Chronic inflammation has been considered as the main cause of chronic diseases. Zn has anti-inflammatory effects by decreasing the expression of inflammatory markers. The present systematic review and meta-analysis study aims to evaluate the impact of Zn supplementation on inflammation. PubMed (Medline), Scopus, Web of Science, and Embase databases were searched up to 10 December 2020. Controlled trials which have investigated the effects of Zn supplementation on serum/plasma levels of inflammatory cytokines in subjects aged >15 years were included. A pooled meta-analysis was performed using a random effect model. Sensitivity analysis was performed to determine the robustness of the observed effect sizes. A total of twelve studies was included in meta-analysis. Zn could decrease IL-6 levels (standardised mean difference (SMD) = −0·76 pg/ml; 95 % CI −1·28, −0·24; P = 0·004). There was no significant change in TNF-α (SMD = 0·42 pg/ml; 95 % CI −0·31, 1·16; P = 0·257) and IL-2 levels (SMD = 1·64 pg/ml; 95 % CI −1·31, 4·59; P = 0·277) following Zn supplementation. However, Zn could increase IL-2 significantly after the deletion of one arm in sensitivity analysis (SMD = 2·96 pg/ml; 95 % CI 2·03, 3·88; P < 0·05). Conclusively, Zn supplementation can decrease the IL-6 level. Zn increased IL-2 level after the sensitivity analysis. Zn supplementation has not ameliorative effects on TNF-α.

The present study investigated the effects of condensed tannins (CT) on intestinal immune function in on-growing grass carp (Ctenopharyngodon idella). A total of 540 healthy grass carp were fed six diets containing different levels of CT (0, 10·00, 20·00, 30·00, 40·00 and 50·00 g/kg diet) for 70 d and then challenged with Aeromonas hydrophila for 14 d. The results showed that, compared with the control group, dietary CT (1) induced intestinal histopathological lesions and aggravated enteritis; (2) decreased lysozyme and acid phosphatase activities, complement 3 (C3), C4 and IgM contents and down-regulated the Hepcidin, liver-expressed antimicrobial peptide (LEAP)-2A, LEAP-2B, Mucin2 and β-defensin-1 mRNA levels in the proximal intestine (PI), mid intestine (MI) and distal intestine (DI) (P < 0·05); (3) down-regulated the mRNA levels of anti-inflammatory cytokines transforming growth factor (TGF)-β1, TGF-β2 (not in MI and DI), IL-4/13A (not IL-4/13B), IL-10 and IL-11 partly correlated with target of rapamycin (TOR) signalling; and (4) up-regulated the mRNA levels of pro-inflammatory cytokines interferon-γ2, IL-1β, IL-6, IL-8 (not in PI), IL-12p35, IL-12p40, IL-15 and IL-17D partly related to NF-κB signalling in the intestine of on-growing grass carp. Overall, the results indicated that CT could impair the intestinal immune function, and its potential regulation mechanisms were partly associated with the TOR and NF-κB signalling pathways. Finally, based on the percentage weight gain and enteritis morbidity, the maximum allowable levels of CT for on-growing grass carp (232·22–890·11 g) were estimated to be 18·6 and 17·4 g/kg diet, respectively.

Subacute ruminal acidosis (SARA) can increase the level of inflammation and induce rumenitis in dairy cows. Berberine (BBR) is the major active component of Rhizoma Coptidis, which is a type of Chinese anti-inflammatory drug for gastrointestinal diseases. The purpose of this study was to investigate the anti-inflammatory effects of BBR on lipopolysaccharide (LPS)-stimulated rumen epithelial cells (REC) and the underlying molecular mechanisms. REC were cultured and stimulated with LPS in the presence or absence of different concentrations of BBR. The results showed that cell viability was not affected by BBR. Moreover, BBR markedly decreased the concentrations and mRNA expression of pro-inflammatory cytokines, including tumor necrosis factor-α, interleukin-1β, and interleukin-6 in the LPS-treated REC in a dose-dependent manner. Importantly, Western blotting analysis showed that BBR significantly suppressed the protein expression of toll-like receptor 4 (TLR4) and myeloid differentiation primary response protein (MyD88) and the phosphorylation of nuclear factor-κB (NF-κB), inhibitory kappa B (IκBα), p38 mitogen-activated protein kinase (MAPK), and c-Jun N-terminal kinase (JNK) in LPS-treated REC. Furthermore, the results of immunocytofluorescence showed that BBR significantly inhibited the nuclear translocation of NF-κB p65 induced by LPS treatment. In conclusion, the protective effects of BBR on LPS-induced inflammatory responses in REC may be due to its ability to suppress the TLR4-mediated NF-κB and MAPK signaling pathways. These findings suggest that BBR can be used as an anti-inflammatory drug to treat inflammation induced by SARA.

Obesity and particularly central obesity are the main risk factors of colon cancer. All intestinal cell populations including stem cells, their progenitors and differentiated colonocytes seem to be the origin of colorectal cancer. However, recent data support the role of differentiated cells as cancer origin especially during inflammation. Based on Yamanaka’s seminal work, re-expression of few transcription factors in terminally differentiated cells creates stemness properti'es. Although these transcription factors are involved in tumorigenesis, they are epigenetically repressed in adult tissues. We proposed that obesity might regulate methylation of stemness genes in colonocytes via inflammatory signalling. Obesity-associated inflammation was analysed using Western blot analysis of phospho-IκB (inhibitor of NF-κB). Methylation-sensitive high-resolution melting analysis was performed on colonic mucosal samples of twenty obese and twenty normal-weight men to analyse promoter methylation of POU5F1 (OCT4), NANOG, MYC and CDKN2A. TNF-treated HT-29 cells were used to recapitulate the effect of NF-κB activation on stemness genes methylation. Our results showed that colonic phosphorylation of IκB, as a signal of NF-κB activation, was higher in obese subjects compared with their normal-weight counterparts. Moreover, promoter methylation of NANOG was likely to be lower in obese subjects and correlated with central obesity. HT-29 cells incubated by TNF-α showed hypomethylation of POU5F1 and MYC genes in addition to the NANOG. These results suggest that obesity-induced inflammation might be involved in the regulation of DNA methylation of oncogenic genes such as NANOG in differentiated colonocytes and thus predispose them to later oncogenic alterations.

Elevated levels of blood interleukin-1β (IL-1β), interleukin-6 (IL-6) and tumour necrosis factor–α (TNF–α) increase insulin resistance and result in inflammation. It is not clear whether elevated blood level of acetoacetate (ACAC) and decreased blood level of glucose, which are the predominant characteristics of clinical biochemistry in ketotic dairy cows, increase proinflammatory cytokines and subsequent inflammation. The objective of this study was to test the hypothesis that ACAC and glucose activate the NF-κB signalling pathway to regulate cytokines expression in bovine hepatocytes. Bovine hepatocytes were cultured with ACAC (0–4·8 mm) and glucose (0–5·55 mm) with or without NF-κB inhibitor PDTC for 24 h. The secretion and mRNA levels of cytokines were determined by enzyme-linked immunosorbent assay (ELISA) and real-time fluorescence quantitative polymerase chain reaction (qRT-PCR). The NF-κB signalling pathway activation was evaluated by western blotting. Results showed that the secretion and expression of IL-1β, IL-6 and TNF-α increased in an ACAC dose-dependent manner. Additionally, there was an increase in the secretion and mRNA expression of these three cytokines in glucose treatment group, which increased significantly when the glucose concentrations exceed 3·33 mm. Furthermore, both ACAC and glucose upregulated NF-κB p65 protein expression and IκBα phosphorylation levels. However, these effects were reduced by PDTC. These results demonstrate that elevated levels of ACAC and glucose increase the synthesis and expression of proinflammatory factors by activating NF-κB signalling pathway in hepatocytes, which may contribute to inflammation injury in ketotic dairy cows.

Heat stress is characterised by reduced antioxidant status, and is one of the physiological alterations in response to exposure to higher temperatures in birds, which results in increased oxidative stress and immune suppression. The transcription entity nuclear factor-kappa light chain enhancer of B cells (NF-κB) controls the expression of genes involved in a number of physiological responses, including immune inflammatory responses, acute-phase inflammatory responses, oxidative stress responses, cell adhesion, differentiation, and apoptosis. The nuclear factor-2 erythroid related factor-2 (Nrf2), the redox-sensitive transcription factor, plays a key role in regulating induction of phase II detoxifying or antioxidant enzymes. Thus, activation of Nrf2 is considered to be an important molecular target of many anti-stressor agents. However, during heat stress conditions this regulation is disturbed offering an opportunity for therapeutic intervention. Heat stress is a condition in which the expression pattern of NF-κB and Nrf2 changes. To reduce the negative effects of heat, antioxidants are used in poultry diets for their anti-stress effects, associated with improved nutrient utilisation. For instance, lycopene, a powerful antioxidant, is particularly important because of its ability to quench reactive oxygen. This review focuses on the role of the NF-κB and Nrf2 in heat stress condition and summarises the therapeutic outcomes of lycopene in feed, targeted at the NF-κB and Nrf2 pathways in heat-stressed poultry.

High-fat, high-carbohydrate (HFHC) meals induce an inflammatory response in mononuclear cells (MNC). Here, we studied the interaction between metabolic and inflammatory signalling pathways by the measurement of postprandial effects of three different test meals on intracellular Akt, S6 kinase (S6K)/mammalian target of rapamycin and NF-κB signalling in human MNC. We recruited six healthy, lean individuals. Each individual ingested three different meals in the morning separated by at least 3 d: a HFHC meal; an oral lipid-tolerance test meal; a healthy breakfast. Blood samples were obtained before and 1, 2, 4, 6 and 8 h after ingestion. Plasma insulin and IL-6 levels were measured. Intracellular metabolic and inflammatory signalling pathways were assessed by measuring the phosphorylation of Akt kinase and S6K, the degradation of inhibitory κB-α (IκB-α) protein and the DNA binding activity of NF-κB in MNC. mRNA expression levels of the Akt and NF-κB target genes Mn superoxide dismutase (MnSOD), CC-chemokine-receptor 5 (CCR5), intercellular adhesion molecule 1 (ICAM-1) and plasminogen activator inhibitor-1 (PAI-1) were measured by quantitative RT-PCR. We found a positive correlation of Akt phosphorylation with NF-κB activation (NF-κB binding activity: r 0·4500, P= 0·0003; IκB-α protein levels: r − 0·5435, P< 0·0001), a negative correlation of plasma insulin levels with NF-κB binding activity (r − 0·3993, P= 0·0016) and a positive correlation of plasma insulin levels with S6K activation (r 0·4786, P< 0·0001). The activation of Akt and pro-inflammatory NF-κB signalling was supported by the up-regulation of the respective target genes MnSOD and CCR5. In conclusion, the present data suggest a postprandial interaction between the metabolic and inflammatory signalling pathways Akt and NF-κB in MNC.

Bioactive milk proteins may be important in protecting preterm infants from developing inflammation and necrotising enterocolitis (NEC). A preterm pig model was used to investigate the protective effects of enteral bovine lactoferrin (bLF) against NEC development and inflammation. Caesarean-delivered preterm pigs were fed parenteral and minimal enteral nutrition for the first 2 d followed by 2 d of total enteral nutrition before euthanasia. Pigs were stratified into two groups and fed with either a control formula (CON, n 15) or a 10 g/l of bLF-enriched formula (LF, n 13). NEC incidence, gut functions and inflammatory cytokines were analysed. NEC incidence and nutrient absorption were similar between the two groups. In pigs that developed NEC, disease outcome was more severe in the colon accompanied by increased intestinal permeability in LF pigs. In contrary, the LF pigs had a lowered IL-1β level in the proximal small intestine. Dose-dependent effects of bLF on cell proliferation, intracellular signalling and cytokine secretion were tested in porcine intestinal epithelial cells (PsIc1) in vitro. Low doses (0·1–1 g/l) increased cell proliferation via extracellular signal-regulated kinase (ERK), limited IL-8 secretion and prevented NF-κB and hypoxia-inducible factor-1α (HIF-1α) activation, suggesting anti-inflammatory effects. In contrast, at a higher dose (10 g/l), bLF exerted adverse effects by reducing cell proliferation, stimulating IL-8 release, inhibiting ERK activation and up-regulating NF-κB and HIF-1α activation. Overall, at a dose of 10 g/l, bLF exacerbated disease severity in pigs that developed NEC, while the in vitro studies indicated the positive effects of bLF at low doses (0·1–1 g/l). Supplementation of infant formulas with bLF should therefore be optimised carefully.

Chronic inflammatory bowel disease is characterised by an up-regulation of the synthesis and release of a variety of pro-inflammatory mediators leading to excessive tissue injury. Flavonoids are able to inhibit enzymes and/or due to their antioxidant properties regulate the immune response. The goal of the present study was to evaluate the mechanisms of action of phenolic compounds present in grape juice on 2,4,6-trinitrobenzene sulphonic acid (TNBS)-induced colitis. A total of forty-one male Wistar rats were randomised into seven groups: negative control group; TNBS non-treated induced colitis; 2 % grape juice control group; 1 % grape juice 24 h after TNBS colitis induction; 1 % grape juice on day 7 after colitis induction; 2 % grape juice 24 h after colitis induction; 2 % grape juice on day 7 after colitis induction. The 1 % grape juice-treated induced colitis group showed marked clinical improvement when compared with the TNBS-induced colitis group. Rats that received 1 % grape juice, on day 7 after colitis induction, presented reduced intensity of macroscopic and histological scores. Statistically significant differences (P< 0·05) of TNF-α and inducible NO synthase mRNA expression were detected in the groups treated with grape juice at the 1 % dose after inducing experimental colitis when compared with the TNBS group. Grape juice reduced the noxious effects induced by colitis caused by TNBS, especially at the 1 % dose.

Naringenin, one of the most abundant flavonoids in citrus, grapefruits and tomatoes, has been used as a traditional anti-inflammatory agent for centuries. However, the molecular mechanism of naringenin in intestinal inflammation remains unknown so far. The present study investigated a molecular basis for the protective effect of naringenin in dextran sulphate sodium-induced murine colitis. Pre-administration of naringenin significantly reduced the severity of colitis and resulted in down-regulation of pro-inflammatory mediators (inducible NO synthase (iNOS), intercellular adhesion molecule-1 (ICAM-1), monocyte chemoattractant protein-1 (MCP-1), cyclo-oxygenase-2 (Cox2), TNF-α and IL-6 mRNA) in the colon mucosa. The decline in the production of pro-inflammatory cytokines, specifically TNF-α and IL-6, correlated with a decrease in mucosal Toll-like receptor 4 (TLR4) mRNA and protein. Phospho-NF-κB p65 protein was significantly decreased, which correlated with a similar decrease in phospho-IκBα protein. Consistent with the in vivo results, naringenin exposure blocked lipopolysaccharide-stimulated nuclear translocation of NF-κB p65 in mouse macrophage RAW264.7 cells. In addition, in vitro NF-κB reporter assays performed on human colonic HT-29 cells exposed to naringenin demonstrated a significant inhibition of TNF-α-induced NF-κB luciferase expression. Thus, for the first time, the present study indicates that targeted inhibition of the TLR4/NF-κB signalling pathway might be an important mechanism for naringenin in abrogating experimental colitis.

The objective of the present study was to evaluate anti-diabetic effects of chromium picolinate (CrPic) and biotin supplementations in type 2 diabetic rats. The type 2 diabetic rat model was induced by high-fat diet (HFD) and low-dose streptozotocin. The rats were divided into five groups as follows: (1) non-diabetic rats fed a regular diet; (2) diabetic rats fed a HFD; (3) diabetic rats fed a HFD and supplemented with CrPic (80 μg/kg body weight (BW) per d); (4) diabetic rats fed a HFD and supplemented with biotin (300 μg/kg BW per d); (5) diabetic rats fed a HFD and supplemented with both CrPic and biotin. Circulating glucose, cortisol, total cholesterol, TAG, NEFA and malondialdehyde concentrations decreased (P< 0·05), but serum insulin concentrations increased (P< 0·05) in diabetic rats treated with biotin and CrPic, particularly with a combination of the supplements. Feeding a HFD to diabetic rats decreased PPAR-γ expression in adipose tissue and phosphorylated insulin receptor substrate 1 (p-IRS-1) expression of liver, kidney and muscle tissues, while the supplements increased (P< 0·001) PPAR-γ and p-IRS-1 expressions in relevant tissues. Expression of NF-κB in the liver and kidney was greater in diabetic rats fed a HFD, as compared with rats fed a regular diet (P< 0·01). The supplements decreased the expression of NF-κB in diabetic rats (P< 0·05). Results of the present study revealed that supplementing CrPic and biotin alone or in a combination exerts anti-diabetic activities, probably through modulation of PPAR-γ, IRS-1 and NF-κB proteins.

Numerous lines of evidence support a relationship between intestinal inflammation and cancer. Therefore, much attention has recently been focused on the identification of natural compounds with anti-inflammatory activities as a strategy to suppress the early stages of colorectal cancer. Because cocoa is a rich source of bioactive compounds, the present study investigated its anti-inflammatory properties in a rat model of azoxymethane (AOM)-induced colon carcinogenesis and in TNF-α-stimulated Caco-2 cells. A total of forty male rats were fed with control or cocoa-enriched diets (12 %) during 8 weeks and injected with saline or AOM (20 mg/kg body weight) during the third and fourth week (n 10 rats/group). At the end of the experiment, colon samples were evaluated for markers of inflammation. The anti-inflammatory activity of a cocoa polyphenolic extract (10 μg/ml) was examined in TNF-α-stimulated Caco-2 cells, an in vitro model of experimentally induced intestinal inflammation. The signalling pathways involved, including NF-κB and the mitogen-activated protein kinase family such as c-Jun NH2-terminal kinases (JNK), extracellular signal-regulated kinases and p38, were also evaluated. The results show that the cocoa-rich diet decreases the nuclear levels of NF-κB and the expression of pro-inflammatory enzymes such as cyclo-oxygenase-2 and inducible NO synthase induced by AOM in the colon. Additionally, the experiments in Caco-2 cells confirm that cocoa polyphenols effectively down-regulate the levels of inflammatory markers induced by TNF-α by inhibiting NF-κB translocation and JNK phosphorylation. We conclude that cocoa polyphenols suppress inflammation-related colon carcinogenesis and could be promising in the dietary prevention of intestinal inflammation and related cancer development.

Resveratrol, a polyphenol abundantly found in grapes and red wine, exhibits beneficial health effects due to its anti-inflammatory properties. In the present study, we evaluated the effect of resveratrol on inflammatory responses induced by lipopolysaccharide (LPS) treatment of human intestinal Caco-2 and SW480 cell lines. In the LPS-treated intestinal cells, resveratrol dose-dependently inhibited the expression of inducible NO synthase (iNOS) mRNA as well as protein expression, resulting in a decreased production of NO. In addition, Toll-like receptor-4 expression was significantly diminished in LPS-stimulated cells after resveratrol pre-treatment. To investigate the mechanisms by which resveratrol reduces NO production and iNOS expression, we examined the activation of inhibitor of κB (IκB) in LPS-stimulated intestinal cells. Results demonstrated that resveratrol inhibited the phosphorylation, as well as the degradation, of the IκB complex. Overall, these results show that resveratrol is able to reduce LPS-induced inflammatory responses by intestinal cells, interfering with the activation of NF-κB-dependent molecular mechanisms.

The present study was undertaken to evaluate the effect of α-eleostearic acid and punicic acid, two isomers of conjugated linolenic acid (CLnA) present in bitter gourd (Momordica charantia) and snake gourd oil (Trichosanthes anguina), respectively, against oxidative stress, inflammatory challenge and aberration in erythrocyte morphology due to streptozotocin (STZ)-induced diabetes. Male albino rats were divided into four groups consisting of eight animals in each group. The first group served as control and diabetes was induced in rats in groups 2–4 by a single intraperitoneal injection of STZ. Moreover, rats in groups 3 and 4 were treated with 0·5 % of α-eleostearic acid and 0·5 % of punicic acid of the total lipid given, respectively, by oral administration once per d. After administration, CLnA isomers had significantly reduced oxidative stress, lipid peroxidation and restored antioxidant and pro-inflammatory enzymes such as superoxide dismutase, catalase, and glutathione peroxidase, reduced glutathione, NO synthase level in pancreas, blood and erythrocyte lysate. The ferric reducing antioxidant power (FRAP) assay of plasma showed that CLnA treatment caused improvement in the FRAP value which was altered after STZ treatment due to an increased level of free radicals. Expression of inflammatory cytokines such as TNF-α and IL-6 in blood and expression of hepatic NF-κB (p65) increased significantly after STZ treatment due to increased inflammation which was restored with the administration of CLnA isomers. From the obtained results, it could be concluded that α-eleostearic acid and punicic acid showed potent antioxidant and anti-inflammatory activity with varying effectivity.

Moderate alcohol consumption has various effects on immune and inflammatory processes, which could accumulatively modulate chronic disease risk. So far, no comprehensive, integrative profiling has been performed to investigate the effects of longer-term alcohol consumption. Therefore, we studied the effects of alcohol consumption on gene expression patterns using large-scale profiling of whole-genome transcriptomics in blood cells and on a number of proteins in blood. In a randomised, open-label, cross-over trial, twenty-four young, normal-weight men consumed 100 ml vodka (30 g alcohol) with 200 ml orange juice or only orange juice daily during dinner for 4 weeks. After each period, blood was sampled for measuring gene expression and selected proteins. Pathway analysis of 345 down-regulated and 455 up-regulated genes revealed effects of alcohol consumption on various signalling responses, immune processes and lipid metabolism. Among the signalling processes, the most prominently changed was glucocorticoid receptor signalling. A network on immune response showed a down-regulated NF-κB gene expression together with increased plasma adiponectin and decreased pro-inflammatory IL-1 receptor antagonist and IL-18, and acute-phase proteins ferritin and α1-antitrypsin concentrations (all P < 0·05) after alcohol consumption. Furthermore, a network of gene expression changes related to lipid metabolism was observed, with a central role for PPARα which was supported by increased HDL-cholesterol and several apo concentrations (all P < 0·05) after alcohol consumption. In conclusion, an integrated approach of profiling both genes and proteins in blood showed that 4 weeks of moderate alcohol consumption altered immune responses and lipid metabolism.

Diets rich in SFA have been implicated in Alzheimer's disease (AD). There is strong evidence to suggest that microglial activation augments the progression of AD. However, it remains uncertain whether SFA can initiate microglial activation and whether this response can cause neuronal death. Using the BV-2 microglial cell line and primary microglial culture, we showed that palmitic acid (PA) and stearic acid (SA) could activate microglia, as assessed by reactive morphological changes and significantly increased secretion of pro-inflammatory cytokines, NO and reactive oxygen species, which trigger primary neuronal death. In addition, the mRNA level of these pro-inflammatory mediators determined by RT-PCR was also increased by PA and SA. We further investigated the intracellular signalling mechanism underlying the release of pro-inflammatory mediators from PA-activated microglial cells. The present results showed that PA activated the phosphorylation and nuclear translocation of the p65 subunit of NF-κB. Furthermore, pyrrolidine dithiocarbamate, a NF-κB inhibitor, attenuated the production of pro-inflammatory mediators except for IL-6 in PA-stimulated microglia. Administration of anti-Toll-like receptor (TLR)4-neutralising antibody repressed PA-induced NF-κB activation and pro-inflammatory mediator production. In conclusion, the present in vitro study demonstrates that SFA could activate microglia and stimulate the TLR4/NF-κB pathway to trigger the production of pro-inflammatory mediators, which may contribute to neuronal death.

Plant polyphenols, i.e. green tea extract (GTE), possess high antioxidative and anti-inflammatory capacity, thus being protective in various models of acute inflammation. However, their anti-inflammatory effect and a feasible mechanism in haemorrhage/resuscitation (H/R)-induced liver injury remain unknown. We investigated the effects of GTE and the role of NF-κB in the pathogenesis of liver injury induced by H/R, and their effects on intercellular adhesion molecule-1 (ICAM-1) expression and neutrophil infiltration. Female Lewis rats were fed a standard chow diet (control, ctrl) or a diet containing 0·1 % polyphenolic GTE for five consecutive days before H/R. Rats were haemorrhaged to a mean arterial pressure of 30 (sem 2) mmHg for 60 min and resuscitated. Control groups (sham_ctrl and sham_GTE) underwent surgical procedures without H/R. At 2 h after resuscitation, tissues were harvested. Serum alanine aminotransferase (ALT) and IL-6 were measured. Hepatic necrosis, ICAM-1 expression and polymorphonuclear leucocyte (PMNL) infiltration were assessed. Hepatic expression of IκBα (phospho) was measured. H/R induced strong liver damage with increased necrosis and serum ALT levels. Compared with both sham groups, inflammatory markers (serum IL-6 and hepatic PMNL infiltration) were elevated after H/R (P < 0·05). Also, H/R increased IκBα phosphorylation. GTE administration markedly (P < 0·05) decreased serum ALT and IL-6 levels, hepatic necrosis as well as PMNL infiltration and the expression of ICAM-1 and phosphorylated IκBα compared with H/R. In conclusion, we observed that NF-κB activation plays an important role in the pathogenesis of liver injury after H/R through the up-regulation of hepatic ICAM-1 expression and subsequent PMNL infiltration. GTE pre-treatment prevents liver damage in this model of acute inflammation through a NF-κB-dependent mechanism.

The activation of PPARγ by ligands, including conjugated linoleic acid (CLA) isomers, plays an important role in the immune response. Among CLA isomers, trans-10, cis-12 (t10c12)-CLA is known to participate in the modulation of pro-inflammatory cytokine secretion. The aim of the present study was to assess the effect of t10c12-CLA on PPARγ activation, NF-κB activation and TNF-α expression in lipopolysaccharide (LPS)-naive and LPS-stimulated porcine peripheral blood mononuclear cells (PBMC). In addition, the effect of PPARγ inhibition on NF-κB activation and TNF-α expression in porcine PBMC was examined. t10c12-CLA was found to increase TNF-α expression and NF-κB activity in LPS-naive porcine PBMC. In contrast, t10c12-CLA decreased TNF-α expression and NF-κB activity in LPS-stimulated porcine PBMC. t10c12-CLA up-regulated PPARγ activity and mRNA expression in both LPS-naive and LPS-stimulated porcine PBMC. GW9662, a PPARγ antagonist, completely negated the modulating effects of t10c12-CLA on TNF-α expression and NF-κB activity in both LPS-naive and LPS-stimulated porcine PBMC. These results suggest that t10c12-CLA can modulate TNF-α production and NF-κB activation by a PPARγ-dependent pathway in porcine PBMC.

Polyphenols exert beneficial effects in atherosclerosis. The crucial step in atherosclerosis is the recruitment of monocytes to the subendothelial space, induced by endothelial adhesion molecules through the activation of factors such as NF-κB. We studied the effect of a dealcoholised lager beer (DLB) and a dealcoholised dark beer (DDB) on atherosclerotic lesions, and the underlying mechanisms. Dealcoholised beers were administered in the diet (42 ml/kg body weight per d) to 4-week-old male apoE knockout (apoE − / − ) mice for 20 weeks. The atherosclerotic lesions in the thoracic aorta were reduced by 44 % (P = 0·003) and 51 % (P < 0·001) in DLB- and DDB-treated mice, respectively. Also, the mRNA expressions of the endothelial adhesion molecules in the total aorta were decreased: P-selectin showed a 17 % (P = 0·004) reduction in DDB-treated mice; vascular cell adhesion molecule-1 (VCAM-1) was decreased by 20 % (P = 0·012) and 32 % (P = 0·001) in DLB- and DDB-treated mice, respectively; intercellular adhesion molecule-1 (ICAM-1) showed a 14 % (P = 0·014) reduction in DLB-treated mice. The protein expressions of these molecules and NF-κB were studied in the aortic root. P-selectin was decreased by 37 % (P = 0·012) in DDB-treated mice; VCAM-1 was reduced by 48 % (P = 0·001) and 54 % (P < 0·001) in DLB- and DDB-treated mice, respectively; ICAM-1 was decreased by 25 % (P = 0·028) and 30 % (P = 0·018) in DLB- and DDB-treated mice, respectively; NF-κB was reduced by 46 % (P = 0·042) in DDB-treated mice. In conclusion, dealcoholised beers protected apoE − / −  mice against atherosclerosis, through the modulation of endothelial adhesion molecules, possibly induced by NF-κB.

The anti-inflammatory effects of two esters of α-tocopherol (α-TOH), all-rac-α-TOH acetate (dl-α-TOA) and RRR-α-TOH succinate (d-α-TOS), on broilers repeatedly challenged with lipopolysaccharide (LPS) were investigated. Three hundred and twenty 1-d-old broiler chicks were allotted into four treatment groups and fed on a control diet (30 mg/kg dl-α-TOA) or diets containing 10, 30, 50 mg/kg d-α-TOS. Half of the birds from each treatment group were challenged with 0·9 % NaCl solution or LPS (250 μg/kg body weight) at 16, 18 and 20 d of age. The results indicated that the pretreatment of birds with 50 mg/kg d-α-TOS markedly reduced serum PGE2 secretion and increased the concentrations of serum or hepatic α-TOH. When LPS-challenged birds were pretreated with 30 or 50 mg/kg d-α-TOS, the increases of plasma and splenic concentrations of interferon-γ, IL-1β, IL-2, IL-6, IL-4 and IL-10 were dramatically attenuated. Also, a significant decrease of hepatic reactive oxygen species (ROS) and hepatic or splenic phosphokinase C (PKC) activities was found in birds pretreated with 30 or 50 mg/kg d-α-TOS. Furthermore, d-α-TOS inhibited the activation of NF-κB by preventing the degradation of inhibitory-κBα. In conclusion, D-α-TOS is able to prevent LPS-induced inflammation response in vivo. The beneficial effect may depend on suppressing the secretion of various plasma and splenic inflammatory mediators through inhibiting NF-κB activation and by blocking ROS signalling, in which PKC may play an assistant role.