scholarly journals Emodin Attenuates Lipopolysaccharide-Induced Acute Liver Injury via Inhibiting the TLR4 Signaling Pathway in vitro and in vivo

2018 ◽  
Vol 9 ◽  
Author(s):  
Yan Ding ◽  
Pan Liu ◽  
Zhi-Lin Chen ◽  
Shao-Jun Zhang ◽  
You-Qin Wang ◽  
...  
Keyword(s):  
Liver Injury ◽  
Signaling Pathway ◽  
Acute Liver Injury ◽  
Tlr4 Signaling ◽  
Tlr4 Signaling Pathway

scholarly journals Mechanism of KLF4 Protection against Acute Liver Injury via Inhibition of Apelin Signaling

2019 ◽  
Vol 2019 ◽  
pp. 1-10 ◽  
Author(s):  
Weitao Ji ◽  
Hongyun Shi ◽  
Hailin Shen ◽  
Jing Kong ◽  
Jiayi Song ◽  
...  
Keyword(s):  
Liver Injury ◽  
Signaling Pathway ◽  
Acute Liver Injury ◽  
Control Group ◽  
Necrosis Factor Alpha ◽  
Protein Levels ◽  
Klf4 Expression ◽  
Mrna And Protein Expression

Krüppel-like factor 4 (KLF4) is a key transcription factor that regulates genes involved in the proliferation or differentiation in different tissues. Apelin plays roles in cardiovascular functions, metabolic disease, and homeostatic disorder. However, the biological function of apelin in liver disease is still ongoing. In this study, we investigated the mechanism of KLF4-mediated protection against acute liver injury via the inhibition of the apelin signaling pathway. Mice were intraperitoneally injected with carbon tetrachloride (CCl4; 0.2 mL dissolved in 100 mL olive oil, 10 mL/kg) to establish an acute liver injury model. A KLF4 expression plasmid was injected through the tail vein 48 h before CCl4 treatment. In cultured LX-2 cells, pAd-KLF4 or siRNA KLF4 was overexpressed or knockdown, and the mRNA and protein levels of apelin were determined. The results showed that the apelin serum level in the CCl4-injected group was higher than that of control group, and the expression of apelin in the liver tissues was elevated while KLF4 expression was decreased in the CCl4-injected group compared to the KLF4-plasmid-injected group. HE staining revealed serious hepatocellular steatosis in the CCl4-injected mice, and KLF4 alleviated this steatosis in the mice injected with KLF4 plasmid. In vitro experiments showed that tumor necrosis factor-alpha (TNF-α) could downregulate the transcription and translation levels of apelin in LX-2 cells and also upregulate KLF4 mRNA and protein expression. RT-PCR and Western blotting showed that the overexpression of KLF4 markedly decreased basal apelin expression, but knockdown of KLF4 restored apelin expression in TNF-α-treated LX-2 cells. These in vivo and in vitro experiments suggest that KLF4 plays a key role in inhibiting hepatocellular steatosis in acute liver injury, and that its mechanism might be the inhibition of the apelin signaling pathway.

Salvianolic acid B exerts a protective effect in acute liver injury by regulating the Nrf2/HO-1 signaling pathway

2020 ◽  
Vol 98 (3) ◽  
pp. 162-168 ◽  
Author(s):  
Yong-mei Jin ◽  
Xiang-ming Tao ◽  
Yi-ning Shi ◽  
Youjin Lu ◽  
Jin-yu Mei
Keyword(s):  
Liver Injury ◽  
Signaling Pathway ◽  
Acute Liver Injury ◽  
Damage Model ◽  
Underlying Mechanism ◽  
Salvianolic Acid B ◽  
Salvianolic Acid ◽  
Injury Model

Salvianolic acid B (Sal B) exerts strong antioxidant activity and eliminates the free radical effect. However, how it affects the antioxidant pathway is not very clear. The objective of this study was to investigate the underlying mechanism of Sal B in CCl4-induced acute liver injury, especially its effect on the Nrf2/HO-1 signaling pathway. For the in vivo experiment, an acute liver injury model was induced using CCl4 and treated with Sal B. For the in vitro experiment, an oxidative damage model was established followed by Sal B treatment. Serum biochemical indicators and reactive oxygen species activity were detected using corresponding kits. Oxidant/antioxidant status was determined based on the levels of malondialdehyde, glutathione, and superoxide dismutase. Nrf2 and HO-1 levels were analyzed by Western blotting and immunohistochemical staining. Sal B treatment improved liver histology, decreased the aminotransferase levels, and attenuated oxidative stress in the acute liver injury model. Nrf2 and HO-1 levels were increased both in vivo and in vitro. Sal B suppresses acute liver injury and Nrf2/HO-1 signaling plays a key role in this process.

Dendrobium officinale polysaccharides protected against ethanol-induced acute liver injury in vivo and in vitro via the TLR4/NF-κB signaling pathway

Cytokine ◽  
2020 ◽  
Vol 130 ◽  
pp. 155058 ◽  
Author(s):  
Ke Yang ◽  
Lianghui Zhan ◽  
Tingting Lu ◽  
Cong Zhou ◽  
Xue Chen ◽  
...  
Keyword(s):  
Liver Injury ◽  
Signaling Pathway ◽  
Acute Liver Injury ◽  
Dendrobium Officinale

scholarly journals SDF-1/CXCR4 Augments the Therapeutic Effect of Bone Marrow Mesenchymal Stem Cells in the Treatment of Lipopolysaccharide-Induced Liver Injury by Promoting Their Migration Through PI3K/Akt Signaling Pathway

2020 ◽  
Vol 29 ◽  
pp. 096368972092999 ◽  
Author(s):  
Guanghui Xiu ◽  
Xiuling Li ◽  
Yunyu Yin ◽  
Jintao Li ◽  
Bingqin Li ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Liver Injury ◽  
Signaling Pathway ◽  
Therapeutic Effect ◽  
Acute Liver Injury ◽  
Akt Signaling ◽  
Akt Signaling Pathway

Mesenchymal stem cells (MSCs) are thought to have great potential in the therapy of acute liver injury. It is possible that these cells may be regulated by the stromal cell-derived factor-1 (SDF-1)/CXC chemokine receptor-4 (CXCR4) signaling axis, which has been shown to promote stem cells migration in the inflammation-associated diseases. However, the effects of SDF-1/CXCR4 axis on the MSCs-transplantation-based treatment for acute liver injury and the underlying mechanisms are largely unknown. In this study, we sought to determine whether SDF-1/CXCR4 would augment the therapeutic effect of bone marrow mesenchymal stem cells (BMSCs) by promoting their migration, which may result from activating the phosphoinositide 3-kinase (PI3K)/Akt signaling pathway, in a rat acute liver injury model induced by lipopolysaccharide (LPS). We found that BMSCs transplantation markedly attenuated liver injury and improved the survival of LPS-treated rats. Of interest, overexpression of CXCR4 in BMSCs could substantially promote their migration both in vitro and in vivo, and result in even better therapeutic effects. This might be attributed to the activation of PI3K/Akt signaling pathway in BMSCs that is downstream of CXCR4, as demonstrated by the use of the CXCR4 antagonist AMD3100 and PI3K pathway inhibitor LY294002 assays in vitro and in vivo. Together, our results unraveled a novel molecular mechanism for the therapeutic effect of BMSCs for the treatment of acute liver injury, which may shed a new light on the clinical application of BMSCs for acute liver failure.

scholarly journals 5-O-Demethylnobiletin Alleviates CCl4-Induced Acute Liver Injury by Equilibrating ROS-Mediated Apoptosis and Autophagy Induction

2021 ◽  
Vol 22 (3) ◽  
pp. 1083
Author(s):  
Sukkum Ngullie Chang ◽  
Se Ho Kim ◽  
Debasish Kumar Dey ◽  
Seon Min Park ◽  
Omaima Nasif ◽  
...  
Keyword(s):  
Liver Injury ◽  
Acute Liver Injury ◽  
Elevated Serum ◽  
In Vitro Study ◽  
Biological Properties ◽  
Autophagic Flux ◽  
Serum Aminotransferase ◽  
Ccl4 Treatment

Polymethoxyflavanoids (PMFs) have exhibited a vast array of therapeutic biological properties. 5-O-Demethylnobiletin (5-DN) is one such PMF having anti-inflammatory activity, yet its role in hepatoprotection has not been studied before. Results from in vitro study revealed that 5-DN did not exert a high level of cytotoxicity on HepG2 cells at 40 μM, and it was able to rescue HepG2 cell death induced by carbon tetrachloride (CCl4). Subsequently, we investigated acute liver injury on BALB/c mice induced by CCl4 through the intraperitoneal injection of 1 mL/kg CCl4 and co-administration of 5-DN at (1 and 2 mg/kg) by oral gavage for 15 days. The results illustrated that treatment with 5-DN attenuated CCl4-induced elevated serum aminotransferase (AST)/alanine aminotransferase (ALT) ratio and significantly ameliorated severe hepatic damage such as inflammation and fibrosis evidenced through lesser aberrations in the liver histology of 5-DN dose groups. Additionally, 5-DN efficiently counteracted and equilibrated the production of ROS accelerated by CCl4 and dramatically downregulated the expression of CYP2E1 vitally involved in converting CCl4 to toxic free radicals and also enhanced the antioxidant enzymes. 5-DN treatment also inhibited cell proliferation and inflammatory pathway abnormally regulated by CCl4 treatment. Furthermore, the apoptotic response induced by CCl4 treatment was remarkably reduced by enhanced Bcl-2 expression and noticeable reduction in Bax, Bid, cleaved caspase 3, caspase 9, and apaf-1 expression. 5-DN treatment also induced the conversion of LC3 and promoted the autophagic flux. Conclusively, 5-DN exhibited hepatoprotective effects in vitro and in vivo and prevented liver fibrosis induced by CCl4.

Ginsenoside Rg1 protects against acetaminophen-induced liver injury via activating Nrf2 signaling pathway in vivo and in vitro

2018 ◽  
Vol 98 ◽  
pp. 58-68 ◽  
Author(s):  
Chenqing Ning ◽  
Xiaoguang Gao ◽  
Changyuan Wang ◽  
Yulong Kong ◽  
Zhihao Liu ◽  
...  
Keyword(s):  
Liver Injury ◽  
Signaling Pathway ◽  
Ginsenoside Rg1 ◽  
Nrf2 Signaling Pathway

Guavinoside B from Psidium guajava alleviates acetaminophen-induced liver injury via regulating the Nrf2 and JNK signaling pathways

2020 ◽  
Vol 11 (9) ◽  
pp. 8297-8308
Author(s):  
Yuanyuan Li ◽  
Jialin Xu ◽  
Dongli Li ◽  
Hang Ma ◽  
Yu Mu ◽  
...  
Keyword(s):  
Liver Injury ◽  
Signaling Pathways ◽  
Signaling Pathway ◽  
Phenolic Compound ◽  
Psidium Guajava ◽  
Jnk Signaling ◽  
Nrf2 Signaling Pathway ◽  
Jnk Signaling Pathway

GUB, a main phenolic compound present in guava fruits, could alleviate APAP-induced liver injury in vitro and in vivo by activating the Nrf2 signaling pathway and inhibiting the JNK signaling pathway.

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.

Torularhodin Ameliorates Oxidative Activity in Vitro and d-Galactose-Induced Liver Injury via the Nrf2/HO-1 Signaling Pathway in Vivo

2019 ◽  
Vol 67 (36) ◽  
pp. 10059-10068 ◽  
Author(s):  
Chang Liu ◽  
Yan Cui ◽  
Fuwei Pi ◽  
Yahui Guo ◽  
Yuliang Cheng ◽  
...  
Keyword(s):  
Liver Injury ◽  
Signaling Pathway ◽  
Oxidative Activity
Sign in / Sign up

Export Citation Format

Share Document