scholarly journals Protective effects of chebulic acid from Terminalia chebula Retz. against t-BHP-induced oxidative stress by modulations of Nrf2 and its related enzymes in HepG2 cells

2018 ◽  
Vol 28 (2) ◽  
pp. 555-562
Author(s):  
Hye-Lim Jung ◽  
Sung-Yong Yang ◽  
Min Cheol Pyo ◽  
Chung-Oui Hong ◽  
Mi-Hyun Nam ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Hepg2 Cells ◽  
Protective Effects ◽  
Terminalia Chebula ◽  
Chebulic Acid

The protective effects of carvacrol and thymol against paracetamol–induced toxicity on human hepatocellular carcinoma cell lines (HepG2)

2016 ◽  
Vol 35 (12) ◽  
pp. 1252-1263 ◽  
Author(s):  
SS Palabiyik ◽  
E Karakus ◽  
Z Halici ◽  
E Cadirci ◽  
Y Bayir ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Inflammatory Cytokines ◽  
Hepg2 Cells ◽  
Folk Medicine ◽  
Hepatoprotective Activity ◽  
High Dose ◽  
Protective Effects ◽  
And Oxidative Stress ◽  
Pro Inflammatory Cytokines

Acetaminophen (APAP) overdose could induce liver damage and lead to acute liver failure. The treatment of APAP overdoses could be improved by new therapeutic strategies. Thymus spp., which has many beneficial effects and has been used in folk medicine, is one such potential strategy. In the present study, the hepatoprotective activity of the main constituents of Thymus spp., carvacrol and thymol, were evaluated in light of APAP-induced hepatotoxicity. We hoped to understand the hepatoprotective mechanism of these agents on the antioxidant system and pro-inflammatory cytokines in vitro. Dose-dependent effects of thymol and carvacrol (25, 50, and 100 µM) were tested on cultured HepG2 cells. N-Acetylcysteine (NAC) was tested as positive control. We showed that APAP inhibited HepG2 cell growth by inducing inflammation and oxidative stress. Incubating APAP-exposed HepG2 cells with carvacrol and thymol for 24 h ameliorated this inflammation and oxidative stress. We also evaluated alanine transaminase and lactate dehydrogenase levels of HepG2 cells. We found that thymol and carvacrol protected against APAP-induced toxicity in HepG2 cells by increasing antioxidant activity and reducing pro-inflammatory cytokines, such as tumor necrosis factor α and interleukin 1β. Taking together high-dose thymol and carvacrol treatment has an effect close to NAC treatment in APAP toxicity, but thymol has better treatment effect than carvacrol.

scholarly journals Alkyl Hydroxytyrosyl Ethers Show Protective Effects against Oxidative Stress in HepG2 Cells

2011 ◽  
Vol 59 (11) ◽  
pp. 5964-5976 ◽  
Author(s):  
Gema Pereira-Caro ◽  
Beatriz Sarriá ◽  
Andrés Madrona ◽  
José Luis Espartero ◽  
Luis Goya ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Hepg2 Cells ◽  
Protective Effects

scholarly journals Dihydromyricetin Attenuates Palmitate Acid-Induced Oxidative Stress by promoting Autophagy via SIRT3-ATG4B Signaling in Hepatocytes

2021 ◽  
Author(s):  
Mantian Mi ◽  
Li Huang ◽  
Xianglong Zeng ◽  
Bo Li ◽  
Cong Wang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Hepg2 Cells ◽  
Underlying Mechanism ◽  
Protective Effects ◽  
Inhibitory Effects ◽  
Potential Therapeutic Target ◽  
Mitochondrial Ros ◽  
Intracellular Ros ◽  
Protein Expressions ◽  
And Oxidative Stress

Abstract Background Oxidative stress in hepatocytes was an important pathogenesis of nonalcoholic steatohepatitis (NASH). Autophagy was a cellular process that can remove damaged organelles under oxidative stress, and thus presented a potential therapeutic target against NASH. The aim of this work was to investigate whether autophagy participated the protective effects of dihydromyricetin (DHM) on palmitic acid (PA)-induced oxidative stress in hepatocytes and the underlying mechanism. Methods HepG2 cells were pretreated with DHM (20 µM) for 2 h, followed by PA (0.2 mM) treatment for 16 h. The oxidative stress was assessed by the quantification of intracellular reactive oxygen species (ROS), mitochondrial ROS (mtROS), mitochondrial membrane potential (MMP) and mitochondrial ultrastructural analyses. The protein expressions of SIRT3, LC3I/II, P62 and ATG4B, as well as the acetylation of AGT4B were determined by western blotting using HepG2 and HepG2/ ATG4B+/− cells with heterozygous knockout of ATG4B. Results Exposure to PA resulted in increased intracellular ROS and mtROS, decreased MMP and aggravated mitochondrial injury in HepG2 cells, which were notably attenuated by DHM treatment. DHM-induced inhibition of oxidative stress was associated with the induction of autophagy, characterized by upregulated ATG4B and LC3 II as well as downregulated P62 levels. Furthermore, the inhibitory effects of DHM on PA-induced autophagy arrest and oxidative stress were eliminated when pretreated with a SIRT3 inhibitor 3-TYP or conducted in HepG2/ATG4B+/− cells, suggesting that SIRT3 and ATG4B were involved in DHM-induced benefits. Moreover, DHM treatment increased the protein expression of SIRT3 and SIRT3-dependent deacetylation of ATG4B in HepG2 cells. Conclusion Our results demonstrated that DHM attenuated PA-induced oxidative stress in hepatocytes through induction of autophagy, which was mediated through the increased expression of SIRT3 and SIRT3-mediated ATG4B deacetylation following DHM treatment.

scholarly journals Gentiopicroside Ameliorates Oxidative Stress and Lipid Accumulation through Nuclear Factor Erythroid 2-Related Factor 2 Activation

2020 ◽  
Vol 2020 ◽  
pp. 1-13
Author(s):  
Meiyu Jin ◽  
Haihua Feng ◽  
Yue Wang ◽  
Siru Yan ◽  
Bingyu Shen ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Oxidative Damage ◽  
Lipid Accumulation ◽  
Hepg2 Cells ◽  
Regulatory Element ◽  
Cell Counting ◽  
Related Factor ◽  
Nuclear Factor ◽  
Protective Effects ◽  
Akt Inhibitor

The activation of nuclear factor erythroid 2-related factor 2 (Nrf2) is closely related to the alleviation of nonalcoholic fatty liver disease (NAFLD) by regulating oxidative stress and lipid homeostasis. Gentiopicroside (GPS), an iridoid glycoside found in the Gentianaceae, possesses anti-inflammatory and antioxidant effects. However, the protective effects of GPS on lipid accumulation and oxidative damage have not been investigated thoroughly in free fatty acid- (FFA-) induced HepG2 cells and tyloxapol- (Ty-) induced hyperlipidemia mice. Cell counting kit-8 assays, Oil Red O staining, Western blotting analysis, extraction of nuclear and cytosolic proteins, and biochemical index assay were employed to explore the mechanisms by which GPS exerts a protective effect on FFA-induced HepG2 cells and Ty-induced hyperlipidemia mouse model. This paper demonstrates that GPS could effectively alleviate NAFLD by elevating cell viability, reducing fatty deposition, downregulating TG, and activating nucleus Nrf2 in FFA-induced HepG2 cells. Meanwhile, GPS significantly regulated the activation of phosphatidylinositol 3-kinase (PI3K)/AKT signaling pathway, Nrf2 antioxidant pathway, peroxisome proliferator-activated receptor α (PPARα), and GPS-inhibited sterol regulatory element-binding protein-1c (SREBP-1c) expression in FFA-stimulated lipid accumulation of HepG2 cells and Ty-treated mice. Interestingly, we highlight that PI3K/AKT inhibitor (LY294002) markedly increased the expression of Nrf2 antioxidant pathway, PPARα, and downregulated SREBP-1c in FFA-stimulated HepG2 cells. For these reasons, we found that the deletion of Nrf2 could lose the protective effects of GPS on the Nrf2 antioxidant pathway and PPARα activation and SREBP-1c inactivation in FFA-stimulated HepG2 cells and Ty-treated mice. GPS treatment had no effect on abnormal lipogenesis and antioxidant enzymes in Ty-induced Nrf2-/- mice. This work gives a new explanation that GPS may be a useful therapeutic strategy for NAFLD through upregulation of the Nrf2 antioxidant pathway, which can alleviate oxidative damage and lipid accumulation.

scholarly journals Physicochemical Properties and Effects of Honeys on Key Biomarkers of Oxidative Stress and Cholesterol Homeostasis in HepG2 Cells

Nutrients ◽  
2021 ◽  
Vol 13 (1) ◽  
pp. 151
Author(s):  
Huong Thi Lan Nguyen ◽  
Stefan Kasapis ◽  
Nitin Mantri
Keyword(s):  
Oxidative Stress ◽  
Hepg2 Cells ◽  
Antioxidant Activities ◽  
Biochemical Properties ◽  
Cholesterol Homeostasis ◽  
Protective Effects ◽  
Cholesterol Reduction ◽  
Phenolic Contents ◽  
Biomarkers Of Oxidative Stress ◽  
Newtonian Behavior

Manuka honey and newly developed honeys (arjuna, guggul, jiaogulan and olive) were examined for their physicochemical, biochemical properties and effects on oxidative stress and cholesterol homeostasis in fatty acid-induced HepG2 cells. The honeys exhibited standard moisture content (<20%), electrical conductivity (<0.8 mS/cm), acidic pH, and monosaccharides (>60%), except olive honey (<60% total monosaccharides). They all expressed non-Newtonian behavior and 05 typical regions of the FTIR spectra as those of natural ones. Guggul and arjuna, manuka honeys showed the highest phenolic contents, correlating with their significant antioxidant activities. Arjuna, guggul and manuka honeys demonstrated the agreement of total cholesterol reduction and the transcriptional levels of AMPK, SREBP2, HCMGR, LDLR, LXRα. Jiaogulan honey showed the least antioxidant content and activity, but it was the most cytotoxic. Both jiaogulan and olive honeys modulated the tested gene in the pattern that should lead to a lower TC content, but this reduction did not occur after 24 h. All 2% concentrations of tested honeys elicited a clearer effect on NQO1 gene expression. In conclusion, the new honeys complied with international norms for natural honeys and we provide partial evidence for the protective effects of manuka, arjuna and guggul honeys amongst the tested ones on key biomarkers of oxidative stress and cholesterol homeostasis, pending further studies to better understand their modes of action.

scholarly journals Activation of the Keap1-Nrf2 pathway by specioside and the n-butanol extract from the inner bark of Tabebuia rosea (Bertol) DC

F1000Research ◽  
2020 ◽  
Vol 9 ◽  
pp. 1262
Author(s):  
Sandra Catalina Garzón-Castaño ◽  
Francisco Javier Jiménez-González ◽  
Luz Angela Veloza ◽  
Juan Carlos Sepúlveda-Arias
Keyword(s):  
Oxidative Stress ◽  
Transcription Factor ◽  
Hepg2 Cells ◽  
Radical Scavenging ◽  
Protective Effects ◽  
Nrf2 Pathway ◽  
Butanol Extract ◽  
Inner Bark ◽  
Mtt Method ◽  
Tabebuia Rosea

Background: A large number of chemical compounds exert their antioxidant effects by activation of key transcriptional regulatory mechanisms, such as the transcription factor Nrf2. The aim of this study was to evaluate the activation of the Keap1-Nrf2 pathway by both the n-butanol extract obtained from the inner bark of Tabebuia rosea (Bertol) DC and specioside isolated from this extract. Methods: The antioxidant activity of the extract and specioside isolated from the inner bark of T. rosea were evaluated using the oxygen radical absorbance capacity (ORAC) and the 2,2-diphenyl-1-picrylhydrazyl radical scavenging activity (DPPH) techniques, whereas their effects on the viability of HepG2 cells was determined using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method. The effects of the compound and the extract on activating the Keap1-Nrf2 pathway were evaluated using a Nrf2 Transcription Factor Assay kit. Induction of the Nrf2-mediated antioxidant response genes HMOX-1 and NQO1 was evaluated by real-time PCR. The protective effects against H2O2-induced oxidative stress in HepG2 cells was determined as the percent protection using the MTT method. Results: Both the n-butanol extract and specioside exhibited activity at low concentrations without affecting cellular viability, since the cell viability was greater than 80% after 24 hours of exposure at each tested concentration. In addition, Nrf2 dissociated from Keap1 after treatment with the n-butanol extract at a concentration of 0.25 µg/mL after 4 hours of exposure. An increase in the Nrf2 level in the cytoplasm after 4 hours of exposure to 2 μM specioside was observed. Nrf2 levels stabilized in the nucleus 12 hours after stimulation with both specioside and the extract. After 6 hours of stimulation, both the extract and specioside induced the expression of HMOX-1 and NQO1. Conclusion: The n-butanol extract from the inner bark of T. rosea and specioside produced protective effects against H2O2-induced oxidative stress in HepG2 cells.

scholarly journals SIRT3-dependent mitochondrial oxidative stress in sodium fluoride-induced hepatotoxicity and salvage by melatonin

2017 ◽  
Author(s):  
Chao Song ◽  
Jiamin Zhao ◽  
Jingcheng Zhang ◽  
Tingchao Mao ◽  
Beibei Fu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Hepg2 Cells ◽  
Binding Activity ◽  
Daily Injection ◽  
Mechanistic Study ◽  
Peroxisome Proliferator ◽  
Protective Effects ◽  
Peroxisome Proliferator Activated Receptor

AbstractOxidative stress induced by fluoride (F) is associated with fluorosis formation, but the underlying molecular mechanism remains unclear. In this study, Melatonin pretreatment suppressed F-induced hepatocyte injury in HepG2 cells. Melatonin increases the activity of superoxide dismutase (SOD2) by enhancing sirtuin 3 (SIRT3)-mediated deacetylation and promotes SOD2 gene expression via SIRT3-regulated DNA-binding activity of forkhead box O3 (FoxO3a), indicating that melatonin markedly enhanced mROS scavenging in F-exposed HepG2 cells. Notably, melatonin activated the peroxisome proliferator-activated receptor gamma coactivator 1α (PGC-1α). PGC-1α interacted with the estrogen-related receptor alpha (ERRα) bound to the SIRT3 promoter, where it functions as a transcription factor to regulate SIRT3 expression. Furthermore, daily injection of melatonin for 30 days inhibited F-induced oxidative stress in mice liver, leading to improvement of liver function. Mechanistic study revealed that the protective effects of melatonin were associated with down-regulation of JNK1/2 phosphorylation in vitro and in vivo. Collectively, our data suggest a novel role of melatonin in preventing F-induced oxidative stress through activation of the SIRT3 pathway.

scholarly journals Activation of the Keap1-Nrf2 pathway by specioside and the n-butanol extract from the inner bark of Tabebuia rosea (Bertol) DC

F1000Research ◽  
2020 ◽  
Vol 9 ◽  
pp. 1262
Author(s):  
Sandra Catalina Garzón-Castaño ◽  
Francisco Javier Jiménez-González ◽  
Luz Angela Veloza ◽  
Juan Carlos Sepúlveda-Arias
Keyword(s):  
Oxidative Stress ◽  
Transcription Factor ◽  
Hepg2 Cells ◽  
Radical Scavenging ◽  
Protective Effects ◽  
Nrf2 Pathway ◽  
Butanol Extract ◽  
Inner Bark ◽  
Mtt Method ◽  
Tabebuia Rosea

Background: A large number of chemical compounds exert their antioxidant effects by activation of key transcriptional regulatory mechanisms, such as the transcription factor Nrf2. The aim of this study was to evaluate the activation of the Keap1-Nrf2 pathway by both the n-butanol extract obtained from the inner bark of Tabebuia rosea (Bertol) DC and specioside isolated from this extract. Methods: The antioxidant activity of the extract and specioside isolated from the inner bark of T. rosea were evaluated using the oxygen radical absorbance capacity (ORAC) and the 2,2-diphenyl-1-picrylhydrazyl radical scavenging activity (DPPH) techniques, whereas their effects on the viability of HepG2 cells was determined using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method. The effects of the compound and the extract on activating the Keap1-Nrf2 pathway were evaluated using a Nrf2 Transcription Factor Assay kit. Induction of the Nrf2-mediated antioxidant response genes HMOX-1 and NQO1 was evaluated by real-time PCR. The protective effects against H2O2-induced oxidative stress in HepG2 cells was determined as the percent protection using the MTT method. Results: Both the n-butanol extract and specioside exhibited activity at low concentrations without affecting cellular viability, since the cell viability was greater than 80% after 24 hours of exposure at each tested concentration. In addition, Nrf2 dissociated from Keap1 after treatment with the n-butanol extract at a concentration of 0.25 µg/mL after 4 hours of exposure. An increase in the Nrf2 level in the cytoplasm after 4 hours of exposure to 2 μM specioside was observed. Nrf2 levels stabilized in the nucleus 12 hours after stimulation with both specioside and the extract. After 6 hours of stimulation, both the extract and specioside induced the expression of HMOX-1 and NQO1. Conclusion: The n-butanol extract from the inner bark of T. rosea and specioside produced protective effects against H2O2-induced oxidative stress in HepG2 cells.

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