scholarly journals Dietary luteolin attenuates chronic liver injury induced by mercuric chloride via the Nrf2/NF-κB/P53 signaling pathway in rats

Oncotarget ◽  
2017 ◽  
Vol 8 (25) ◽  
pp. 40982-40993 ◽  
Author(s):  
Haili Zhang ◽  
Xiao Tan ◽  
Daqian Yang ◽  
Jingjing Lu ◽  
Biying Liu ◽  
...  
Keyword(s):  
Liver Injury ◽  
Signaling Pathway ◽  
Mercuric Chloride ◽  
Chronic Liver ◽  
Chronic Liver Injury ◽  
P53 Signaling ◽  
P53 Signaling Pathway

scholarly journals Aronia melanocarpa Prevents Alcohol-Induced Chronic Liver Injury via Regulation of Nrf2 Signaling in C57BL/6 Mice

2020 ◽  
Vol 2020 ◽  
pp. 1-13
Author(s):  
Zhuqian Wang ◽  
Yange Liu ◽  
Xuyu Zhao ◽  
Shuyan Liu ◽  
Yang Liu ◽  
...  
Keyword(s):  
Liver Injury ◽  
Signaling Pathway ◽  
Antioxidant Activities ◽  
Organ Damage ◽  
Chronic Liver ◽  
Related Factor ◽  
Chronic Liver Injury ◽  
Aronia Melanocarpa ◽  
Nrf2 Signaling Pathway ◽  
Cytokine Levels

Aronia melanocarpa (AM), which is rich in anthocyanins and procyanidins, has been reported to exert antioxidative and anti-inflammatory effects. This study aimed to systematically analyze the components of AM and explore its effects on alcohol-induced chronic liver injury in mice. A component analysis of AM revealed 17 types of fatty acids, 17 types of amino acids, 8 types of minerals, and 3 types of nucleotides. Chronic alcohol-induced liver injury was established in mice via gradient alcohol feeding over a period of 6 months, with test groups orally receiving AM in the last 6 weeks. AM administration yielded potential hepatoprotective effects by alleviating weight gain and changes in organ indexes, decreasing the ratio of alanine aminotransferase/aspartate aminotransferase, reducing lipid peroxidation, enhancing antioxidant activities, decreasing oxidation-related factor levels, and regulating inflammatory cytokine levels. Histological analyses suggest that AM treatment markedly prevented organ damage in alcohol-exposed mice. Furthermore, AM activated nuclear factor erythroid 2-like 2 (Nrf2) by downregulating the expression of Kelch-like ECH-associated protein 1, resulting in elevated downstream antioxidative enzyme levels. AM activated Nrf2 via modulation of the phosphatidylinositol-3-hydroxykinase/protein kinase B signaling pathway. Altogether, AM prevented alcohol-induced liver injury, potentially by suppressing oxidative stress via the Nrf2 signaling pathway.

scholarly journals Pterostilbene Alleviates Cholestasis by Promoting SIRT1 Activity in Hepatocytes and Macrophages

2021 ◽  
Vol 12 ◽  
Author(s):  
Chuanrui Ma ◽  
Jiaqing Xiang ◽  
Guixiao Huang ◽  
Yaxi Zhao ◽  
Xinyu Wang ◽  
...  
Keyword(s):  
Liver Injury ◽  
Signaling Pathway ◽  
Cholestatic Liver Disease ◽  
P53 Signaling ◽  
Promising Target ◽  
Underlying Mechanisms ◽  
Cholestatic Liver Injury ◽  
P53 Signaling Pathway

Background and purpose: FXR is a promising target for the treatment of human cholestatic liver disease (CLD). SIRT1 is a deacetylase which promotes FXR activity through deacetylating FXR. Pterostilbene (PTE) is an activator of SIRT1. However, the role of PTE in cholestasis has so far not been investigated. We examined whether PTE treatment alleviate liver injury in DDC or ANIT-induced experimental cholestasis, and explored the underlying mechanisms.Experimental approach: Mice with DDC- or ANIT-induced cholestasis were treated with different dose of PTE. Primary hepatocytes and bone marrow derived macrophages were used in vitro to assess the molecular mechanism by which PTE may improve CLD. Identical doses of UDCA or PTE were administered to DDC- or ANIT-induced cholestasis mice.Key results: PTE intervention attenuated DDC or ANIT-induced cholestasis. PTE inhibited macrophage infiltration and activation in mouse liver through the SIRT1-p53 signaling pathway, and it improved hepatic bile metabolism through the SIRT1-FXR signaling pathway. Compare with UDCA, the same doses of PTE was more effective in improving cholestatic liver injury caused by DDC or ANIT.Conclusion and implications: SIRT1 activation in macrophages may be an effective CLD treatment avenue. Using CLD models, we thus identified PTE as a novel clinical candidate compound for the treatment of CLD.

scholarly journals Neoagarooligosaccharide Protects against Hepatic Fibrosis via Inhibition of TGF-β/Smad Signaling Pathway

2021 ◽  
Vol 22 (4) ◽  
pp. 2041
Author(s):  
Ji Hye Yang ◽  
Sae Kwang Ku ◽  
IL Je Cho ◽  
Je Hyeon Lee ◽  
Chang-Su Na ◽  
...  
Keyword(s):  
Liver Injury ◽  
Signaling Pathway ◽  
Hepatic Fibrosis ◽  
Inflammatory Responses ◽  
Chronic Liver ◽  
Mrna Levels ◽  
Chronic Liver Injury ◽  
Smad Signaling ◽  
Smad Signaling Pathway

Hepatic fibrosis occurs when liver tissue becomes scarred from repetitive liver injury and inflammatory responses; it can progress to cirrhosis and eventually to hepatocellular carcinoma. Previously, we reported that neoagarooligosaccharides (NAOs), produced by the hydrolysis of agar by β-agarases, have hepatoprotective effects against acetaminophen overdose-induced acute liver injury. However, the effect of NAOs on chronic liver injury, including hepatic fibrosis, has not yet been elucidated. Therefore, we examined whether NAOs protect against fibrogenesis in vitro and in vivo. NAOs ameliorated PAI-1, α-SMA, CTGF and fibronectin protein expression and decreased mRNA levels of fibrogenic genes in TGF-β-treated LX-2 cells. Furthermore, downstream of TGF-β, the Smad signaling pathway was inhibited by NAOs in LX-2 cells. Treatment with NAOs diminished the severity of hepatic injury, as evidenced by reduction in serum alanine aminotransferase and aspartate aminotransferase levels, in carbon tetrachloride (CCl4)-induced liver fibrosis mouse models. Moreover, NAOs markedly blocked histopathological changes and collagen accumulation, as shown by H&E and Sirius red staining, respectively. Finally, NAOs antagonized the CCl4-induced upregulation of the protein and mRNA levels of fibrogenic genes in the liver. In conclusion, our findings suggest that NAOs may be a promising candidate for the prevention and treatment of chronic liver injury via inhibition of the TGF-β/Smad signaling pathway.

Vitexin protects against ethanol-induced liver injury through Sirt1/p53 signaling pathway

2020 ◽  
Vol 873 ◽  
pp. 173007 ◽  
Author(s):  
Huiqi Yuan ◽  
Shuni Duan ◽  
Ting Guan ◽  
Xin Yuan ◽  
Jizong Lin ◽  
...  
Keyword(s):  
Liver Injury ◽  
Signaling Pathway ◽  
P53 Signaling ◽  
P53 Signaling Pathway

The Molecular Docking of Flavonoids Isolated from Daucus carota as a Dual Inhibitor of MDM2 and MDMX

2020 ◽  
Vol 15 (2) ◽  
pp. 154-164 ◽  
Author(s):  
Ijaz Muhammad ◽  
Noor Rahman ◽  
Gul E. Nayab ◽  
Sadaf Niaz ◽  
Mohibullah Shah ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Cancer Therapy ◽  
Natural Product ◽  
Signaling Pathway ◽  
In Silico ◽  
P53 Protein ◽  
Dual Inhibitor ◽  
P53 Signaling ◽  
In Silico Studies ◽  
P53 Signaling Pathway

Background: Cancer is characterized by overexpression of p53 associated proteins, which down-regulate P53 signaling pathway. In cancer therapy, p53 activity can be restored by inhibiting the interaction of MDMX (2N0W) and MDM2 (4JGR) proteins with P53 protein. Objective: In the current, study in silico approaches were adapted to use a natural product as a source of cancer therapy. Methods: In the current study in silico approaches were adapted to use a natural product as a source of cancer therapy. For in silico studies, Chemdraw and Molecular Operating Environment were used for structure drawing and molecular docking, respectively. Flavonoids isolated from D. carota were docked with cancerous proteins. Result: Based on the docking score analysis, we found that compound 7 was the potent inhibitor of both cancerous proteins and can be used as a potent molecule for inhibition of 2N0W and 4JGR interaction with p53. Conclusion: Thus the compound 7 can be used for the revival of p53 signaling pathway function however, intensive in vitro and in vivo experiments are required to prove the in silico analysis.

Sign in / Sign up

Export Citation Format

Share Document