scholarly journals Galangin Activates Nrf2 Signaling and Attenuates Oxidative Damage, Inflammation, and Apoptosis in a Rat Model of Cyclophosphamide-Induced Hepatotoxicity

Biomolecules ◽  
2019 ◽  
Vol 9 (8) ◽  
pp. 346 ◽  
Author(s):  
Aladaileh ◽  
Abukhalil ◽  
Saghir ◽  
Hanieh ◽  
Alfwuaires ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Dna Damage ◽  
Liver Injury ◽  
Oxidative Damage ◽  
Biological Activities ◽  
B Cell Lymphoma ◽  
Heme Oxygenase 1 ◽  
Related Factor ◽  
Nuclear Factor ◽  
Quinone Acceptor

Cyclophosphamide (CP) is a widely used chemotherapeutic agent; however, its clinical application is limited because of its multi-organ toxicity. Galangin (Gal) is a bioactive flavonoid with promising biological activities. This study investigated the hepatoprotective effect of Gal in CP-induced rats. Rats received Gal (15, 30 and 60 mg/kg/day) for 15 days followed by a single dose of CP at day 16. Cyclophosphamide triggered liver injury characterized by elevated serum transaminases, alkaline phosphatase (ALP) and lactate dehydrogenase (LDH), and histopathological manifestations. Increased hepatic reactive oxygen species, malondialdehyde, nitric oxide, and oxidative DNA damage along with declined glutathione and antioxidant enzymes were demonstrated in CP-administered rats. CP provoked hepatic nuclear factor-kappaB (NF-κB) phosphorylation and increased mRNA abundance of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), and tumor necrosis factor-alpha (TNF-α) and interleukin-1 beta (IL-1β) both expression and serum levels. Gal prevented CP-induced liver injury, boosted antioxidants and suppressed oxidative stress, DNA damage, NF-κB phosphorylation and pro-inflammatory mediators. Gal diminished Bax and caspase-3, and increased B-cell lymphoma-2 (Bcl-2) in liver of CP-administered rats. In addition, Gal increased peroxisome proliferator-activated receptor gamma (PPARγ) expression and activated hepatic nuclear factor erythroid 2-related factor 2 (Nrf2) signaling showed by the increase in Nrf2, NAD(P)H: quinone acceptor oxidoreductase-1 (NQO-1) and heme oxygenase 1 (HO-1) in CP-administered rats. These findings suggest that Gal prevents CP hepatotoxicity through activation of Nrf2/HO-1 signaling and attenuation of oxidative damage, inflammation and cell death. Therefore, Gal might represent a promising adjuvant therapy to prevent hepatotoxicity in patients on CP treatment.

scholarly journals Antagonistic Efficacy of Luteolin against Lead Acetate Exposure-Associated with Hepatotoxicity is Mediated via Antioxidant, Anti-Inflammatory, and Anti-Apoptotic Activities

Antioxidants ◽  
2019 ◽  
Vol 9 (1) ◽  
pp. 10 ◽  
Author(s):  
Wafa A. AL-Megrin ◽  
Afrah F. Alkhuriji ◽  
Al Omar S. Yousef ◽  
Dina M. Metwally ◽  
Ola A. Habotta ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Lead Acetate ◽  
Interleukin 1 ◽  
Treated Group ◽  
Control Group ◽  
Heme Oxygenase 1 ◽  
Related Factor ◽  
Nuclear Factor ◽  
Toxic Heavy Metal ◽  
Anti Inflammatory

The abundant use of lead (Pb; toxic heavy metal) worldwide has increased occupational and ecosystem exposure, with subsequent negative health effects. The flavonoid luteolin (LUT) found in many natural foodstuffs possesses antioxidant and anti-inflammatory properties. Herein, we hypothesized that LUT could mitigate liver damage induced by exposure to lead acetate (PbAc). Male Wistar rats were allocated to four groups: control group received normal saline, LUT-treated group (50 mg/kg, oral, daily), PbAc-treated group (20 mg/kg, i.p., daily), and LUT+PbAc-treated group (received the aforementioned doses via the respective routes of administration); the rats were treated for 7 days. The results revealed that PbAc exposure significantly increased hepatic Pb residue and serum activities of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and total bilirubin value. Oxidative reactions were observed in the liver tissue following PbAc intoxication, characterized by the depletion and downregulation of antioxidant proteins (glutathione, glutathione reductase, glutathione peroxidase, superoxide dismutase, catalase, nuclear factor erythroid 2-related factor 2, and heme oxygenase-1), and an increase in oxidants (malondialdehyde and nitric oxide). Additionally, PbAc increased the release and expression of the pro-inflammatory cytokines (tumor necrosis factor alpha and interleukin-1 beta), inducible nitric oxide synthase, and nuclear factor kappa B. Moreover, PbAc enhanced hepatocyte loss by increasing the expression of pro-apoptotic proteins (Bax and caspase-3) and downregulating the anti-apoptotic protein (Bcl-2). The changes in the aforementioned parameters were further confirmed by noticeable histopathological lesions. LUT supplementation significantly reversed all of the tested parameters in comparison with the PbAc-exposed group. In conclusion, our findings describe the potential mechanisms involved in the alleviation of PbAc-induced liver injury by luteolin via its potent anti-inflammatory, antioxidant, and anti-apoptotic properties.

scholarly journals Synthetic Ruthenium Complex TQ-6 Potently Recovers Cerebral Ischemic Stroke: Attenuation of Microglia and Platelet Activation

2020 ◽  
Vol 9 (4) ◽  
pp. 996
Author(s):  
Chih-Hsuan Hsia ◽  
Thanasekaran Jayakumar ◽  
Joen-Rong Sheu ◽  
Chih-Wei Hsia ◽  
Wei-Chieh Huang ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Ischemic Stroke ◽  
Platelet Activation ◽  
Nuclear Translocation ◽  
Radical Scavenging ◽  
Microglia Activation ◽  
Heme Oxygenase 1 ◽  
Related Factor ◽  
Nuclear Factor ◽  
Cox 2

Activated microglia are crucial in the regulation of neuronal homeostasis and neuroinflammation. They also contribute to neuropathological processes after ischemic stroke. Thus, finding new approaches for reducing neuroinflammation has gained considerable attention. The metal ruthenium has gained notable attention because of its ability to form new complexes that can be used in disease treatment. [Ru(η6-cymene)2-(1H-benzoimidazol-2-yl)-quinoline Cl]BF4 (TQ-6), a potent ruthenium (II)-derived compound, was used in this study to investigate its neuroprotective action against microglia activation, middle cerebral artery occlusion (MCAO)-induced embolic stroke, and platelet activation, respectively. TQ-6 (2 μM) potently diminished inflammatory mediators (nitric oxide/inducible nitric oxide synthase (iNOS) and cyclooxygenase 2 (COX-2)) expression, nuclear factor kappa B (NF-κB) p65 phosphorylation, nuclear translocation, and hydroxyl radical (OH•) formation in LPS-stimulated microglia. Conversely, TQ-6 increased the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1). Moreover, it significantly reduced brain infarct volume and edema in MCAO mice. Additionally, it drastically inhibited platelet aggregation and OH• production in mice platelets. This study confirmed that TQ-6 exerts an anti-neuroinflammatory effect on microglia activation through neuroprotection, antiplatelet activation, and free radical scavenging. The authors propose that TQ-6 might mitigate neurodegenerative pathology by inhibiting the NF-κB-mediated downstream pathway (iNOS and COX-2) and enhancing Nrf2/HO-1 signaling molecules in microglia.

Protective role of Salvia miltiorrhiza Polysaccharides on Florfenicol Induced Oxidative and Apoptotic Injury of Liver in Broilers

2021 ◽  
Author(s):  
Xiao Wang ◽  
Yuqing Cui ◽  
Chao Han ◽  
Yumeng Geng ◽  
Di Zhang ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Liver Injury ◽  
Protein Expression ◽  
Liver Tissue ◽  
Salvia Miltiorrhiza ◽  
Protective Role ◽  
Heme Oxygenase 1 ◽  
Related Factor ◽  
Mrna And Protein Expression ◽  
Liver Tissues

Abstract Salvia miltiorrhiza Polysaccharides (SMPs) can alleviate liver injury in mice, but there are few reports on liver injury of broilers, especially the liver injury caused by antibiotics. To explore the hepatoprotective effects of SMPs against florfenicol (FFC) induced broilers liver injury, the broilers were treated with FFC and SMPs. The results showed SMPs could significantly inhibit the decrease of weight gain and the increase of liver index induced by FFC (P < 0.05). SMPs could significantly reduce the contents of Alanine aminotransferase (ALT) and Aspartate aminotransferase (AST) in serum and the malondialdehyde (MDA), nitric oxide (NO) and inducible nitric oxide synthase (iNOS) in liver tissues (P < 0.05), also significantly increased the content of total protein (TP) in serum and superoxide dismutase (SOD), catalase (CAT) in liver tissues (P < 0.05). QPCR and western bolt results showed that SMPs significantly increased the mRNA and protein expression of cytochrome P4501A1 (CYP1A1), cytochrome P4502H1 (CYP2H1), nuclear factor-erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1) and NAD(P)H dehydrogenase quinone-1 (NQO-1) in liver tissue, also significantly reduced the rate of hepatocyte apoptosis and the mRNA and protein expression of p53, cytochrome-C (CytC), caspase-3 in liver tissue (P < 0.05). The results demonstrated that SMPs can inhibit the oxidative stress in hepatocytes by regulating the related proteins in Nrf2 pathway, thereby reducing the apoptosis of hepatocytes, and protecting liver injury.

scholarly journals KCHO-1, a Novel Antineuroinflammatory Agent, Inhibits Lipopolysaccharide-Induced Neuroinflammatory Responses through Nrf2-Mediated Heme Oxygenase-1 Expression in Mouse BV2 Microglia Cells

2014 ◽  
Vol 2014 ◽  
pp. 1-11 ◽  
Author(s):  
Dong-Sung Lee ◽  
Wonmin Ko ◽  
Chi-Su Yoon ◽  
Dong-Cheol Kim ◽  
Jinju Yun ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Neurodegenerative Diseases ◽  
Heme Oxygenase ◽  
Nuclear Factor Kappa B ◽  
Heme Oxygenase 1 ◽  
Related Factor ◽  
Nuclear Factor ◽  
Nuclear Factor Kappa ◽  
Bv2 Microglia ◽  
Cox 2

The brain is vulnerable to oxidative stress and inflammation that can occur as a result of aging or neurodegenerative diseases. Our work has sought to identify natural products that regulate heme oxygenase (HO)-1 and to determine their mechanism of action in neurodegenerative diseases. KCHO-1 is a novel herbal therapeutic containing 30% ethanol (EtOH) extracts from nine plants. In this study, we investigated the antineuroinflammatory effects of KCHO-1 in lipopolysaccharide- (LPS-) treated mouse BV2 microglia. KCHO-1 inhibited the protein expression of inducible nitric oxide synthase (iNOS), iNOS-derived nitric oxide (NO), cyclooxygenase- (COX-) 2, and COX-2-derived prostaglandin E2 (PGE2) in LPS-stimulated BV2 microglia. It also reduced tumor necrosis factor-α(TNF-α), interleukin-1β(IL-1β), and IL-6 production. This effect was correlated with the suppression of inhibitor of nuclear factor kappa B-α(IκB-α) phosphorylation and degradation and nuclear factor kappa B (NF-κB) translocation and DNA binding. Additionally, KCHO-1 upregulated HO-1 expression by promoting nuclear translocation of nuclear factor E2-related factor 2 (Nrf2) in mouse BV2 microglia. Tin protoporphyrin (SnPP), an HO activity inhibitor, was used to verify the inhibitory effects of KCHO-1 on proinflammatory mediators and proteins associated with HO-1 expression. Our data suggest that KCHO-1 has therapeutic potential in neurodegenerative diseases caused by neuroinflammation.

scholarly journals Antineuroinflammatory and Neuroprotective Effects of Gyejibokryeong-Hwan in Lipopolysaccharide-Stimulated BV2 Microglia

2019 ◽  
Vol 2019 ◽  
pp. 1-14 ◽  
Author(s):  
Bo-Kyung Park ◽  
Young Hwa Kim ◽  
Yu Ri Kim ◽  
Jeong June Choi ◽  
Changsop Yang ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Mitogen Activated Protein Kinase ◽  
Heme Oxygenase 1 ◽  
Related Factor ◽  
Dependent Manner ◽  
Nuclear Factor ◽  
Neuroprotective Effects ◽  
Bv2 Cells ◽  
Bv2 Microglia ◽  
Anti Inflammatory

Microglia, the central nervous system’s innate immune cells, mediate neuroinflammation and are implicated in a variety of neuropathologies. The present study investigated the antineuroinflammatory and neuroprotective effects of Gyejibokryeong-hwan (GBH), a traditional Korean medicine, in lipopolysaccharide- (LPS-) stimulated murine BV2 microglia. BV2 cells were pretreated with GBH, fluoxetine (FXT), or amitriptyline (AMT) for 1 h and then stimulated with LPS (100 ng/mL). The expression levels of nitric oxide (NO), cytokines, and chemokines were determined by the Griess method, ELISA, or real-time PCR. Western blotting was used to measure various transcription factors and mitogen activated protein kinase (MAPK) and phosphatidylinositol 3-kinase (PI3K)/Akt activity. GBH significantly reduced the levels of NO, inducible nitric oxide synthase (iNOS), cyclooxygenase- (COX-) 2, tumor necrosis factor- (TNF-) α, interleukin- (IL-) 1β, IL-6, macrophage inhibitory protein- (MIP-) 1α, macrophage chemoattractant protein- (MCP-) 1, and IFN-γ inducible protein- (IP-) 10, regulated upon activation normal T cell expressed sequence (RANTES) in a dose-dependent manner. Expression of nuclear factor- (NF-) κB p65 was significantly decreased and phosphorylation of extracellular signal-regulated kinase (Erk), c-Jun NH2-terminal kinase (JNK), and PI3K/Akt by GBH, but not p38 MAPK, was decreased. Furthermore, production of anti-inflammatory cytokine IL-10 was increased and Heme oxygenase-1 (HO-1) was upregulated via the nuclear factor-E2-related factor 2 (NRF2)/cAMP response element-binding protein (CREB) pathway, collectively indicating the neuroprotective effects of GBH. We concluded that GBH may suppress neuroinflammatory responses by inhibiting NF-κB activation and upregulating the neuroprotective factor, HO-1. These results suggest that GBH has potential as anti-inflammatory and neuroprotective agents against microglia-mediated neuroinflammatory disorders.

scholarly journals Total Flavonoids of Crocus sativus Petals Release tert-Butyl Hydroperoxide-Induced Oxidative Stress in BRL-3A Cells

2021 ◽  
Vol 2021 ◽  
pp. 1-15
Author(s):  
Hong Ye ◽  
Juan Luo ◽  
Dongmei Hu ◽  
Shuting Yang ◽  
Aolai Zhang ◽  
...  
Keyword(s):  
Superoxide Dismutase ◽  
Antioxidant Capacity ◽  
B Cell Lymphoma ◽  
Crocus Sativus ◽  
Heme Oxygenase 1 ◽  
Related Factor ◽  
Nuclear Factor ◽  
Butyl Hydroperoxide ◽  
Tert Butyl ◽  
Tert Butyl Hydroperoxide

Antioxidant and hepatoprotective activities in vitro of saffron petals were examined in this study for better utilizing saffron (Crocus sativus L.) biowaste. Using the DPPH and ABTS radical scavenging method, we compared the antioxidant activity and the content of total flavonoid extracts from petals (TFESP), stamens (TFESS), and both saffron petals and stamens (TFEMS). The results showed that the antioxidant capacity and the flavonoid content of TFESP were higher than those of TFESS and TFEMS. Then, the hepatoprotective activity of TFESP was determined, and the silymarin was used as a positive control. The main components of TFESP were analysed by ultrahigh performance liquid chromatography (UPLC) photodiode array (PDA)/mass spectrometry (MS) and nuclear magnetic resonance (NMR). The result showed that (1) TFESP could release oxidative liver injury induced by tert-butyl hydroperoxide (t-BHP). (2) TFESP could reduce the accumulation of reactive oxygen species (ROS); enhance the activity of superoxide dismutase (SOD), catalase (CAT), and glutathione (GSH); and then improve the total antioxidant capacity (T-AOC) in BRL-3A cells. (3) TFESP could enhance the expression of B-cell lymphoma-2 (BCL-2) and decrease the expression of caspase-3 and caspase-9; increase the expression of Kelch-like ECH-associated protein-1 (Keap-1), nuclear factor, erythroid 2-related factor 2 (Nrf2), superoxide dismutase, and heme oxygenase 1 (HO-1); and downregulate inducible nitric oxide synthase (INOS), interleukin-6 (IL-6), and nuclear factor kappa B-9 (NF-κB-9). (4) The main hepatoprotective component of TFESP was identified as kaempferol-3-o-sophoroside. The mechanism may be that kaempferol-3-o-sophoroside can protect t-BHP-induced cell injury by regulating the expression of antioxidant, antiapoptotic, and anti-inflammatory genes. Thus, saffron petals are a potential hepatoprotective resource worthy of development.

scholarly journals Preventive Effect of Lactobacillus Plantarum HFY15 on Oxidative Damage and Acute Liver Injury Induced by Carbon Tetrachloride (CCl 4 ) in Mice

2021 ◽  
Author(s):  
Xingyao Long ◽  
Pan Wang ◽  
Yujing Zhou ◽  
Qiang Wang ◽  
Lixuan Ren ◽  
...  
Keyword(s):  
Carbon Tetrachloride ◽  
Liver Injury ◽  
Oxidative Damage ◽  
Lactobacillus Plantarum ◽  
Acute Liver Injury ◽  
Animal Experiments ◽  
B Cell Lymphoma ◽  
Related Factor ◽  
Preventive Effect ◽  
Antioxidant Genes

Abstract BackgroundCarbon tetrachloride (CCl4) is a widely used hepatic toxin that causes acute liver injury through pathological mechanisms such as oxidative stress, inflammation, and apoptosis. In this experiment, mice were treated with Lactobacillus plantarum (LP) HFY15, silymarin, and Lactobacillus delbruechii subsp. bulgaricus (LDSB) for two weeks, and intraperitoneal injection of CCl4-induced acute liver injury to study the preventive effect of LP-HFY on CCl4-induced acute liver injury, especially in oxidative damage. ResultsThe survival rate of LP-HFY15 in artificial gastric juice is 92.1%, and the growth efficiency in bile salt is 78.8%. Animal experiments show that LP-HFY15 reduces the liver index of mice, reduces the activity of alanine aminotransferase (ALT) and aspartate aminotransferase (AST), the content of triglycerides (TG), malondialdehyde (MDA) and reactive oxygen species (ROS) in the serum of mice. LP-HFY15 also increased the antioxidant genes, such as nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase (HO-1), NAD(P)H:quinone oxidoreductase (NQO1), and increases the activity of superoxide dismutation (SOD), catalase (CAT), and glutathione (GSH) in the serum and gene level. At the same time, LP-HFY15 reduced the levels of cytokines IL-6, TNF-α, and IFN-γ in the serum and liver, increased antiapoptosis gene B-cell lymphoma-2 (Bcl-2) expression in the liver of mice, and inhibit the expression of proapoptotic genes Bcl-2-associated X (Bax) and Caspase-3. ConclusionsCompared with LDSB, LP-HFY15 has a greater alleviating effect on the liver injury caused by CCl4. These findings demonstrate that LP-HFY15 has great potential and research value in the future as a food supplement for preventing acute liver damage.

scholarly journals The Antioxidant, Anti-Inflammatory, and Neuroprotective Properties of the Synthetic Chalcone Derivative AN07

Molecules ◽  
2020 ◽  
Vol 25 (12) ◽  
pp. 2907 ◽  
Author(s):  
Yih-Fung Chen ◽  
Sheng-Nan Wu ◽  
Jia-Mao Gao ◽  
Zhi-Yao Liao ◽  
Yu-Ting Tseng ◽  
...  
Keyword(s):  
B Cell Lymphoma ◽  
Biologically Active ◽  
Heme Oxygenase 1 ◽  
Raw 264.7 ◽  
Related Factor ◽  
Nuclear Factor ◽  
Lim Kinase ◽  
Raw 264.7 Macrophages ◽  
Cox 2 ◽  
Anti Inflammatory

Chalcones belong to a class of biologically active polyphenolic natural products. As a result of their simple chemical nature, they are easily synthesized and show a variety of promising biological activities. 2-Hydroxy-4′-methoxychalcone (AN07) is a synthetic chalcone derivate with potential anti-atherosclerosis effects. In this study, we demonstrated the novel antioxidant, anti-inflammatory, and neuroprotective effects of AN07. In RAW 264.7 macrophages, AN07 attenuated lipopolysaccharide (LPS)-induced elevations in reactive oxygen species (ROS) level and oxidative stress via down-regulating gp91phox expression and stimulating the antioxidant system of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) pathways, which were accompanied by increased glutathione (GSH) levels. Additionally, AN07 attenuated LPS-induced inflammatory factors, including NO, inducible NO synthase (iNOS), cyclooxygenase-2 (COX-2), and phosphorylated inhibitor of nuclear factor kappa B-alpha (p-IκBα) in RAW 264.7 macrophages. However, the effects of AN07 on promoting nuclear Nrf2 levels and decreasing COX-2 expressions were significantly abrogated by the peroxisome proliferator-activated receptor-γ (PPARγ) antagonist GW9662. In human dopaminergic SH-SY5Y cells treated with or without methylglyoxal (MG), a toxic endogenous by-product of glycolysis, AN07 up-regulated neurotrophic signals including insulin-like growth factor 1 receptor (IGF-1R), p-Akt, p-GSK3β, glucagon-like peptide 1 receptor (GLP-1R), and brain-derived neurotrophic factor (BDNF). AN07 attenuated MG-induced apoptosis by up-regulating the B-cell lymphoma 2 (Bcl-2) protein and down-regulating the cytosolic expression of cytochrome c. AN07 also attenuated MG-induced neurite damage via down-regulating the Rho-associated protein kinase 2 (ROCK2)/phosphorylated LIM kinase 1 (p-LIMK1) pathway. Moreover, AN07 ameliorated the MG-induced down-regulation of neuroprotective Parkinsonism-associated proteins parkin, pink1, and DJ-1. These findings suggest that AN07 possesses the potentials to be an anti-inflammatory, antioxidant, and neuroprotective agent

scholarly journals Protective Effect of Glutathione against Oxidative Stress-induced Cytotoxicity in RAW 264.7 Macrophages through Activating the Nuclear Factor Erythroid 2-Related Factor-2/Heme Oxygenase-1 Pathway

Antioxidants ◽  
2019 ◽  
Vol 8 (4) ◽  
pp. 82 ◽  
Author(s):  
Da Kwon ◽  
Hee-Jae Cha ◽  
Hyesook Lee ◽  
Su-Hyun Hong ◽  
Cheol Park ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Dna Damage ◽  
Protective Effect ◽  
Heme Oxygenase ◽  
Raw 264.7 Cells ◽  
Heme Oxygenase 1 ◽  
Raw 264.7 ◽  
Related Factor ◽  
Nuclear Factor ◽  
Raw 264.7 Macrophages

Reactive oxygen species (ROS), products of oxidative stress, contribute to the initiation and progression of the pathogenesis of various diseases. Glutathione is a major antioxidant that can help prevent the process through the removal of ROS. The aim of this study was to evaluate the protective effect of glutathione on ROS-mediated DNA damage and apoptosis caused by hydrogen peroxide, H2O2, in RAW 264.7 macrophages and to investigate the role of the nuclear factor erythroid 2-related factor-2 (Nrf2)/heme oxygenase-1 (HO-1) signaling pathway. The results showed that the decrease in the survival rate of RAW 264.7 cells treated with H2O2 was due to the induction of DNA damage and apoptosis accompanied by the increased production of ROS. However, H2O2-induced cytotoxicity and ROS generation were significantly reversed by glutathione. In addition, the H2O2-induced loss of mitochondrial membrane potential was related to a decrease in adenosine triphosphate (ATP) levels, and these changes were also significantly attenuated in the presence of glutathione. These protective actions were accompanied by a increase in the expression rate of B-cell lymphoma-2 (Bcl-2)/Bcl-2-associated X protein (Bax) and poly(ADP-ribose) polymerase cleavage by the inactivation of caspase-3. Moreover, glutathione-mediated cytoprotective properties were associated with an increased activation of Nrf2 and expression of HO-1; however, the inhibition of the HO-1 function using an HO-1 specific inhibitor, zinc protoporphyrin IX, significantly weakened the cytoprotective effects of glutathione. Collectively, the results demonstrate that the exogenous administration of glutathione is able to protect RAW 264.7 cells against oxidative stress-induced mitochondria-mediated apoptosis along with the activity of the Nrf2/HO-1 signaling pathway.

scholarly journals Dendrobium officinale Flower Extraction Mitigates Alcohol-Induced Liver Injury in Mice: Role of Antisteatosis, Antioxidative, and Anti-Inflammatory

2020 ◽  
Vol 2020 ◽  
pp. 1-12
Author(s):  
Yu-Lin Wu ◽  
Si-Han Huang ◽  
Chun-Mei He ◽  
Bo Qiu ◽  
Jing-Jing Liu ◽  
...  
Keyword(s):  
Liver Injury ◽  
Protective Effect ◽  
Serum Levels ◽  
Dendrobium Officinale ◽  
Heme Oxygenase 1 ◽  
Related Factor ◽  
Nuclear Factor ◽  
Quinone Oxidoreductase ◽  
Inflammatory Infiltration ◽  
Anti Inflammatory

The study aimed to evaluate the protective effect of Dendrobium officinale flower extraction (DOFE) on alcohol-induced liver injury and its probable mechanisms in mice. The chemical composition of DOFE was performed via UPLC/MS. Male Kunming mice were used to establish alcohol-induced liver injury models by oral gavage of 56% alcohol. Results showed that DOFE dramatically attenuated the increased serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), total cholesterol (TC), and triacylglycerol (TG). Meanwhile, hematoxylin and eosin and Oil Red O staining showed that DOFE attenuated degeneration, inflammatory infiltration, and lipid droplet accumulation. DOFE was also found to suppress the activity of malonaldehyde (MDA) and enhanced the level of glutathione (GSH) and the activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase (CAT) in the liver. The protection of DOFE against oxidative stress was associated with the downregulation of hepatic cytochrome P450 2E1 (CYP2E1) and upregulation of nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), and NAD(P)H quinone oxidoreductase l (NQO1). Additionally, DOFE suppressed inflammation via downregulating Toll-like receptor-4 (TLR-4) and nuclear factor kappa-B P65 (NF-κB P65). Thus, DOFE exhibited a significant protective effect against alcohol-induced liver injury through its antisteatosis, antioxidative, and anti-inflammatory effect.

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