Protective effect of andrographolide against concanavalin A-induced liver injury

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.

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

Molecules ◽

10.3390/molecules24010028 ◽

2018 ◽

Vol 24 (1) ◽

pp. 28 ◽

Cited By ~ 3

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.

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

Journal of Pharmacy and Pharmacology ◽

10.1211/jpp/61.06.0009 ◽

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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Protective Effect of FTY720 on Several Markers of Liver Injury Induced by Concanavalin A in Mice

Current Therapeutic Research ◽

10.1016/j.curtheres.2012.07.001 ◽

2012 ◽

Vol 73 (4-5) ◽

pp. 140-149 ◽

Cited By ~ 4

Author(s):

Xiao-Dong Yin ◽

Pei-Jie Jia ◽

Yan Pang ◽

Jing-Hua He

Keyword(s):

Liver Injury ◽

Protective Effect ◽

Concanavalin A

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Protective effect of Yiguanjian decoction against DNA damage on concanavalin A-induced liver injury mice model

Journal of Traditional Chinese Medicine ◽

10.1016/s0254-6272(16)30064-4 ◽

2016 ◽

Vol 36 (4) ◽

pp. 471-478 ◽

Cited By ~ 5

Author(s):

Tian Mengxi ◽

Liu Wenlan ◽

You Hongjie ◽

Zhao Qingzhou ◽

Ouyang Luodan ◽

...

Keyword(s):

Dna Damage ◽

Liver Injury ◽

Protective Effect ◽

Concanavalin A ◽

Mice Model

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Mesenchymal Stem Cells-Derived Exosomes as Dexamethasone Delivery Vehicles for Autoimmune Hepatitis Therapy

Frontiers in Bioengineering and Biotechnology ◽

10.3389/fbioe.2021.650376 ◽

2021 ◽

Vol 9 ◽

Author(s):

Jiawei Zhao ◽

Yue Li ◽

Rongrong Jia ◽

Jinghui Wang ◽

Min Shi ◽

...

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Liver Injury ◽

Mouse Model ◽

Protective Effect ◽

Autoimmune Hepatitis ◽

Concanavalin A ◽

Drug Carrier ◽

Con A ◽

Delivery Vehicles

Exosomes (Exos) are nanosized vesicles (around 100 nm) that recently serve as a promising drug carrier with high biocompatibility and low immunogenicity. Previous studies showed that Exos secreted from mesenchymal stem cells (MSCs) provide protection for concanavalin A (Con A)-induced liver injury. In this study, the protective effect of Exos is confirmed, and dexamethasone (DEX)-incorporated Exos named Exo@DEX are prepared. It is then investigated whether Exo@DEX can function more efficiently compared to free drugs and naive Exos in a Con A-induced autoimmune hepatitis (AIH) mouse model. The results show that Exo@DEX efficiently improves the accumulation of DEX in AIH in the liver. These data suggest that Exo@DEX is a promising drug carrier for AIH and could have applications in other diseases.

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