scholarly journals Fucoidan from Fucus vesiculosus Protects against Alcohol-Induced Liver Damage by Modulating Inflammatory Mediators in Mice and HepG2 Cells

Marine Drugs ◽  
2015 ◽  
Vol 13 (2) ◽  
pp. 1051-1067 ◽  
Author(s):  
Jung Lim ◽  
Sung Lee ◽  
Taeseong Kim ◽  
Seon-A Jang ◽  
Se Kang ◽  
...  
Keyword(s):  
Liver Damage ◽  
Inflammatory Mediators ◽  
Hepg2 Cells ◽  
Fucus Vesiculosus

scholarly journals Bamboo Stems (Phyllostachys nigra variety henosis) Containing Polyphenol Mixtures Activate Nrf2 and Attenuate Phenylhydrazine-Induced Oxidative Stress and Liver Injury

Nutrients ◽  
2019 ◽  
Vol 11 (1) ◽  
pp. 114 ◽  
Author(s):  
Ji Hye Yang ◽  
Moon-Hee Choi ◽  
Chang-Su Na ◽  
Sam Seok Cho ◽  
Jae Hoon Kim ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Liver Injury ◽  
Iron Overload ◽  
Liver Damage ◽  
Hepg2 Cells ◽  
Hepatoprotective Effect ◽  
Glutathione Depletion ◽  
Related Factor ◽  
Nrf2 Target Gene ◽  
Phyllostachys Nigra

This study was designed to investigate the hepatoprotective effect of bamboo stems using in vitro and in vivo experimental liver damage models. Ethyl acetate fraction of 80% ethanol extract of Phyllostachys nigra stem (PN3) containing polyphenols had a higher NQO1-ARE reporter gene activity as monitored by the activity of the NF-E2-related factor (Nrf2) antioxidant pathway in cells in comparison to extracts from other species and under other conditions. The Nrf2 was translocated from the cytosol to the nucleus in response to PN3, followed by induction of the Nrf2 target gene expression, including HO-1, GCL, and NQO-1 in HepG2 cells. Phosphorylation of Nrf2 in HepG2 cells was enhanced in PN3, which was mediated by PKCδ, ERK, and p38 MAPK. Consequently, PN3 inhibited arachidonic acid (AA) + iron-induced reactive oxygen species generation and glutathione depletion, and, thus, highlighted their role in cytotoxicity. Treatment with major polyphenols of PN3, including catechin, chlorogenic acid, caffeic acid, and p-coumaric acid, also improved AA + iron-mediated oxidative stress and, thus, improved cell viability. Treatment with phenylhydrazine in mice, i.e., the iron overload liver injury model, increased plasma alanine aminotransferase and aspartate aminotransferase levels and changed histological features in mice—a response that was almost completely blocked by PN3 administration. Moreover, PN3 extract mitigated phenylhydrazine-induced oxidative stress and inflammatory responses. Conclusively, PN3 can exert a hepatoprotective effect against iron overload-induced acute liver damage due to its antioxidant properties.

Pro-inflammatory cytokines reduce human TAFI expression via tristetraprolin-mediated mRNA destabilisation and decreased binding of HuR

2015 ◽  
Vol 114 (08) ◽  
pp. 337-349 ◽  
Author(s):  
Dragana Komnenov ◽  
Corey Scipione ◽  
Zainab Bazzi ◽  
Justin Garabon ◽  
Marlys Koschinsky ◽  
...  
Keyword(s):  
Inflammatory Cytokines ◽  
Inflammatory Mediators ◽  
Hepg2 Cells ◽  
Inflammatory Cells ◽  
Gene Encoding ◽  
Protein Levels ◽  
Anti Inflammatory ◽  
Mechanistic Basis ◽  
Pro Inflammatory Cytokines

SummaryThrombin activatable fibrinolysis inhibitor (TAFI) is the zymogen form of a basic carboxypeptidase (TAFIa) with both anti-fibrinolytic and anti-inflammatory properties. The role of TAFI in inflammatory disease is multifaceted and involves modulation both of specific inflammatory mediators as well as of the behaviour of inflammatory cells. Moreover, as suggested by in vitro studies, inflammatory mediators are capable of regulating the expression of CPB2, the gene encoding TAFI. In this study we addressed the hypothesis that decreased TAFI levels observed in inflammation are due to post-transcriptional mechanisms. Treatment of human HepG2 cells with pro-inflammatory cytokines TNFα, IL-6 in combination with IL-1β, or with bacterial lipopolysaccharide (LPS) decreased TAFI protein levels by approximately two-fold over 24 to 48 hours of treatment. Conversely, treatment of HepG2 cells with the anti-inflammatory cytokine IL-10 increased TAFI protein levels by two-fold at both time points. We found that the mechanistic basis for this modulation of TAFI levels involves binding of tristetraprolin (TTP) to the CPB2 3′-UTR, which mediates CPB2 mRNA destabilisation. In this report we also identified that HuR, another ARE-binding protein but one that stabilises transcripts, is capable of binding the CBP2 3’UTR. We found that pro-inflammatory mediators reduce the occupancy of HuR on the CPB2 3’-UTR and that the mutation of the TTP binding site in this context abolishes this effect, although TTP and HuR appear to contact discrete binding sites. Interestingly, all of the mediators tested appear to increase TAFI protein expression in THP-1 macrophages, likewise through effects on CPB2 mRNA stability.

scholarly journals Hepatoprotective Activity of BV-7310, a Proprietary Herbal Formulation of Phyllanthus niruri, Tephrosia purpurea, Boerhavia diffusa, and Andrographis paniculata, in Alcohol-Induced HepG2 Cells and Alcohol plus a Haloalkane, CCl4, Induced Liver Damage in Rats

2020 ◽  
Vol 2020 ◽  
pp. 1-9
Author(s):  
Debendranath Dey ◽  
Sunetra Chaskar ◽  
Narendra Bhatt ◽  
Deepa Chitre
Keyword(s):  
Body Weight ◽  
Liver Damage ◽  
Hepg2 Cells ◽  
Liver Toxicity ◽  
Hepatoprotective Activity ◽  
Andrographis Paniculata ◽  
Phyllanthus Niruri ◽  
In Vivo Models ◽  
Tephrosia Purpurea ◽  
Boerhavia Diffusa

Excessive alcohol consumption is a worldwide threat with severe morbidity and mortality. Other than abstinence, there is still no FDA-approved drug for alcoholic liver disease (ALD). Liver is the primary site of ethanol metabolism and hence gets the most damage from excessive drinking. It triggers multiple signalling events including inflammation, leading to an array of hepatic lesions like steatosis, hepatitis, fibrosis, and cirrhosis. Similarly, when medications or xenobiotic compounds are ingested orally, the liver gets the highest exposure of those metabolites, which in turn can cause severe liver toxicity. BV-7310 is a standardized mixture of four Ayurvedic plants, namely, Phyllanthus niruri, Tephrosia purpurea, Boerhavia diffusa, and Andrographis paniculata. In different systems of traditional medicine, each of these plants has been known to have use in gastrointestinal disorders. We wanted to assess the combined effect of these plant extracts on alcohol-induced liver damage. First, we investigated the hepatoprotective activity of BV-7310 against alcohol-induced toxicity in human liver HepG2 cells. Ethanol treatment (120 mM for 48 hours) significantly showed toxicity (around 42%) in these cells, and coincubation with BV-7310 prevented ethanol-induced cell death in a dose-dependent manner. Interestingly, the formulation BV-7310 showed synergistic activity than any individual extract tested in this assay. BV-7310 also showed potent antioxidant activity in 2,2-diphenyl-1-picryl-hydrazyl (DPPH) assay. Next, we induced hepatitis in Sprague–Dawley (SD) rats using repeated alcohol (40%) dosing, and carbon tetrachloride (CCl4) 24 hours before termination. Both oral doses of BV-7310 (250 and 500 mg/kg body weight) protected the alcohol-induced body weight loss and significantly improved the elevated levels of liver enzymes compared to the vehicle treated group. Thus, BV-7310 prevents alcohol-induced toxicity in both in-vitro and in-vivo models and could be beneficial for the treatment of ALD or other conditions, which may cause liver toxicity.

scholarly journals Effect of Capsosiphon fulvescens on Ethanol-induced Liver Damage in HepG2 Cells over Expressing CYP2E1

2017 ◽  
Vol 5 (7) ◽  
pp. 510-517 ◽  
Author(s):  
Haneul Jo ◽  
Ok-Kyung Kim ◽  
Ho-Geun Yoon ◽  
Eungpil Kim ◽  
Kyungmi Kim ◽  
...  
Keyword(s):  
Liver Damage ◽  
Hepg2 Cells ◽  
Capsosiphon Fulvescens

Untargeted metabolomic study of HepG2 cells under the effect of Fucus vesiculosus aqueous extract

2021 ◽  
Vol 35 (23) ◽  
Author(s):  
Rebeca André ◽  
Rita Guedes ◽  
Javier López ◽  
Maria Luísa Serralheiro
Keyword(s):  
Aqueous Extract ◽  
Hepg2 Cells ◽  
Fucus Vesiculosus ◽  
Metabolomic Study

Abstract 582: Inflammatory Cytokines Reduce Thrombin Activatable Fibrinolysis Inhibitor Protein Levels in HepG2 Cells via TTP-Mediated Destabilization of TAFI mRNA

2014 ◽  
Vol 34 (suppl_1) ◽  
Author(s):  
Dragana Novakovic ◽  
Michael B Boffa
Keyword(s):  
Inflammatory Cytokines ◽  
Inflammatory Mediators ◽  
Mrna Stability ◽  
Hepg2 Cells ◽  
Fusion Transcript ◽  
Thrombin Activatable Fibrinolysis Inhibitor ◽  
Protein Levels ◽  
Fibrinolysis Inhibitor ◽  
Anti Inflammatory

Thrombin activatable fibrinolysis inhibitor (TAFI) is the zymogen form of a basic carboxypeptidase (TAFIa) with both anti-fibrinolytic and anti-inflammatory properties. The role of TAFI in inflammatory disease is multifaceted and involves both recognition of specific pro-inflammatory substrates by TAFIa as well as regulation of TAFI gene expression by inflammatory mediators. In this study we addressed the hypothesis that decreased TAFI levels observed in inflammation are due to destabilization of its mRNA via the A/U-rich responsive element binding protein tristetraprolin (TTP). TAFI protein levels were measured in conditioned medium of HepG2 cells with recently developed assay specific for TAFIa. Treatment of cells with pro-inflammatory cytokines TNFα, IL-6 in combination with IL-1β, or with bacterial lipopolysaccharide (LPS) decreased TAFI protein levels by approximately 2-fold over 24 to 48 hours of treatment. Conversely, treatment of HepG2 cells with the anti-inflammatory cytokine IL-10 increased TAFI protein levels by 2-fold at both 24 and 48 hour time points. We employed luciferase reporter gene studies using human TAFI promoter constructs and found no change in promoter activity with these treatments. We then hypothesized that changes in mRNA stability may be involved through binding of TTP to the TAFI 3’-UTR, as we recently characterized the role of TTP in mediating TAFI mRNA stability. Using constructs expressing β-globin fusion mRNAs containing the TAFI 3’-UTR, we found that TNFα, IL-6, IL-1β, and LPS reduce TAFI mRNA half-life by 30%. This effect appears to be dependent on TTP binding, since these cytokines did not alter the stability of a fusion transcript lacking the TTP binding site. IL-10 caused an increase in fusion transcript stability by 38%, an effect that was also observed when the TTP binding site was mutated. Using reporter constructs expressing fusion mRNA’s containing the luciferase coding region and the TAFI 3’-UTR, we found that translation rate remained unaffected with both pro- and anti-inflammatory treatments. In conclusion, destabilization of TAFI mRNA appears to be the main mechanism behind decreased TAFI protein levels observed in the presence of pro-inflammatory mediators.

scholarly journals Dipeptide YA is Responsible for the Positive Effect of Oyster Hydrolysates on Alcohol Metabolism in Single Ethanol Binge Rodent Models

Marine Drugs ◽  
2020 ◽  
Vol 18 (10) ◽  
pp. 512
Author(s):  
Adrian S. Siregar ◽  
Marie Merci Nyiramana ◽  
Eun-Jin Kim ◽  
Eui-Jung Shin ◽  
Min Seok Woo ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Liver Damage ◽  
Inflammatory Mediators ◽  
Liver Toxicity ◽  
High Dose ◽  
Alcohol Metabolism ◽  
Single High Dose ◽  
Anti Inflammatory

Accumulative alcohol hangovers cause liver damage through oxidative and inflammatory stress. Numerous antioxidant and anti-inflammatory reagents have been developed to reduce alcohol hangovers, but these reagents are still insignificant and have limitations in that they can cause liver toxicity. Oyster hydrolysate (OH), another reagent that has antioxidant and anti-inflammatory activity, is a product extracted through an enzymatic hydrolysis process from oysters (Crassostrea gigas), which can be easily eaten in meals. This study was aimed at determining the effects of OH on alcohol metabolism, using a single high dose of ethanol (EtOH) administered to rodents, by monitoring alcohol metabolic enzymes, oxidative stress signals, and inflammatory mediators. The effect of tyrosine-alanine (YA) peptide, a main component of OH, on EtOH metabolism was also identified. In vitro experiments showed that OH pretreatment inhibited EtOH-induced cell death, oxidative stress, and inflammation in liver cells and macrophages. In vivo experiments showed that OH and YA pre-administration increased alcohol dehydrogenase, aldehyde dehydrogenase, and catalase activity in EtOH binge treatment. In addition, OH pre-administration alleviated CYP2E1 activity, ROS production, apoptotic signals, and inflammatory mediators in liver tissues. These results showed that OH and YA enhanced EtOH metabolism and had a protective effect against acute alcohol liver damage. Our findings offer new insights into a single high dose of EtOH drinking and suggest that OH and YA could be used as potential marine functional foods to prevent acute alcohol-induced liver damage.

Sign in / Sign up

Export Citation Format

Share Document