scholarly journals Hepatoprotective Effects of Antrodia cinnamomea: The Modulation of Oxidative Stress Signaling in a Mouse Model of Alcohol-Induced Acute Liver Injury

2017 ◽  
Vol 2017 ◽  
pp. 1-12 ◽  
Author(s):  
Yange Liu ◽  
Juan Wang ◽  
Lanzhou Li ◽  
Wenji Hu ◽  
Yidi Qu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Liver Injury ◽  
Mouse Model ◽  
Caspase 3 ◽  
Acute Liver Injury ◽  
Nuclear Factor ◽  
Related Factors ◽  
Inflammatory Infiltration ◽  
Hepatoprotective Effects ◽  
Underlying Mechanisms

In the present study, the components of A. cinnamomea (AC) mycelia were systematically analyzed. Subsequently, its hepatoprotective effects and the underlying mechanisms were explored using a mouse model of acute alcohol-induced liver injury. AC contained 25 types of fatty acid, 16 types of amino acid, 3 types of nucleotide, and 8 types of mineral. The hepatoprotective effects were observed after 2 weeks of AC treatment at doses of 75 mg/kg, 225 mg/kg, and 675 mg/kg in the mouse model. These effects were indicated by the changes in the levels of aspartate aminotransferase, alanine aminotransferase, several oxidation-related factors, and inflammatory cytokines in serum and/or liver samples. AC reduced the incidence rate of necrosis, inflammatory infiltration, fatty droplets formation, and cell apoptosis in liver detecting via histological and TUNEL assay. In addition, AC reduced the expression of cleaved caspase-3, -8, and -9 and the levels of phosphor-protein kinase B (Akt) and phosphor-nuclear factor-κB (NF-κB) in the liver samples. Collectively, AC-mediated hepatoprotective effects in a mouse model of acute alcohol-induced liver injury are the result of reduction in oxidative stress. This may be associated with Akt/NF-κB signaling. These results provide valuable evidence to support the use of A. cinnamomea as a functional food and/or medicine.

scholarly journals A Discovery of Relevant Hepatoprotective Effects and Underlying Mechanisms of Dietary Clostridium butyricum Against Corticosterone-Induced Liver Injury in Pekin Ducks

2019 ◽  
Vol 7 (9) ◽  
pp. 358 ◽  
Author(s):  
Yanhan Liu ◽  
Cun Liu ◽  
Liqing Huang ◽  
Zhaofei Xia
Keyword(s):  
Oxidative Stress ◽  
Lipid Metabolism ◽  
Liver Injury ◽  
Signaling Pathway ◽  
Basal Diet ◽  
Clostridium Butyricum ◽  
Pekin Ducks ◽  
Injury Model ◽  
Hepatoprotective Effects ◽  
Underlying Mechanisms

Clostridium butyricum (C. butyricum) can attenuate oxidative stress, inflammation, and hepatic fatty deposition in poultry, however, the underlying mechanisms for this in Pekin ducks remain unclear. This study evaluated these hepatoprotective effects and the underlying mechanisms in a corticosterone (CORT)-induced liver injury model in Pekin ducks fed a C. butyricum intervention diet. A total of 500 Pekin ducks were randomly divided into five groups: one group (CON group) was only provided with a basal diet, three groups were provided a basal diet with 200 mg/kg (LCB group), 400 mg/kg (MCB group), or 600 mg/kg (HCB group) C. butyricum, respectively, and one group was provided a basal diet with 150 mg/kg aureomycin (ANT group) for 42 d. At 37 days-old, all ducks received daily intraperitoneal injections of CORT for five days to establish a liver injury model. C. butyricum intervention alleviated liver injury by decreasing the liver organ indices, hepatic steatosis and hepatocyte necrosis, and improving liver function, antioxidant capacity, and inflammatory factors. Hepatic RNA-seq revealed 365 differentially expressed genes (DEGs) between the MCB and CON groups, with 229 up- and 136 down-regulated DEGs in the MCB group. Between the MCB and ANT groups, 407 DEGs were identified, including 299 up- and 108 down-regulated genes in MCB group. Some DEGs in the MCB group related to oxidative stress and inflammatory responses such as Sod3, Tlr2a/b, and Il10, which were up-regulated, while Apoa1, Cyp7a1, Acsl1/5, Fasn, Ppar-γ, and Scd, which are involved in lipid metabolism, were down-regulated, indicating that these genes were responsive to dietary C. butyricum for the alleviation of corticosterone-induced hepatic injury. Toll-like receptor signaling, PI3K-Akt signaling pathway, cytokine-cytokine receptor interaction, peroxisome proliferator-activated receptor (PPAR) signaling pathway, adipocytokine and glycerophospholipid metabolism signaling pathway were significantly enriched in the MCB group. These findings indicate that C. butyricum intervention can protect Pekin ducks from corticosterone-induced liver injury by the modulation of immunoregulatory- and lipid metabolism-related genes and pathways.

Epimedium koreanum Ameliorates Oxidative Stress-Mediated Liver Injury by Activating Nuclear Factor Erythroid 2-Related Factor 2

2018 ◽  
Vol 46 (02) ◽  
pp. 469-488 ◽  
Author(s):  
Ji Yun Jung ◽  
Sang Mi Park ◽  
Hae Li Ko ◽  
Jong Rok Lee ◽  
Chung A Park ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Liver Injury ◽  
Hepg2 Cells ◽  
Liver Diseases ◽  
Caspase 3 ◽  
Glutathione Depletion ◽  
Related Factor ◽  
Nuclear Factor ◽  
Nrf2 Activation ◽  
Anti Oxidant

Oxidative stress induced by reactive oxygen species is the main cause of various liver diseases. This study investigated the hepatoprotective effect of Epimedium koreanum Nakai water extract (EKE) against arachidonic acid (AA)[Formula: see text][Formula: see text][Formula: see text]iron-mediated cytotoxicity in HepG2 cells and carbon tetrachloride (CCl4-)-mediated acute liver injury in mice. Pretreatment with EKE (30 and 100[Formula: see text][Formula: see text]g/mL) significantly inhibited AA[Formula: see text][Formula: see text][Formula: see text]iron-mediated cytotoxicity in HepG2 cells by preventing changes in the expression of cleaved caspase-3 and poly(ADP-ribose) polymerase. EKE attenuated hydrogen peroxide production, glutathione depletion, and mitochondrial membrane dysfunction. EKE also increased the nuclear translocation of nuclear factor erythroid 2-related factor 2 (Nrf2), transactivated anti-oxidant response element harboring luciferase activity, and induced the expression of anti-oxidant genes. Furthermore, the cytoprotective effect of EKE against AA[Formula: see text][Formula: see text][Formula: see text]iron was blocked in Nrf2 knockout cells. Ultra-performance liquid chromatography analysis showed that EKE contained icariin, icaritin, and quercetin; icaritin and quercetin were both found to protect HepG2 cells from AA[Formula: see text][Formula: see text][Formula: see text]iron via Nrf2 activation. In a CCl4-induced mouse model of liver injury, pretreatment with EKE (300[Formula: see text]mg/kg) for four consecutive days ameliorated CCl4-mediated increases in serum aspartate aminotransferase activity, histological activity index, hepatic parenchyma degeneration, and inflammatory cell infiltration. EKE also decreased the number of nitrotyrosine-, 4-hydroxynonenal-, cleaved caspase-3-, and cleaved poly(ADP-ribose) polymerase-positive cells in hepatic tissues. These results suggest EKE is a promising candidate for the prevention or treatment of oxidative stress-related liver diseases via Nrf2 activation.

scholarly journals Hepatoprotective Effects of Different Extracts From Triphala Against CCl4-Induced Acute Liver Injury in Mice

2021 ◽  
Vol 12 ◽  
Author(s):  
Xichuan Wei ◽  
Chuanhong Luo ◽  
Yanan He ◽  
Haozhou Huang ◽  
Fei Ran ◽  
...  
Keyword(s):  
Liver Injury ◽  
Mouse Model ◽  
Protein Expression ◽  
Acute Liver Injury ◽  
Quinone Oxidoreductase ◽  
Tnf Α ◽  
Gene And Protein Expression ◽  
Wide Range ◽  
Hepatoprotective Effects ◽  
The Impact

Background:Triphala is a traditional polyherbal formula used in Indian Ayurvedic and Chinese Tibetan medicine. A wide range of biological activities have been attributed to Triphala, but the impact of various extraction methods on efficacy has not been determined.Purpose: The study aimed to evaluate Triphala extracts obtained by various methods for their hepatoprotective effects and molecular mechanisms in a mouse model of carbon tetrachloride (CCl4)-induced liver injury.Methods: HPLC fingerprinting was used to characterize the chemical characteristics of Triphala extracts obtained by (a) 0.5 h ultrasonication, (b) 2 h reflux, and (c) 4 h reflux. Hepatoprotective efficacy was evaluated in a mouse model of CCl4-induced liver damage. Serum levels of alanine transaminase (ALT) and aspartate aminotransferase (AST) were measured, as well as the liver antioxidant and inflammatory markers malondialdehyde superoxide dismutase glutathione peroxidase (GSH-Px), TNF-α, and IL-6. Gene and protein expression of Nrf-2 signaling components Nrf-2, heme oxygenase (HO-1), and NADPH Quinone oxidoreductase (NQO-1) in liver tissue were evaluated by real-time PCR and western blotting.Results: Chemical analysis showed a clear difference in content between extracts produced by ultrasonic and reflux methods. The pharmacological analysis showed that all three Triphala extracts reduced ALT, AST, MDA, TNF-α, and IL-6 levels and increased SOD and GSH-Px. Triphala extracts also induced transcript and protein expression of Nrf-2, HO-1, and NQO-1.Conclusion: Triphala extract prevents CCl4-induced acute liver injury. The ultrasonic extract of Triphala was most effective, suggesting that hepatoprotection may be related to the larger tannins via activation of Nrf-2 signaling.

scholarly journals Diallyl sulfide treatment protects against acetaminophen-/carbon tetrachloride-induced acute liver injury by inhibiting oxidative stress, inflammation and apoptosis in mice

2019 ◽  
Vol 8 (1) ◽  
pp. 67-76 ◽  
Author(s):  
Ming Li ◽  
Shuo Wang ◽  
Xianjie Li ◽  
Ruirui Kou ◽  
Qiong Wang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Carbon Tetrachloride ◽  
Liver Injury ◽  
Acute Liver Injury ◽  
Organosulfur Compound ◽  
Diallyl Sulfide ◽  
Drug Induced ◽  
Underlying Mechanisms

The purpose of the present study was to investigate the effects and underlying mechanisms of diallyl sulfide (DAS), an organosulfur compound extracted from garlic, on drug-induced or chemical-induced liver injury caused by acetaminophen (APAP) or carbon tetrachloride (CCl4) in mice.

scholarly journals Hepatoprotective Effects of Morchella esculenta against Alcohol-Induced Acute Liver Injury in the C57BL/6 Mouse Related to Nrf-2 and NF-κB Signaling

2019 ◽  
Vol 2019 ◽  
pp. 1-12
Author(s):  
Bo Meng ◽  
Yuanzhu Zhang ◽  
Zhuqian Wang ◽  
Qinran Ding ◽  
Jia Song ◽  
...  
Keyword(s):  
Superoxide Dismutase ◽  
Liver Injury ◽  
Heme Oxygenase ◽  
Liver Tissue ◽  
Nuclear Factor Kappa B ◽  
Acute Liver Injury ◽  
Nuclear Factor ◽  
Nuclear Factor Kappa ◽  
Morchella Esculenta ◽  
Hepatoprotective Effects

This study investigated the hepatoprotective effects of Morchella esculenta fruit body (ME) and the underlying mechanisms in mice with alcohol-induced acute liver injury. Systematic analysis revealed that ME contained 21 types of fatty acid, 17 types of amino acid, and 12 types of mineral. Subsequently, a mouse model of acute alcohol-induced liver injury was established by oral administration of alcohol for 14 days. Fourteen-day administration of ME prevented alcohol-induced increases in alanine aminotransferase and aspartate aminotransferase levels and reduced the activity of acetaldehyde dehydrogenase in blood serum and liver tissue. ME appears to regulate lipid metabolism by suppressing triglycerides, total cholesterol, and high-density lipoprotein in the liver. ME inhibited the production of inflammatory factors including chitinase-3-like protein 1 (YKL 40), interleukin-7 (IL-7), plasminogen activator inhibitor type 1 (PAI-1), and retinol-binding protein 4 (RBP4) in blood serum and/or liver tissue. ME treatment relieved the alcohol-induced imbalance in prooxidative and antioxidative signaling via nuclear factor-erythroid 2-related factor 2 (Nrf-2), as indicated by upregulation of superoxide dismutase-1, superoxide dismutase-2, catalase, heme oxygenase-1, and heme oxygenase-2 expression and downregulation of kelch-like ECH-associated protein 1 (Keap-1) in the liver. Moreover, ME reduced the levels of phosphorylated nuclear factor kappa-B kinase α/β, inhibitor of nuclear factor kappa-B α and nuclear factor kappa-B p65 (NF-κB p65) in the liver. The hepatoprotective effects of ME against alcohol-induced acute liver injury were thus confirmed. The mechanism of action may be related to modulation of antioxidative and anti-inflammatory signaling pathways, partially via regulation of Nrf-2 and NF-κB signaling.

Cytoprotective potential of tiron and methyl palmitate against acetaminophen-induced acute liver injury

2016 ◽  
Vol 94 (2) ◽  
pp. 147-154 ◽  
Author(s):  
Amal M. Shoeib ◽  
Eman Said ◽  
Elsayed M. Ammar
Keyword(s):  
Oxidative Stress ◽  
Liver Injury ◽  
Inflammatory Response ◽  
Biochemical Markers ◽  
Methyl Palmitate ◽  
Inflammatory Cytokine ◽  
Acute Liver Injury ◽  
Histopathological Examination ◽  
Hepatoprotective Effects ◽  
And Oxidative Stress

Acute liver injury is a debilitating disorder associated with loss of synthetic and detoxifying functions of the liver. This investigation was designed to assess cytoprotective efficacy of daily oral tiron (300 mg/kg) and daily oral methyl palmitate (300 mg/kg) against acetaminophen-induced acute liver injury. Rats were orally pretreated with either tiron or methyl palmitate at doses (300 mg/kg) for 7 days prior to oral acetaminophen (3 g/kg). Biochemical assay of markers of hepatotoxicity indices and oxidative stress was undertaken. Expression of inflammatory cytokine IL-6 was also evaluated. Histopathological examination of liver specimens was carried out as well. Both methyl palmitate and tiron significantly reversed the acetaminophen-induced elevation of biochemical markers (ALT, AST, and ALP) with restoration of SOD levels. Serum albumin levels and GSH liver contents increased, but in a nonsignificant manner. Moreover, methyl palmitate and tiron significantly decreased the level of serum LDH and serum IL-6 levels. Histopathology revealed that tiron markedly reduced the extent of acetaminophen-induced necrosis and methyl palmitate moderately decreased the necrosis in liver tissue. Methyl palmitate (300 mg/kg) and tiron (300 mg/kg) demonstrated promising hepatoprotective effects against acetaminophen-induced acute liver injury via modulation of inflammatory response and alleviation of the oxidative stress, allowing the preservation of hepatic functions.

Explore the mechanism of Swertia mussotii Franch. for hepatoprotective effects with iTRAQ-LC-MS/MS

2020 ◽  
Vol 23 ◽  
Author(s):  
Haixia Yun ◽  
Xinyu Wu ◽  
Yiwei Ding ◽  
Wendou Xiong ◽  
Xianglan Duan ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Carbon Tetrachloride ◽  
Liver Injury ◽  
Aspartate Aminotransferase ◽  
Alanine Aminotransferase ◽  
Total Bilirubin ◽  
Acute Liver Injury ◽  
Proteome Analysis ◽  
Ppi Networks ◽  
Hepatoprotective Effects

Background and Objective : A Tibetan traditional herb named Swertia mussotii Franch., also called “Zangyinchen” by the local people of Qinghai-Tibet area, has been used to protect the liver from injury for many years. However, the curative effect and molecular mechanism of the herb have not been demonstrated clearly. Materials and Methods: In our study, serum alanine aminotransferase, aspartate aminotransferase, total bilirubin levels were examined after S. mussotii Franch. treatment in the acute liver injury of the carbon tetrachloride-induced rat model. Then, Proteome Analysis was applied to explore the potential mechanism of SMT for hepatoprotective effects after iTRAQLC-MS/MS analysis (isobaric tag for relative and absolute quantification-liquid chromatograph-mass spectrometer with tandem mass spectrometry). Results: Serum results showed, alanine aminotransferase, aspartate aminotransferase, total bilirubin levels of rats with acute liver injury were all improved with SMT treatment. Moreover, Proteome Analysis suggested that, with S. Mussotii Franch. treatment, the levels of lipid catabolic process and lipid homeostasis were all enhanced. And the results of protein-protein interaction (PPI) analysis illustrated that these proteins assembled in PPI networks were found almost significantly enriched in response to lipid, negative regulation of lipase activity, response to lipopolysaccharide etc. Furthermore, the downregulated MRP14 and MRP8 proteins were found involved in the lipid metabolism, which may indicate the mechanism of SMT protection liver from ALI induced by carbon tetrachloride. Conclusion: SMT herb could play a role in hepatoprotection and alleviate the effect of acute liver injury by impacting the lipid metabolism associated biological process.

Exercise and Stevia Rebaudiana (R) Extracts Attenuate Diabetic Cardiomyopathy in Type 2 Diabetic Rats: Possible Underlying Mechanisms

2020 ◽  
Vol 20 (7) ◽  
pp. 1117-1132
Author(s):  
Abdelaziz M. Hussein ◽  
Elsayed A. Eid ◽  
Ismaeel Bin-Jaliah ◽  
Medhat Taha ◽  
Lashin S. Lashin
Keyword(s):  
Oxidative Stress ◽  
Blood Glucose ◽  
Diabetic Cardiomyopathy ◽  
Caspase 3 ◽  
Stevia Rebaudiana ◽  
Diabetic Rats ◽  
Control Group ◽  
Underlying Mechanisms ◽  
Type 2 Diabetic

Background and Aims: In the current work, we studied the effects of exercise and stevia rebaudiana (R) extracts on diabetic cardiomyopathy (DCM) in type 2 diabetic rats and their possible underlying mechanisms. Methods: : Thirty-two male Sprague Dawley rats were randomly allocated into 4 equal groups; a) normal control group, b) DM group, type 2 diabetic rats received 2 ml oral saline daily for 4 weeks, c) DM+ Exercise, type 2 diabetic rats were treated with exercise for 4 weeks and d) DM+ stevia R extracts: type 2 diabetic rats received methanolic stevia R extracts. By the end of the experiment, serum blood glucose, HOMA-IR, insulin and cardiac enzymes (LDH, CK-MB), cardiac histopathology, oxidative stress markers (MDA, GSH and CAT), myocardial fibrosis by Masson trichrome, the expression of p53, caspase-3, α-SMA and tyrosine hydroxylase (TH) by immunostaining in myocardial tissues were measured. Results: T2DM caused a significant increase in blood glucose, HOMA-IR index, serum CK-MB and LDH, myocardial damage and fibrosis, myocardial MDA, myocardial α-SMA, p53, caspase-3, Nrf2 and TH density with a significant decrease in serum insulin and myocardial GSH and CAT (p< 0.05). On the other hand, treatment with either exercise or stevia R extracts significantly improved all studied parameters (p< 0.05). Moreover, the effects of stevia R was more significant than exercise (p< 0.05). Conclusion: Both exercise and methanolic stevia R extracts showed cardioprotective effects against DCM and Stevia R offered more cardioprotective than exercise. This cardioprotective effect of these lines of treatment might be due to attenuation of oxidative stress, apoptosis, sympathetic nerve density and fibrosis and upregulation of the antioxidant transcription factor, Nrf2.

Protocatechuic Acid Protects Platelets from Apoptosis via Inhibiting Oxidative Stress-Mediated PI3K/Akt/GSK3β Signaling

2021 ◽  
Author(s):  
Fuli Ya ◽  
Kongyao Li ◽  
Hong Chen ◽  
Zezhong Tian ◽  
Die Fan ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Caspase 3 ◽  
Protocatechuic Acid ◽  
Human Platelets ◽  
Ros Generation ◽  
Inhibitory Effects ◽  
Platelet Apoptosis ◽  
Phosphatidylserine Exposure ◽  
Underlying Mechanisms

AbstractOxidative stress plays crucial roles in initiating platelet apoptosis that facilitates the progression of cardiovascular diseases (CVDs). Protocatechuic acid (PCA), a major metabolite of anthocyanin cyanidin-3-O-β-glucoside (Cy-3-g), exerts cardioprotective effects. However, underlying mechanisms responsible for such effects remain unclear. Here, we investigate the effect of PCA on platelet apoptosis and the underlying mechanisms in vitro. Isolated human platelets were treated with hydrogen peroxide (H2O2) to induce apoptosis with or without pretreatment with PCA. We found that PCA dose-dependently inhibited H2O2-induced platelet apoptosis by decreasing the dissipation of mitochondrial membrane potential, activation of caspase-9 and caspase-3, and decreasing phosphatidylserine exposure. Additionally, the distributions of Bax, Bcl-xL, and cytochrome c mediated by H2O2 in the mitochondria and the cytosol were also modulated by PCA treatment. Moreover, the inhibitory effects of PCA on platelet caspase-3 cleavage and phosphatidylserine exposure were mainly mediated by downregulating PI3K/Akt/GSK3β signaling. Furthermore, PCA dose-dependently decreased reactive oxygen species (ROS) generation and the intracellular Ca2+ concentration in platelets in response to H2O2. N-Acetyl cysteine (NAC), a ROS scavenger, markedly abolished H2O2-stimulated PI3K/Akt/GSK3β signaling, caspase-3 activation, and phosphatidylserine exposure. The combination of NAC and PCA did not show significant additive inhibitory effects on PI3K/Akt/GSK3β signaling and platelet apoptosis. Thus, our results suggest that PCA protects platelets from oxidative stress-induced apoptosis through downregulating ROS-mediated PI3K/Akt/GSK3β signaling, which may be responsible for cardioprotective roles of PCA in CVDs.

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