scholarly journals Zerumbone Protects against Carbon Tetrachloride (CCl4)-Induced Acute Liver Injury in Mice via Inhibiting Oxidative Stress and the Inflammatory Response: Involving the TLR4/NF-κB/COX-2 Pathway

Molecules ◽  
2019 ◽  
Vol 24 (10) ◽  
pp. 1964 ◽  
Author(s):  
Meilin Wang ◽  
Jingling Niu ◽  
Lina Ou ◽  
Bo Deng ◽  
Yingyi Wang ◽  
...  
Keyword(s):  
Liver Injury ◽  
Acute Liver Injury ◽  
Hepatoprotective Effect ◽  
Histopathological Analysis ◽  
Potential Candidate ◽  
Dependent Manner ◽  
Necrosis Factor Alpha ◽  
Cellular Models ◽  
Cox 2 ◽  
Anti Inflammatory

The natural compound Zerumbone (hereinafter referred to as ZER), a monocyclic sesquiterpenoid, has been reported to possess many pharmacological properties, including antioxidant and anti-inflammatory properties. This study aimed to investigate the underlying mechanism of ZER against acute liver injury (ALI) in CCl4-induced mice models. ICR mice were pretreated intraperitoneally with ZER for five days, then received a CCl4 injection two hours after the last ZER administration and were sacrificed 24 h later. Examination of serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities and the histopathological analysis confirmed the hepatoprotective effect of ZER. Biochemical assays revealed that ZER pretreatment recovered the activities of antioxidant enzymes superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), restored the glutathione (GSH) reservoir, and reduced the production of malondialdehyde (MDA), all in a dose-dependent manner. Furthermore, administration of ZER in vivo reduced the release amounts of pro-inflammatory cytokines interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α) and inhibited the increased protein levels of Toll-like receptor 4 (TLR4), nuclear factor-kappaB (NF-κB) p-p65, and cyclooxygenase (COX-2). Further studies in lipopolysaccharide (LPS)-induced Raw264.7 inflammatory cellular models verified that ZER could inhibit inflammation via inactivating the TLR4/NF-κB/COX-2 pathway. Thus, our study indicated that ZER exhibited a hepatoprotective effect against ALI through its antioxidant and anti-inflammatory activities and the possible mechanism might be mediated by the TLR4/NF-κB/COX-2 pathway. Collectively, our studies indicate ZER could be a potential candidate for chemical liver injury treatment.

scholarly journals Aloperine attenuates carbon tetrachloride-induced mouse hepatic injury via Nrf2/HO-1 pathway

2020 ◽  
Vol 19 (5) ◽  
pp. 983-988
Author(s):  
Rui Xiong ◽  
Shuzhong Shan ◽  
Xiaoming Wang ◽  
Xiaowen Zhang ◽  
Haixia Yu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Carbon Tetrachloride ◽  
Liver Injury ◽  
Hepatic Injury ◽  
Acute Liver Injury ◽  
Control Group ◽  
Histopathological Analysis ◽  
Dependent Manner ◽  
Oxidative Stress Biomarkers ◽  
Cox 2

Purpose: To investigate whether aloperine pretreatment ameliorates acute liver injury in carbon tetrachloride (CCl4)-treated mice.Methods: Mice were injected with CCl4 and orally administered aloperine. Blood samples and liver tissues were used for histopathological and biochemical analyses, respectively. Protein expression levels were determined by western blotting.Results: Histopathological analysis indicate that aloperine pretreatment significantly alleviated CCl4- induced mouse hepatic injury. CCl4 treatment induced the upregulation of aspartate aminotransferase (AST), alkaline phosphatase (ALP), alanine amino transferase (ALT), and total bilirubin (p < 0.05). However, these alterations were significantly inhibited by aloperine treatment. Moreover, aloperine pretreatment markedly decreased (p < 0.05) the CCl4-induced expression of oxidative stress biomarkers, including malondrialdeline (MDA), glutathione (GSH), catalase (CAT), and  superoxide dismutase (SOD). Compared to the control group, the protein levels of Nrf2, HO-1, iNOS, and COX-2 were significantly increased in the CCl4 group, while Nrf2 and HO-1 were upregulated. Furthermore, iNOS and COX-2 were downregulated in mouse liver in CCl4 + aloperine group compared to CCl4 group in a concentration-dependent manner (p < 0.05).Conclusion: Aloperine pretreatment appears to markedly upregulate Nrf2 and HO-1 and downregulate iNOS and COX-2 to suppress hepatic injury in mice. Thus, aloperine is a promising treatment for acute liver injury. Keywords: Hepatic injury, Aloperine, Oxidative stress, Nrf2/HO-1 pathway

scholarly journals Anti-Inflammatory Activity of the Active Compounds of Sanguisorbae Radix In Macrophages and in Vivo Toxicity Evaluation in Zebrafish

Cosmetics ◽  
2019 ◽  
Vol 6 (4) ◽  
pp. 68
Author(s):  
Young-Ah Jang ◽  
Yong Hur ◽  
Jin-Tae Lee
Keyword(s):  
Target Genes ◽  
Inflammatory Activity ◽  
Dependent Manner ◽  
Active Components ◽  
Necrosis Factor Alpha ◽  
In Vivo Toxicity ◽  
Cox 2 ◽  
Anti Inflammatory ◽  
Sanguisorbae Radix

Sanguisorbae Radix (SR) is the root of the Sanguisorba officinalis L., a plant native to Asian countries and used in traditional medicine. We isolated the active components of SR and investigated their anti-inflammatory potential. Quercetin (QC), (+)-catechin (CC), and gallic acid (GA) were isolated from acetone extracts of SR. To elucidate the molecular mechanism by which these compounds suppress inflammation, we analyzed the transcriptional up-regulation of inflammatory mediators, such as nuclear factor-kappa B (NF-κB) and its target genes, inducible NOS (iNOS), and cyclooxygenase (COX)-2, in lipopolysaccharide (LPS)-stimulated macrophage RAW264.7 cells. Notably, QC, CC, and GA were found to inhibit the production of nitric oxide, tumor necrosis factor-alpha, and prostaglandin in a dose-dependent manner. Western blot results indicate that the compounds decreased the expression of iNOS and COX-2 proteins. Furthermore, the compounds decreased phosphorylation of IKK, IκB, ERK, p-38, and JNK proteins in LPS-induced cells. The results support the notion that QC, CC, and GA can potently inhibit the inflammatory response, with QC showing the highest anti-inflammatory activity. In in vivo toxicity studies in zebrafish (Danio rerio), QC showed no toxicity up to 25 μg/mL. Therefore, QC has non-toxic potential as a skin anti-inflammatory biomaterial.

scholarly journals Antinociceptive and Anti-Inflammatory Effects of Total Alkaloid Extract fromFumaria capreolata

2015 ◽  
Vol 2015 ◽  
pp. 1-7 ◽  
Author(s):  
Noureddine Bribi ◽  
Francesca Algieri ◽  
Alba Rodriguez-Nogales ◽  
Jose Garrido-Mesa ◽  
Teresa Vezza ◽  
...  
Keyword(s):  
Acetic Acid ◽  
Inflammatory Diseases ◽  
Potential Candidate ◽  
Dependent Manner ◽  
Proinflammatory Mediators ◽  
Total Alkaloids ◽  
Aerial Parts ◽  
Cox 2 ◽  
Anti Inflammatory ◽  
Fumaria Capreolata

Fumaria capreolatais used in traditional medicine in North Africa for its gastrointestinal and anti-inflammatory activities. The present study investigates the effects of total alkaloids extracted from the aerial parts ofFumaria capreolata(AFC) on LPS-induced production of proinflammatory mediators (IL-6, IL-1β, iNOS, TNF-α, COX-2, and MIP-2) in RAW264.7 cells. AFC significantly reduced the inflammatory response inhibiting the production of nitric oxide (NO) and IL-6 in a dose-dependent manner, without affecting the viability of cells, and downregulated mRNA expression of proinflammatory key players: IL-6, IL-1β, iNOS, TNF-α, and COX-2. AFC antinociceptive and anti-inflammatory properties were also evaluated on the acetic acid- and formalin-induced pain models in mice. AFC oral administration significantly inhibited acetic acid-induced writhes and reduced formalin-induced paw licking time. Therefore, AFC may be a potential candidate for the treatment of inflammatory diseases, such as colitis and arthritis.

scholarly journals Lemon Balm and Dandelion Leaf Extracts Synergistically Protect against Carbon Tetrachloride-Induced Acute Liver Injury in Mice

2021 ◽  
Vol 11 (1) ◽  
pp. 390
Author(s):  
Beom-Rak Choi ◽  
Il-Je Cho ◽  
Su-Jin Jung ◽  
Jae-Kwang Kim ◽  
Dae-Geon Lee ◽  
...  
Keyword(s):  
Carbon Tetrachloride ◽  
Liver Injury ◽  
Acute Liver Injury ◽  
Antioxidant Activities ◽  
Body Weight Gain ◽  
Histopathological Analysis ◽  
Related Factor ◽  
Mrna Levels ◽  
Protective Effects ◽  
Lemon Balm

Lemon balm and dandelion are commonly used medicinal herbs exhibiting numerous pharmacological activities that are beneficial for human health. In this study, we explored the protective effects of a 2:1 (w/w) mixture of lemon balm and dandelion extracts (MLD) on carbon tetrachloride (CCl4)-induced acute liver injury in mice. CCl4 (0.5 mL/kg; i.p.) injection inhibited body weight gain and increased relative liver weight. Pre-administration of MLD (50–200 mg/kg) for 7 days prevented these CCl4-mediated changes. In addition, histopathological analysis revealed that MLD synergistically alleviated CCl4-mediated hepatocyte degeneration and infiltration of inflammatory cells. MLD decreased serum aspartate aminotransferase and alanine transferase activities and reduced the number of liver cells that stained positive for cleaved caspase-3 and cleaved poly(ADP-ribose) polymerase, suggesting that MLD protects against CCl4-induced hepatic damage via the inhibition of apoptosis. Moreover, MLD attenuated CCl4-mediated lipid peroxidation and protein nitrosylation by restoring impaired hepatic nuclear factor erythroid 2-related factor 2 mRNA levels and its dependent antioxidant activities. Furthermore, MLD synergistically decreased mRNA and protein levels of tumor necrosis factor-α, interleukin-1β, and interleukin-6 in the liver. Together, these results suggest that MLD has potential for preventing acute liver injury by inhibiting apoptosis, oxidative stress, and inflammation.

scholarly journals Constitutive expression of cyclo-oxygenase 2 transgene in hepatocytes protects against liver injury

2008 ◽  
Vol 416 (3) ◽  
pp. 337-346 ◽  
Author(s):  
Rafael Mayoral ◽  
Belen Mollá ◽  
Juana Maria Flores ◽  
Lisardo Boscá ◽  
Marta Casado ◽  
...  
Keyword(s):  
Liver Injury ◽  
Transgenic Mice ◽  
Genetic Model ◽  
Acute Liver Injury ◽  
Constitutive Expression ◽  
Transgenic Animals ◽  
Hepatocyte Proliferation ◽  
Nuclear Antigen ◽  
Cox 2 ◽  
Inflammatory Profile

The effect of COX (cyclo-oxygenase)-2-dependent PGs (prostaglandins) in acute liver injury has been investigated in transgenic mice that express human COX-2 in hepatocytes. We have used three well-established models of liver injury: in LPS (lipopolysaccharide) injury in D-GalN (D-galactosamine)-preconditioned mice; in the hepatitis induced by ConA (concanavalin A); and in the proliferation of hepatocytes in regenerating liver after PH (partial hepatectomy). The results from the present study demonstrate that PG synthesis in hepatocytes decreases the susceptibility to LPS/D-GalN or ConA-induced liver injury as deduced by significantly lower levels of the pro-inflammatory profile and plasmatic aminotransferases in transgenic mice, an effect suppressed by COX-2-selective inhibitors. These Tg (transgenic) animals express higher levels of anti-apoptotic proteins and exhibit activation of proteins implicated in cell survival, such as Akt and AMP kinase after injury. The resistance to LPS/D-GalN-induced liver apoptosis involves an impairment of procaspase 3 and 8 activation. Protection against ConA-induced injury implies a significant reduction in necrosis. Moreover, hepatocyte commitment to start replication is anticipated in Tg mice after PH, due to the expression of PCNA (proliferating cell nuclear antigen), cyclin D1 and E. These results show, in a genetic model, that tissue-specific COX-2-dependent PGs exert an efficient protection against acute liver injury by an antiapoptotic/antinecrotic effect and by accelerated early hepatocyte proliferation.

scholarly journals The role of non-steroidal anti-inflammatory drugs in acute liver injury.

BMJ ◽  
1992 ◽  
Vol 305 (6858) ◽  
pp. 865-868 ◽  
Author(s):  
L. A. Garcia Rodriguez ◽  
S. Perez Gutthann ◽  
A. M. Walker ◽  
L. Lueck
Keyword(s):  
Liver Injury ◽  
Acute Liver Injury ◽  
Inflammatory Drugs ◽  
Anti Inflammatory

scholarly journals Dynamic Evaluation of Compound Ento-PB for the Repair of Mucosal Ulcer in Dogs With Acetic Acid-induced Experimental Colitis 

2020 ◽  
Author(s):  
Jin-hu Chen ◽  
Jian-ting Zhao ◽  
Zheng-yong Yu ◽  
Yi-hao Che ◽  
Yu-jia Wang ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Acetic Acid ◽  
Inflammatory Cytokines ◽  
Mucosal Healing ◽  
Dynamic Monitoring ◽  
Enzyme Linked Immunosorbent Assay ◽  
Dependent Manner ◽  
Expression Levels ◽  
Cox 2 ◽  
Anti Inflammatory

Abstract Background: Mucosal inflammation and ulcer play important roles in the pathogenesis of ulcerative colitis. As as traditional Chinese medicine compound composed of Periplaneta americana and Taraxacum mongolicum, Ento-PB is always prescribed for the treatment of ulcer and inflammatory diseases. As for the significant role of P. americana in terms of promoting mucosal healing, the compatibility of the anti-inflammatory drug T. mongolicum may enable Ento-PB to simultaneously play anti-inflammatory and promote mucosal healing effects on the treatment of UC. Therefore, this study aimed to evaluate the therapeutic potential and possible mechanism of Ento-PB for UC by establishing an acetic acid-induced colitis model in dogs.Methods: Preliminary identification to the chemical components of compound Ento-PB was carried out through high performance liquid chromatography. A cross-bred dogs model of acetic acid-induced ulcerative colitis was established to evaluate the efficacy of compound Ento-PB. The expression levels of inflammatory cytokines C-reactive protein (CRP), inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and interleukin-10 (IL-10) in plasma were measured by carrying out enzyme-linked immunosorbent assay (ELISA).Results: With the extension of treatment time, Ento-PB could effectively improve clinical symptoms of UC cross-bred dogs. Colonoscopy displayed that mucosal redness, swelling and congestion decreased gradually, and obviously repaired after mucosal injury. The intestinal texture was gradually clear, and the colonoscopy score gradually reduced. Histopathological examination revealed that the structure of colon was restored significantly, the infiltration of inflammatory cells was reduced, and the histological score was remarkably reduced. At the same time, the results of dynamic monitoring of inflammatory cytokines in plasma proved that Ento-PB can gradually down-regulate the activity of CRP, iNOS and COX-2, reduce the expression levels of inflammatory cytokines TNF-α and IL-1β, and gradually restore anti-inflammatory and the expression level of cytokine IL-10.Conclusions: Ento-PB reduces the level of pro-inflammatory cytokines in a dose- and time-dependent manner and inflammation, improves colon tissue lesions and the repair of intestinal mucosa after injury, and effectively increases acetic acid-induced colon inflammation in UC cross-bred dogs.

scholarly journals Hepatoprotective Effects of Heracleum candicans Against Carbon Tetrachloride-Induced Acute Liver Injury in Rats

Dose-Response ◽  
2021 ◽  
Vol 19 (3) ◽  
pp. 155932582110295
Author(s):  
Jie Li ◽  
Dan Song ◽  
Bintao Zhang ◽  
Jinwei Guo ◽  
Wenping Li ◽  
...  
Keyword(s):  
Carbon Tetrachloride ◽  
Liver Injury ◽  
Acute Liver Injury ◽  
Neutrophil Infiltration ◽  
Antioxidant Enzyme Activity ◽  
Necrosis Factor Alpha ◽  
Heracleum Candicans ◽  
The Face ◽  
Factor Alpha ◽  
Necrosis Factor

Purpose: To determine the hepatoprotective mechanisms of Heracleum candicans in rats with acute liver injury induced by carbon tetrachloride (CCl4). Methods: Rats were intragastrically administered H candicans twice a day for 14 consecutive days and were intraperitoneally challenged with CCl4. Alanine aminotransferase and aspartate aminotransferase were measured to indicate liver injury. Malondialdehyde antioxidant enzyme activity and tumor necrosis factor-alpha and interleukin 6 secretion were measured as liver injury indicators. Histopathological tests were conducted to determine whether H candicans ameliorated liver injury. Results: CCl4-induced liver injury led to significant increases in liver injury biochemical indicators transaminase and malondialdehyde activities. H candicans pretreatments inhibited these increases. Pathological sections in pretreated samples exhibited reduced vacuole formation, neutrophil infiltration, and necrosis. Conclusion: H candicans increases the antioxidant capacity of the liver and maintains hepatocyte function in the face of CCl4-induced injury.

scholarly journals Exosome and Melatonin Additively Attenuates Inflammation by Transferring miR-34a, miR-124, and miR-135b

2020 ◽  
Vol 2020 ◽  
pp. 1-9
Author(s):  
June Seok Heo ◽  
Ja-Yun Lim ◽  
Dae Wui Yoon ◽  
Sangshin Pyo ◽  
Jinkwan Kim
Keyword(s):  
Ex Vivo ◽  
Inflammatory Diseases ◽  
Underlying Mechanism ◽  
M2 Macrophages ◽  
Necrosis Factor Alpha ◽  
Cellular Models ◽  
Positive Effects ◽  
Cell Based Therapy ◽  
Anti Inflammatory ◽  
Inflammatory Modulation

The positive effects of mesenchymal stem cells (MSCs) are primarily activated through molecular secretions known as paracrine activity, which regulates the function of various cell types including immune cells. Accumulating evidence shows that exosomes of soluble factors released from MSCs are potential alternative agents for stem cell-based therapy, although the exact underlying mechanism has not been elucidated. The purpose of this study was to evaluate the potential effects of exosomes produced by adipose-derived MSCs and to examine the changes in anti-inflammatory genes in concurrence with the polarization of M2 macrophages in cellular models ex vivo. Isolated exosomes were used to investigate the inflammatory modulation in pro-inflammatory cytokine-treated fibroblasts and THP-1 cells. The anti-inflammatory mRNA expression associated with M2 macrophages was significantly upregulated after exosome treatment in an interferon gamma and tumor necrosis factor alpha-treated inflammatory environment. Furthermore, melatonin-stimulated exosomes exerted superior anti-inflammatory modulation via exosomal miRNAs miR-34a, miR-124, and miR-135b, compared with exosomes. Our results indicate that melatonin-stimulated exosomes originating from adipose-derived MSCs are safe and efficient tools for regenerative medicine to treat inflammatory diseases.

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