scholarly journals Salidroside Attenuates Concanavalin A-Induced Hepatitis via Modulating Cytokines Secretion and Lymphocyte Migration in Mice

2014 ◽  
Vol 2014 ◽  
pp. 1-11 ◽  
Author(s):  
Baoji Hu ◽  
Yun Zou ◽  
Shanshan Liu ◽  
Jun Wang ◽  
Jiali Zhu ◽  
...  
Keyword(s):  
Medicinal Plant ◽  
Protective Effect ◽  
T Lymphocyte ◽  
Concanavalin A ◽  
Control Group ◽  
Lymphocyte Migration ◽  
Con A ◽  
Immune Mediated ◽  
Liver Injuries ◽  
Cytokines Secretion

Salidroside, isolated from the medicinal plantRhodiola, was reported to serve as an “adaptogen.” This study was designed to explore the protective effect of salidroside on concanavalin A- (Con A-) induced hepatitis in mice and investigate potential mechanisms. C57BL/6 mice were randomly divided into control group, Con A group, and salidroside group. Salidroside (50 mg/kg) was injected intravenously followed by Con A administration. The levels of ALT, AST, inflammatory cytokines and CXCL-10 were examined. The pathological damage of livers was assessed, the amounts of phosphorylated IκBαand p65 were measured, and the numbers of CD4+and CD8+T lymphocytes in the blood, spleen and infiltrated in the liver were calculated. Our results showed that salidroside pretreatment reduced the levels of ALT, AST dramatically and suppressed the secretion of proinflammatory cytokines through downregulating the activity of NF-κB partly. Salidroside altered the distribution of CD4+and CD8+T lymphocyte in the liver and spleen through regulating CXCL-10 and decreased the severity of liver injuries. In conclusion, these results confirm the efficacy of salidroside in the prevention of immune mediated hepatitis in mice.

scholarly journals Corilagin Ameliorates Con A-Induced Hepatic Injury by Restricting M1 Macrophage Polarization

2022 ◽  
Vol 12 ◽  
Author(s):  
Fenglian Yan ◽  
Dalei Cheng ◽  
Haiyan Wang ◽  
Min Gao ◽  
Junfeng Zhang ◽  
...  
Keyword(s):  
Signaling Pathways ◽  
Hepatic Injury ◽  
Mononuclear Cells ◽  
Macrophage Polarization ◽  
Treatment Choice ◽  
Control Group ◽  
Con A ◽  
Immune Mediated ◽  
M1 Macrophage ◽  
Mitogen Activated Protein

Immune-mediated hepatic injury plays a key role in the initiation and pathogenesis of diverse liver diseases. However, treatment choice for immune-mediated hepatic injury remains limited. Corilagin, a natural ellagitannin extracted from various traditional Chinese medicines, has been demonstrated to exhibit multiple pharmacological activities, such as anti-inflammatory, anti-tumor, and hepatoprotective properties. The present study aimed to investigate the effects of corilagin on immune-mediated hepatic injury using a murine model of concanavalin A (Con A)-induced hepatitis, which is well-characterized to study acute immune-mediated hepatitis. Herein, mice were administered corilagin (25 mg/kg) intraperitoneally twice at 12 h intervals, and 1 h later, the mice were challenged with Con A (20 mg/kg body weight); serum and liver samples were collected after 12 h. The results showed that corilagin significantly increased the survival of mice and reduced serum alanine transaminase (ALT) and aspartate aminotransferase (AST) levels. In addition, corilagin markedly improved histopathological damage, hepatocyte apoptosis, and oxidative stress in the liver. The activation of M1 macrophages in the hepatic mononuclear cells was also significantly reduced compared with that in the control group. The expression of M1 macrophage-associated proinflammatory cytokines and genes, including interleukin (IL)-6, IL-12, and inducible nitric oxide synthase (iNOS), was also decreased after corilagin treatment. Finally, the results demonstrated that corilagin regulated macrophage polarization by modulating the mitogen-activated protein kinases (MAPK), nuclear factor (NF)-κB, and interferon regulatory factor (IRF) signaling pathways. Thus, the findings indicate that corilagin protects mice from Con A-induced immune-mediated hepatic injury by limiting M1 macrophage activation via the MAPK, NF-κB, and IRF signaling pathways, suggesting corilagin as a possible treatment choice for immune-mediated hepatic injury.

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 Glucosylceramide synthase regulates hepatocyte repair after concanavalin A-induced immune-mediated liver injury

PeerJ ◽  
2021 ◽  
Vol 9 ◽  
pp. e12138
Author(s):  
Jian Gan ◽  
Qin Gao ◽  
Li Li Wang ◽  
Ai Ping Tian ◽  
Long Dong Zhu ◽  
...  
Keyword(s):  
Liver Injury ◽  
Repair Process ◽  
Tissue Inhibitor Of Metalloproteinase ◽  
Control Group ◽  
Hepatocyte Apoptosis ◽  
Con A ◽  
Glucosylceramide Synthase ◽  
Qrt Pcr ◽  
Immune Mediated ◽  
Synthase Inhibitor

Background Sphingolipids produce pleiotropic signaling pathways, and participate in the pathological mechanism of hepatocyte apoptosis and necrosis during liver injury. However, the role of glucosylceramide synthase (GCS)–key enzyme that catalyzes the first glycosylation step, in liver injury is still vague. Methods All experiments were conducted using 7–9-week-old pathogen-free male C57BL/6 mice. Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels were detected in murine models of liver disease, in addition to histological characterization of liver injuries. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the relative expression of the GCS, matrix metallopeptidase-1 (MMP-1), and tissue inhibitor of metalloproteinase-1 (TIMP-1) genes. The GCS was observed through a fluorescence microscope, and the flow cytometry was used to detect hepatocyte apoptosis. The concentrations of serum IL-4, IL-6, and IL-10 were measured using enzyme-linked immune-sorbent assay (ELISA) kit. MMP-1 and TIMP-1 protein expression was measured via western blot (WB) analysis. Results Con A is often used as a mitogen to activate T lymphocytes and promote mitosis. A single dose of Con A injected intravenously will cause a rapid increase of ALT and AST, which is accompanied by the release of cytokines that cause injury and necrosis of hepatocytes. In this study, we successfully induced acute immune hepatitis in mice by Con A. Con A administration resulted in GCS upregulation in liver tissues. Moreover, the mice in the Con A group had significantly higher levels of ALT, AST, IL-4, IL-6, IL-10 and increased hepatocyte apoptosis than the control group. In contrast, all of the aforementioned genes were significantly downregulated after the administration of a GCS siRNA or Genz-123346 (i.e., a glucosylceramide synthase inhibitor) to inhibit the GCS gene. Additionally, the histopathological changes observed herein were consistent with our ALT, AST, IL-4, IL-6, and IL-10 expression results. However, unlike this, hepatocyte apoptosis has been further increased on the basis of the Con A group. Moreover, our qRT-PCR and WB results indicated that the expression of MMP-1 in the Con A group was significantly lower than that in the control group, whereas TIMP-1 exhibited the opposite trend. Conversely, MMP-1 expression in the GCS siRNA and Genz-123346 groups was higher than that in the Con A group, whereas TIMP-1 expression was lower. Conclusions GCS inhibition reduces Con A-induced immune-mediated liver injury in mice, which may be due to the involvement of GCS in the hepatocyte repair process after injury.

scholarly journals Gastroprotective Effects of Methanolic Leaves and Stem Extracts of Sphagneticola trilobata on Indomethacin-Induced Gastric Ulcer in Rats

2021 ◽  
Vol 34 (1) ◽  
pp. 111-117
Author(s):  
Kartik Singhal ◽  
Chandana Majee ◽  
Bhavani Pentela ◽  
Vikas Sharma
Keyword(s):  
Gastric Ulcer ◽  
South America ◽  
Medicinal Plant ◽  
Protective Effect ◽  
Folk Medicine ◽  
Gastric Ulcers ◽  
Control Group ◽  
Methanolic Extracts ◽  
Neutrophil Percentage ◽  
Stem Extract

The medicinal plant Sphagneticola trilobata native to South America is used in local folk medicine to treat inflammation and analgesics. In present study, gastroprotective effects of methanolic extracts of S. trilobata leaves and stem were investigated in indomethacin-induced gastric ulcers in rats at doses of 200 mg/kg for leave extract and 350 mg/kg for stem extract. Indomethacin produced stomach ulcers and increased neutrophil percentage and MDA levels compared to the control group (p < 0.001). Co-administration of indomethacin and omeprazole, methanolic extracts of leaves (200 mg/kg) (p < 0.001) and methanolic extracts (350 mg/kg) (p < 0.05) of stem compared to indomethacin group to ulcers was low (p < 0.001). Methanolic extracts (200 mg/kg) of leaves and methanolic extracts (350 mg/kg) of stem reduced MDA levels (p < 0.001). Methanolic extracts (200 mg/kg) of leaves and methanolic extracts (350 mg/kg) of the stem significantly decreased neutrophil percentage compared to indomethacin group (p < 0.001). The results suggest that the methanolic extracts of Sphagneticola trilobata leaves and stem have a protective effect on indomethacin-induced gastric ulcers.

scholarly journals Thymoquinone Attenuates Immune Mediated Liver Injury Induced by Concanavalin A in Mice

2021 ◽  
Vol 30 (2) ◽  
pp. 50-57
Author(s):  
Halla A. Ahmad ◽  
Sarmed H. Kathem
Keyword(s):  
Liver Injury ◽  
Inflammatory Cytokines ◽  
Liver Damage ◽  
Concanavalin A ◽  
Liver Tissue ◽  
Tissue Homogenate ◽  
Control Group ◽  
Dependent Manner ◽  
Immune Mediated ◽  
Dose Dependent

Autoimmune hepatitis is an inflammatory disease and its incidence has been increasing. The features of hepatitis are the release of inflammatory cytokines, the elevation of AST and ALT, and hepatocyte apoptosis and necrosis. Concanavalin A considered as essential model represents the acute immune-mediated liver damage in rodents. Thymoquinone is well known herbal compound that exert hepatoprotective, anti-inflammatory, and antioxidant activity. In this study, we focus on the immunoregulatory and liver protective effect of thymoquinone in a mouse model of concanavalin A-induced liver injury. Twenty-four male mice were randomly divided into four groups each containing six animals: Negative control group, concanavalin A model group, thymoquinone 15mg/kg group, and thymoquinone 30mg/kg group. Blood was collected to detect the activities of alanine transaminase (ALT) and aspartate transaminase (AST) as well as liver tissue for the detection of tumor necrosis factor  levels, after 8 hours of concanavalin A injection. Injecting mice with concanavalin resulted in a dramatic increase in serum level of both ALT and AST which indicate severe liver tissue damage with a significant increase in inflammatory cytokines TNF alpha - and INF  levels, with a notable increase in NF-kB gene expression in mice liver tissue homogenate. Thymoquinone pretreatment revealed a dose-dependent increase in liver tissue protection. Conclusion: Thymoquinone has hepatoprotective and immune modulatory effects in concanavalin A induced immune mediated liver damage. Thymoquinone exerted its effect through attenuating NF and its downstream effectors TNF  and INF  in a dose dependent manner.

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

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.

Hepatoprotective effects of early pentoxifylline administration on hepatic injury induced by concanavalin A in rat

2014 ◽  
Vol 92 (6) ◽  
pp. 490-497 ◽  
Author(s):  
Doaa Ibrahim Mohamed ◽  
Ahmed Abdel salam Mohamed Elmelegy ◽  
Lubna Foaad A. El-Aziz ◽  
Hala Salah Abdel kawy ◽  
Abeer Ahmed AbdEl-Samad ◽  
...  
Keyword(s):  
Body Mass ◽  
Concanavalin A ◽  
Hepatic Injury ◽  
Histopathological Examination ◽  
Smooth Muscle Actin ◽  
Portal Pressure ◽  
Control Group ◽  
Con A ◽  
Alpha Smooth Muscle Actin ◽  
Tnf Α

Tumor necrosis factor alpha (TNF-α) plays an important role in the pathogensis of hepatitis C virus (HCV) infection induced liver injury. This study aimed to evaluate the effects of TNF-α inhibition with pentoxifylline (PTX) on concanavalin A (Con A)-induced hepatic injury in rats. The rats were distributed among 3 groups: (i) control group (1 mL saline·week–1 by intravenous injection (i.v.)); (ii) Con A treatment group (20 mg Con A·(kg body mass)–1·week–1, i.v.), and (iii) rats treated with Con A and with PTX (200 mg PTX·(kg body mass)–1·day–1, per oral) group. Blood samples and livers were collected at the end of weeks 1, 2, 4, and 8 of Con A treatment. Portal pressure (PP) was measured at the end of week 8. The administration of PTX was found to confer significant protection against the injurious effects of Con A on the liver, by reducing serum levels of aspartate aminotransferase, alanine aminotransferase, hepatic TNF-α, and malondialdehyde. Histopathological examination revealed that treatment with PTX significantly suppressed early inflammation, reduced alpha smooth muscle actin, and the apoptosis of hepatocytes induced by Con A. Moreover, PTX significantly (P < 0.05) reduced PP, and quantitative analyses of the area of fibrosis induced by treatment with Con A showed a significant reduction at the end of week 8. We conclude that rats treated with PTX revealed a more or less normal hepatocyte architecture as well as marked improvement in fibrosis and PP.

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