotransferase ◽  
Mitochondrial Death Pathway ◽  
Cytoskeleton Dynamics

Immunoglobulin (Igκ) has been reported to be expressed in sorted liver epithelial cells of μMT mice, and the sequence characteristics of hepatocyte-derived Igκ were different from those of classical B-cell-derived Igκ. However, the physiological function of hepatocyte-derived Igκ is still unclear. The expression of Igκ was firstly identified in primary hepatocytes and normal liver cell line (NCTC1469), and hepatocyte-derived Igκ expression was elevated and displayed unique localization in hepatocytes of concanavalin A (ConA)-induced hepatitis model. Moreover, Igκ knockout mice were more sensitive to ConA-induced hepatitis and had higher serum aspartate aminotransferase (AST) levels, more severe histological injury and a greater number of terminal deoxynucleotide transferase-mediated deoxyuridine triphosphate nick end-labeling (TUNEL)-positive cells as compared with littermate controls. Furthermore, knockdown of Igκ in primary hepatocytes and NCTC1469 cells led to accelerated activation of the mitochondrial death pathway and caspase-3 cleavage in vitro, which might be related to inhibition of NF-κB signaling pathway and activation of JNK via the cytoskeleton dynamics. Taken together, these results indicate that hepatocyte-derived Igκ mediates cellular resistance to ConA-induced liver injury by inhibiting activation of caspase-3 and the mitochondrial death pathway, suggesting that Igκ plays an important role in hepatocyte survival and exerts a protective effect against ConA-induced liver injury in mice.

scholarly journals Yi-Qi-Jian-Pi Formula Suppresses RIPK1/RIPK3-Complex-Dependent Necroptosis of Hepatocytes Through ROS Signaling and Attenuates Liver Injury in Vivo and in Vitro

2021 ◽  
Vol 12 ◽  
Author(s):  
Feixia Wang ◽  
Li Tang ◽  
Baoyu Liang ◽  
Chun Jin ◽  
Liyuan Gao ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Liver Injury ◽  
Protective Effect ◽  
Molecular Mechanisms ◽  
Positive Role ◽  
Interacting Protein ◽  
Ros Signaling ◽  
Tnf Α

Acute-on-chronic liver failure (ACLF) is described as a characteristic of acute jaundice and coagulation dysfunction. Effective treatments for ACLF are unavailable and hence are urgently required. We aimed to define the effect of Yi-Qi-Jian-Pi Formula (YQJPF) on liver injury and further examine the molecular mechanisms. In this study, we established CCl4-, LPS-, and d-galactosamine (D-Gal)-induced ACLF rat models in vivo and LPS- and D-Gal-induced hepatocyte injury models in vitro. We found that YQJPF significantly ameliorates liver injury in vivo and in vitro that is associated with the regulation of hepatocyte necroptosis. Specifically, YQJPF decreased expression of receptor-interacting protein kinase 1 (RIPK1), receptor-interacting protein kinase 3 (RIPK3) and pseudokinase mixed lineage kinase domain-like (MLKL) to inhibit the migration of RIPK1 and RIPK3 into necrosome. YQJPF also reduces the expression of inflammatory cytokines IL-6, IL-8, IL-1β, and TNF-α, which were regulated by RIPK3 mediates cell death. RIPK1 depletion was found to enhance the protective effect of YQJPF. Furthermore, we showed that YQJPF significantly downregulates the mitochondrial reactive oxygen species (ROS) production and mitochondrial depolarization, with ROS scavenger, 4-hydroxy-TEMPO treatment recovering impaired RIPK1-mediated necroptosis and reducing the expression of IL-6, IL-8, IL-1β, and TNF-α. In summary, our study revealed the molecular mechanism of protective effect of YQJPF on hepatocyte necroptosis, targeting RIPK1/RIPK3-complex-dependent necroptosis via ROS signaling. Overall, our results provided a novel perspective to indicate the positive role of YQJPF in ACLF.

Protective effect of JBP485 on concanavalin A-induced liver injury in mice

2009 ◽  
Vol 61 (6) ◽  
pp. 767-774
Author(s):  
Tao Yang ◽  
Jingjing Wu ◽  
Changyuan Wang ◽  
Qi Liu ◽  
Xiaochi Ma ◽  
...  
Keyword(s):  
Liver Injury ◽  
Protective Effect ◽  
Concanavalin A
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