Nuclear factor-kappaB Transcription Research Articles

Trichodimerol inhibits inflammation through suppression of the nuclear transcription factor-kappaB/NOD-like receptor thermal protein domain associated protein 3 signaling pathway.

Excessive inflammation causes chronic diseases and tissue damage. Although there has been drug treatment, its side effects are relatively large. Searching for effective anti-inflammatory drugs from natural products has become the focus of attention. First isolated from Trichoderma longibraciatum, trichodimerol is a natural product with TNF inhibition. In this study, lipopolysaccharide (LPS)-induced RAW264.7 macrophages were used as a model to investigate the anti-inflammatory activity of trichodimerol. The results of nitric oxide (NO) detection, enzyme-linked immunosorbent assay (ELISA), and reactive oxygen species (ROS) showed that trichodimerol could reduce the production of NO, ROS, and the proinflammatory cytokines interleukin (IL)-6 and tumor necrosis factor (TNF)-α. Western blotting results showed that trichodimerol could inhibit the production of inflammatory mediators such as cyclooxygenase (COX)-2 and inducible nitric oxide synthase (iNOS) and the protein expression of nuclear transcription factor-kappaB (NF-κB), p-IKK, p-IκB, Toll-like receptor 4 (TLR4), NOD-like receptor thermal protein domain associated protein 3 (NLRP3), cysteinyl aspartate specific proteinase (Caspase)-1, and ASC, which indicated that trichodimerol may inhibit inflammation through the NF-κB and NLRP3 pathways. At the same time, molecular docking showed that trichodimerol can directly combine with the TLR4-MD2 complex. Hence, trichodimerol inhibits inflammation by obstructing the interaction between LPS and the TLR4-MD2 heterodimer and suppressing the downstream NF-κB and NLRP3 pathways.

Advanced wound healing with application of products with diversified propolis

In the understanding that we have in our country the industry and the raw material of elaboration of products derived from propolis, based on the evidence published in scientific articles that refer to the anti-inflammatory activity of propolis which is linked to the ability of its constituent polyphenols (flavonoids and aromatic acids) to inhibit NF-kB (nuclear transcription factor kappa-b) and reducing the levels of inflammatory mediators, this produces a decrease in inflammation, pain and microbial load, it is then that for this reason it was decided to clinically verify the efficacy of this product in complex wounds by conducting a descriptive, prospective cross-sectional study.

Dual roles of ANGPTL4 in multiple inflammatory responses in stomatitis mice.

Stomatitis is inflammation of the oral mucosa. Angiopoietin-like protein 4 (ANGPTL4) has pleiotropic functions both anti-inflammatory and pro-inflammatory properties. In the present study, we tested whether there is a correlation between increased ANGPTL4 expression and inflammation in stomatitis mice and the mechanisms involved. In this study, the oral mucosa of mice was burned with 90% phenol and intraperitoneal injection of 5-fluorouracil to establish the model of stomatitis mice. The pathological changes of stomatitis mice were observed by H&E staining of paraffin section. The expressions of cytokines and ANGPTL4 were detected by fluorescence quantitative PCR, and the protein levels of ANGPTL4 were detected by western blot. Compared with control group, the oral mucosal structure of model mice was damaged. The expression of ANGPTL4 were significantly increased concomitantly with elevated production of anti-inflammatory cytokine (peroxisome proliferator-activated receptoralpha) and pro-inflammatory cytokines [nuclear transcription factor-kappaB, interleukin-6 (IL-6), IL-1β, and tumor necrosis factor-α] in mice with stomatitis. This study suggests that ANGPTL4 may be a double-edged sword in multiple inflammatory responses in stomatitis mice.

Muscone Can Improve Spinal Cord Injury by Activating the Angiogenin/Plexin-B2 Axis.

Spinal cord injury (SCI) is a devastating neurological disorder that usually damages sensorimotor and autonomic functions. Signaling pathways can play a key role in the repair process of SCI. The plexin-B2 acts as a receptor for angiogenin and mediates ribosomal RNA transcription, influencing cell survival and proliferation. Protein kinase B serine/threonine kinase interacts with angiogenin to form a positive feedback effect. Brain-derived neurotrophic factor (BDNF) and vascular endothelial growth factor can induce angiogenin nuclear translocation. Moreover, the BDNF can promote the secretion of angiogenin. Interestingly, all of them can activate the angiogenin/plexin-B2 axis. Muscone has anti-inflammatory and proliferative features as it can inhibit nuclear transcription factor kappa-B (NF-κB) and activate the angiogenin/plexin-B2 axis, thus being significant agent in the SCI repair process. Herein, we review the potential mechanism of angiogenin/plexin-B2 axis activation and the role of muscone in SCI treatment. Muscone may attenuate inflammatory responses and promote neuronal regeneration after SCI.

Sulforaphane alleviates LPS-induced inflammatory injury in ARPE-19 cells by repressing the PWRN2/NF-kB pathway

Background Age-related macular degeneration (AMD) is the leading cause of blindness in the elderly population and its pathogenesis has been associated with inflammatory damage to retinal pigment epithelial (RPE) cells. Here, we explored the ability of sulforaphane to protect ARPE-19 cells from lipopolysaccharide (LPS)-induced inflammatory injury and elucidated the underlying molecular mechanism. Methods Cell viability, apoptosis, inflammation, PWRN2 expression, nuclear transcription factor-kappa B (NF-kB) activity, and the interaction between PWRN2 and the IkBa protein were assessed in RPE cells under- or over-expressing PWRN2 that had been treated with LPS and sulforaphane. Results Overexpression of PWRN2 in LPS-treated cells promoted NF-kB activation by interacting with IkBa, thus reducing cell viability. In contrast, PWRN2 downregulation repressed LPS-induced NF-kB activation and apoptosis in RPE cells. Similarly, sulforaphane downregulated PWRN2 and inhibited NF-kB activation in a concentration-dependent manner. Conversely, PWRN2 overexpression or NF-kB upregulation weakened the anti-inflammatory effects of sulforaphane. Conclusion Our results suggest that sulforaphane protects RPE cells from LPS-induced inflammatory injury by suppressing the PWRN2/NF-kB pathway.

Polygonum cuspidatum glycoside mitigated LPS-induced human endometrial stromal cell inflammation by regulating NF-κB/Nrf2 signaling pathway-related proteins

Purpose: To study the influence of polydatin on LPS-provoked human endometrial stromal cell inflammation, and its mechanism of action.Methods: Fifty ICR female mice were selected and assigned to control and three-dose polydatin groups. Before establishment of the model, mice in low-dose group, middle-dose group and high-dose group were given polydatin at doses of 5, 10 and 20 mg/kg, respectively, by oral gavage for 5 days. Protein expression levels of interleukin 1β (IL-1 β), tumor necrosis factor- α (TNF-α) level, nuclear factor E2-related factor 2 (NRF-2) and nuclear transcription factor kappa-B (NF-2 κB) were determined with Western blot assay.Results: Model group mice protein levels of NF- κB and nrf-2 were significantly reduced, relative to the corresponding control values (p < 0.05). The NF-κB and NRF-2 proteins in model group were markedly up-regulated, relative to control group, but they were and dose-dependently lower in the 3 polydatin groups than in control (p < 0.05). Conclusion: Polydatin reduces LPS-induced inflammatory response in mouse endometrial stromal cells, and promotes the repair of endometrium and regeneration of glands via a mechanism related to regulation of NF-κ B/Nrf2 signaling pathway-related proteins.

Acute and Subacute Safety Evaluation of Black Tea Extract (Herbt Tea Essences) in Mice.

Theabrownin (TB) is a heterogeneous biomacromolecule, extracted from tea, with many functional groups. Importantly, TB possesses diverse health benefits, such as antitumor activity and blood lipid-lowering effects. Presently, the content of TB in tea extract is relatively low. Here, we obtained a deep-processed black tea extract with a high content of TB (close to 80%), which was named Herbt Tea Essences (HTE). Currently, this study was designed to evaluate the biosafety of high-content TB products on mice. We implemented acute and subacute toxic experiments to assess its safety on organs, the serum biochemical and molecular levels. In the acute exposure study, we found that the median lethal dose (LD50) value of HTE was 21.68 g/kg (21.06–24.70 g/kg, greater than 5 g/kg), suggesting that HTE had a low acute toxicity. In the 28-day subacute exposure study, our results showed that no abnormal effects were observed in the 40 and 400 mg/kg/day HTE-treated groups. However, we observed slight nephrotoxicity in the 4000 mg/kg/day HTE-treated group. The HTE-induced nephrotoxic effect might involve the inflammatory response activation mediated by the nuclear transcription factor kappa-B (NF-κB) signaling pathway. This study would provide valuable data for the TB safety assessment and promote this natural biomacromolecule application in daily drinking.

Anti-Inflammatory Mechanism of An Alkaloid Rutaecarpine in LTA-Stimulated RAW 264.7 Cells: Pivotal Role on NF-κB and ERK/p38 Signaling Molecules.

Lipoteichoic acid (LTA) is a key cell wall component and virulence factor of Gram-positive bacteria. LTA contributes a major role in infection and it mediates inflammatory responses in the host. Rutaecarpine, an indolopyridoquinazolinone alkaloid isolated from Evodia rutaecarpa, has shown a variety of fascinating biological properties such as anti-thrombotic, anticancer, anti-obesity and thermoregulatory, vasorelaxing activity. It has also potent effects on the cardiovascular and endocrine systems. Herein, we investigated rutaecarpine’s (Rut) anti-inflammatory effects in LTA-stimulated RAW macrophage cells. The Western blot and spectrophotometric results revealed that Rut inhibited the production of nitric oxide (NO) and the expression of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and interleukin (IL)-1β in the LTA-induced macrophage cells. Successively, our mechanistic studies publicized that Rut inhibited LTA-induced phosphorylation of mitogen-activated protein kinase (MAPK) including the extracellular signal-regulated kinase (ERK), and p38, but not c-Jun NH2-terminal kinase (JNK). In addition, the respective Western blot and confocal image analyses exhibited that Rut reserved nuclear transcription factor kappa-B (NF-κB) by hindering inhibitor of nuclear factor κB-α (IκBα) and NF-κB p65 phosphorylation and p65 nuclear translocation. These results indicate that Rut exhibits its anti-inflammatory effects mainly through attenuating NF-κB and ERK/p38 signaling pathways. Overall, this result suggests that Rut could be a potential therapeutic agent for the treatment of Gram-positive bacteria induced inflammatory diseases.

The Role of Selenoprotein Tissue Homeostasis in MetS Programming: Energy Balance and Cardiometabolic Implications.

Selenium (Se) is an essential trace element mainly known for its antioxidant, anti-inflammatory, and anti-apoptotic properties, as it is part of the catalytic center of 25 different selenoproteins. Some of them are related to insulin resistance (IR) and metabolic syndrome (MetS) generation, modulating reactive oxygen species (ROS), and the energetic sensor AMP-activated protein kinase (AMPK); they can also regulate the nuclear transcription factor kappa-B (NF-kB), leading to changes in inflammation production. Selenoproteins are also necessary for the correct synthesis of insulin and thyroid hormones. They are also involved in endocrine central regulation of appetite and energy homeostasis, affecting growth and development. MetS, a complex metabolic disorder, can appear during gestation and lactation in mothers, leading to energetic and metabolic changes in their offspring that, according to the metabolic programming theory, will produce cardiovascular and metabolic diseases later in life. However, there is a gap concerning Se tissue levels and selenoproteins’ implications in MetS generation, which is even greater during MetS programming. This narrative review also provides an overview of the existing evidence, based on experimental research from our laboratory, which strengthens the fact that maternal MetS leads to changes in Se tissue deposits and antioxidant selenoproteins’ expression in their offspring. These changes contribute to alterations in tissues’ oxidative damage, inflammation, energy balance, and tissue function, mainly in the heart. Se imbalance also could modulate appetite and endocrine energy balance, affecting pups’ growth and development. MetS pups present a profile similar to that of diabetes type 1, which also appeared when dams were exposed to low-Se dietary supply. Maternal Se supplementation should be taken into account if, during gestation and/or lactation periods, there are suspicions of endocrine energy imbalance in the offspring, such as MetS. It could be an interesting therapy to induce heart reprogramming. However, more studies are necessary.

Ендотелій та системне запалення: роль ядерних транскрипційних факторів і терапевтичні можливості (огляд літератури)

Ендотелій відіграє винятково важливу роль у фізіології та патології людини. Ендотеліальна дисфункція: формування прозапального та протромботичного фенотипу ендотеліальних клітин, надлишкова продукція цитокинів запалення, зниження продукції вазодилататорів і збільшення вазоконстрикторів та протромботичних медіаторів — основа патогенезу системного запалення (СЗ) та асоційованих із ним хвороб: артеріальної гіпертонії, атеросклерозу, ішемічної хвороби серця, ожиріння, цукрового діабету 2-го типу. Ядерний транскрипційний фактор каппа В (NFkB) є головним індуктором СЗ в ендотеліальних клітинах, а рецептори, що активуються проліфераторами пероксисом (PPAR-α, -β/-δ і -γ), — антагоністи NFkB — регуляторами інтенсивності СЗ. Вивчення молекулярних механізмів дії NFkB і PPAR дозволяє використовувати антагоніст NFkB — метформін і агоніст PPAR-γ — піоглітазон у лікуванні захворювань, пов’язаних із СЗ, а також сподіватися на створення нових препаратів.

Targeting MAPK/NF-κB Pathways in Anti-Inflammatory Potential of Rutaecarpine: Impact on Src/FAK-Mediated Macrophage Migration.

Studies have discovered that different extracts of Evodia rutaecarpa and its phytochemicals show a variety of biological activities associated with inflammation. Although rutaecarpine, an alkaloid isolated from the unripe fruit of E. rutaecarpa, has been exposed to have anti-inflammatory properties, the mechanism of action has not been well studied. Thus, this study investigated the molecular mechanisms of rutaecarpine (RUT) in lipopolysaccharide (LPS)-induced RAW 264.7 macrophages. RUT reserved the production of nitric oxide (NO) and the expression of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), tumor necrosis factor (TNF-α), and interleukin (IL)-1β in the LPS-induced macrophages. RUT showed an inhibitory effect on the mitogen-activated protein kinases (MAPKs), and it also inhibited nuclear transcription factor kappa-B (NF-κB) by hindering IκBα and NF-κB p65 phosphorylation and p65 nuclear translocation. The phospho-PI3K and Akt was concentration-dependently suppressed by RUT. However, RUT not only suggestively reduced the migratory ability of macrophages and their numbers induced by LPS but also inhibited the phospho-Src, and FAK. Taken together, these results indicate that RUT participates a vital role in the inhibition of LPS-induced inflammatory processes in RAW 264.7 macrophages and that the mechanisms involve PI3K/Akt and MAPK-mediated downregulation of NF-κB signaling pathways. Notably, reducing the migration and number of cells induced by LPS via inhibiting of Src/FAK pathway was also included to the anti-inflammatory mechanism of RUT. Therefore, RUT may have potential benefits as a therapeutic agent against chronic inflammatory diseases.

TREM-1 amplifies trophoblastic inflammation via activating NF-κB pathway during preeclampsia.

Excessive activation of maternal systemic inflammation is one of the underlying causes of pathology during the disease course of preeclampsia (PE). The triggering receptor expressed on myeloid cells-1 (TREM-1) participates in the development and persistence of inflammation. We hypothesized that dysregulated TREM-1 may be involved in the pathogenesis of PE by promoting the secretion of trophoblastic pro-inflammatory cytokines that augment inflammation. The localization of TREM-1 in placenta and the extravillous trophoblast cell line (TEV-1) was determined by immunohistochemical staining. The expression level of TREM-1 and pro-inflammatory cytokines in placentas were compared between normal pregnancies and PE. We used lipopolysaccharide (LPS) to simulate trophoblastic inflammation. TEV-1cells were transfected with TREM-1 plasmid and si-TREM-1 respectively, and then were incubated with LPS. The expression levels of pro-inflammatory cytokines and key molecules featured in nuclear transcription factor-kappaB (NF-κB) pathway were detected. Transwell assays were used to detect the effects of TREM-1 on cell migration and invasion. TREM-1 was localized on both villous trophoblasts (VTs) and extravillous trophoblasts (EVTs). TREM-1 and pro-inflammatory cytokines were up-regulated in preeclamptic placenta. Overexpression of TREM-1 promoted the activation of NF-κB pathway and the release of pro-inflammatory factors induced by LPS, and enhanced migration and invasion of TEV-1cells. Inhibition of TREM-1 significantly attenuated LPS-induced effects and suppressed migration and invasion. This study suggested that TREM-1 was up-regulated in PE, and may promote the production of downstream inflammatory factors by activating NF-κB pathway in trophoblastic cells, thus exerting pro-inflammatory effects in the pathogenesis of PE.

Therapeutic Potential for Regulation of the Nuclear Factor Kappa-B Transcription Factor p65 to Prevent Cellular Senescence and Activation of Pro-Inflammatory in Mesenchymal Stem Cells.

Mesenchymal stem cells have an important potential in the treatment of age-related diseases. In the last years, small extracellular vesicles derived from these stem cells have been proposed as cell-free therapies. Cellular senescence and proinflammatory activation are involved in the loss of therapeutic capacity and in the phenomenon called inflamm-aging. The regulators of these two biological processes in mesenchymal stem cells are not well-known. In this study, we found that p65 is activated during cellular senescence and inflammatory activation in human umbilical cord-derived mesenchymal stem cell. To demonstrate the central role of p65 in these two processes, we used small-molecular inhibitors of p65, such as JSH-23, MG-132 and curcumin. We found that the inhibition of p65 prevents the cellular senescence phenotype in human umbilical cord-derived mesenchymal stem cells. Besides, p65 inhibition produced the inactivation of proinflammatory molecules as components of a senescence-associated secretory phenotype (SASP) (interleukin-6 and interleukin-8 (IL-6 and IL-8)). Additionally, we found that the inhibition of p65 prevents the transmission of paracrine senescence between mesenchymal stem cells and the proinflammatory message through small extracellular vesicles. Our work highlights the important role of p65 and its inhibition to restore the loss of functionality of small extracellular vesicles from senescent mesenchymal stem cells and their inflamm-aging signature.

A novel gastroprotective effect of zeaxanthin against stress-induced gastritis in male rats targeting the expression of HIF-1α, TFF-1 and MMP-9 through PI3K/Akt/JNK signaling pathway

Stress-induced gastritis is a common problem in the intensive care unit. Zeaxanthin (ZE), a non-provitamin A carotenoid has been known to exert antioxidant and anti-inflammatory effects. In this study, we examined the effect of ZE on water avoidance stress (WAS)-induced gastritis in rats. 24 Sprague' Dawley male rats were divided into four groups; control, ZE, WAS and WAS+ZE. In the stressed rats, treatment with ZE effectively downregulated the gastric levels of total oxidant status (TOS), myeloperoxidase (MPO) and malondialdehyde (MDA), with significant upregulation of the antioxidant enzymes' activities and gastric levels of prostagladin-E2 (PGE2) as compared to the untreated stressed one. As noticed in the present study, ZE significantly decrease the gastric levels of interleukin-1 β (IL-1β) and IL-6 as well as suppression of nuclear transcription factor kappa-B (NF-κB) immunohistochemical expression together with upregulation of trefoil factor-1 (TFF-1) gene expression. Moreover, in the untreated WAS-induced gastritis group, gastrin and corticosterone levels were significantly increased together with upregulation of the gene expression of hypoxia inducible factor-1α (HIF-1α), matrix metalloproteinase-9 (MMP-9), PI3K, Akt and JNK in the gastric tissues, which significantly improved by ZE administration. These all positive effects of ZE reflected on reduction of microscopic gastric mucosal damage and inflammatory cell infiltration with improvement of ulcer score. Our results discover that ZE has a new gastroprotective effect against stress-induced gastritis in rats, primarily through its antioxidative and anti-inflammatory effects, which are expressed in the regulation of the MMP-9 and HIF-1α signaling pathways.

Pinocembrin Reduces Arthritic Symptoms in Mouse Model via Targeting Sox4 Signaling Molecules.

Rheumatoid arthritis (RA) is a chronic autoimmune, multifactorial, inflammatory disorder characterized by hyperplasia and infiltration of inflammatory cells at the synovial lining leading to destruction of cartilage and bone tissues. Pinocembrin (PCB) is a natural flavonoid extracted as a pure molecule from honey, propolis, and some plants. In this study, we evaluated the antiarthritic effect of PCB in adjuvant induced arthritis (AIA) mice. Treating the AIA mouse model with PCB reduced the arthritis symptoms/score, including edema size, extent of hind paw redness, abnormal movement, and holding inability. At the pathological level, PCB significantly decreased the joint erosion and percentages of infiltrated inflammatory cells. Biochemically, PCB interacts with the transcription factor, SRY-related HMG-box 4 (Sox4), and then modulates its dysregulated expression and the expression of Sox4/Stat3 signaling molecules in AIA mice. These molecules include tumor necrosis factor-α, nuclear transcription factor kappaB, and cyclooxygenase-2, besides the microRNAs; miR-132, miR-202-5p, and miR-7235, which are dysregulated in adjuvant-induced arthritis model relative to the control mice. The possible PCB interaction with Sox4 transcriptional protein was confirmed through molecular docking where three hydrogen bonds were formed at ARG and LYS residues at a stable binding energy of -4.72. Taken together, our data demonstrate that PCB could serve as a therapeutic drug in treatment of RA.

Protective role of Oleuropein, an olive tree secoiridoid and its acyl-derivate in experimental models of rheumatic diseases

Oleuropein (OL), an olive tree secoiridoid, and its peracetylated derivate (Per-OL) have exhibited several beneficial effects reducing acute inflammatory responses on LPS-stimulated macrophages. The present study was designed to evaluate the effects of both dietary OL and Per-OL supplementations on collagen-induced arthritis (CIA) murine model. Three-weeks-old DBA-1/J male mice were fed from weaning with 0.05% (w/w) OL, 0.05% or 0.025% Per-OL. After six weeks of pre-treatment, arthritis was induced by bovine collagen type II by tail base injection (day 0) and mice received a booster injection on day 21. Mice were sacrificed 42 days after first immunization. Then, blood was recollected and paws were histological and biochemically processed. OL and Per-OL experimental diets significantly prevented histological damage and arthritic score development in RA. In addition, serum collagen oligomeric matrix protein (COMP) and metalloproteinase 3 (MMP)-3 as well as proinflammatory cytokines levels in paw homogenates (including tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, IL-17 and interferon (IFN)-γ were significantly ameliorated in those animals fed with dietary secoiridoids. Mitogen-activated protein kinases (MAPKs) and nuclear transcription factor kappa-B (NF-κB) activations were drastically down-regulated whereas nuclear factor E2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) protein expressions were significantly up-regulated in those mice fed with OL and Per-OL diets. These results reveal, for the first time, the anti-inflammatory effect of a diet supplemented with OL and Per-OL in an experimental murine model of CIA, which was accompanied by a significant reduction in the pro-inflammatory markers studied (COMP, MMP-3, TNF-α, IL-1β, IL-6, IL-17 and IFN-γ). The mechanisms involved could be related to an activation of the antioxidant pathway Nrf2/HO-1 and an inhibition of MAP kinases and NF-κB signaling pathways activations. On the other hand, we studied the effects of both OL and Per-OL diets supplemented diets in a model of pristane-induced systemic lupus erythematosus (SLE) in BALB / c mice. Mice received an intraperitoneal injection of pristane or saline according to the experimental groups and were fed with experimental diets enriched with OL and Per-OL. Changes in cytokines levels and pro-inflammatory markers were evaluated by the ELISA assay. Changes in the protein expression of inducible nitric oxide synthase (iNOS), microsomal prostaglandin E synthase 1 (mPGEs-1) as well as HO-1, nuclear factor Nrf2, p38 protein kinases, C-jun NH2-terminal kinase (JNK) and extracellular signal-regulated kinase (ERK), signal transduction factor and activator of transcription (STAT) -3, NF-κB and inflammasome NLRP3 activation were determined using the Western Blot. Both OL and Per-OL dietary treatments significantly reduced kidney damage and reduced serum MMP-3 and renal prostaglandin E2 (PGE2) levels. Our studies indicated that OL and Per-OL enriched diets produced an increase in the expression of the antioxidant pathway Nrf2 / HO-1 which was accompanied by a decrease in the activation of the Janus kinases and signal transducer and activator of transcription (JAK / STAT), MAPKs, NF-κB and inflammasome NLRP3 proteins. In conclusion, dietary supplementation with OL and Per-OL could serve as the basis for the development of new nutritional strategies for the prevention of RA. In addition, these results also suggest that dietary supplementation with OL and Per-OL could constitute a new alternative therapeutic approach as a preventive or palliative of nephritis in the management of SLE.

Effects of Artemisia argyi flavonoids on growth performance and immune function in broilers challenged with lipopolysaccharide.

ObjectiveThis research aimed to study the effects of Artemisia argyi flavonoids (AAF) supplemented in diets on the growth performance and immune function of broiler chickens challenged with lipopolysaccharide (LPS).MethodsA total of one hundred and ninety-two 1-d-old broiler chicks were assigned into 4 treatment groups, which were, respectively, fed a basal diet (control), fed a diet with 750 mg/kg AAF, fed a basal diet, and challenged with LPS, fed a diet with 750 mg/kg AAF, and challenged with LPS. Each treatment had six pens with 8 chicks per pen. On days 14, 16, 18, 20 (stress phase I) and 28, 30, 32, 34 (stress phase II), broilers were injected with LPS (500 μg/kg body weight) or an equivalent amount of saline.ResultsThe results demonstrated that dietary AAF significantly improved the body weight (d 21) and alleviated the decrease of average daily gain in broilers challenged with LPS on d 21 and d 35 (p<0.05). Dietary AAF increased bursa fabricius index, and dramatically attenuated the elevation of spleen index caused by LPS on d 35 (p<0.05). Furthermore, serum interleukin-6 (IL-6) concentration decreased with AAF supplementation on d 21 (p<0.05). Diet treatment and LPS challenge exhibited a significant interaction for the concentration of IL-1β (d 21) and IL-6 (d 35) in serum (p<0.05). Additionally, AAF supplementation mitigated the increase of IL-1β, IL-6 in liver and spleen induced by LPS on d 21 and 35 (p<0.05). This study also showed that AAF supplementation significantly reduced the expression of IL-1β (d 21) and nuclear transcription factor kappa-B p65 (d 21 and 35) in liver (p<0.05), and dietary AAF and LPS treatment exhibited significant interaction for the gene expression of IL-6 (d 21), toll like receptor 4 (d 35) and myeloid differentiation factor 88 (d 35) in spleen (p<0.05).ConclusionIn conclusion, AAF could be used as a potential natural immunomodulator to improve growth performance and alleviate immune stress in broilers challenged with LPS.

Fish oil attenuated dystrophic muscle markers of inflammation via FFA1 and FFA4 in the mdx mouse model of DMD.

In the present study we investigated the involvement of free fatty acid (FFA) receptors in the anti-inflammatory role of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in dystrophic muscles, by administering FFA blockers in the mdx mouse model of dystrophy. Mdx mice (3months-old) were treated with fish oil capsules (FDC Vitamins; 0.4g EPA and 0.2g DHA; gavage) alone or concomitant to FFA1 and FFA4 blockers (GW1100 and AH7614; i.p.). C57BL/10 mice (3months-old) and untreated-mdx mice received mineral oil and were used as controls. After 1month of treatment, plasma markers of myonecrosis (total and cardiac creatine kinase; CK), the levels of FFA1 and FFA4 and of the markers of inflammation, nuclear transcription factor kappa B (NFkB), tumor necrosis factor alpha (TNF-α) and interleukin 1β (IL-1β) were analyzed in the diaphragm muscle and heart by western blot. Fish oil significantly reduced total CK, cardiac CK and the levels of NFkB (diaphragm), and of TNF-α and IL-1β (diaphragm and heart) in mdx. In the dystrophic diaphragm, FFA1 was increased compared to normal. Blockers of FFA1 and FFA4 significantly inhibited the effects of fish oil treatment in both dystrophic muscles. The anti-inflammatory effects of fish oil in dystrophic diaphragm muscle and heart were mediated through FFA1 and FFA4.

Anti-Inflammatory Effect of Simonsinol on Lipopolysaccharide Stimulated RAW264.7 Cells through Inactivation of NF-κB Signaling Pathway.

Simonsinol is a natural sesqui-neolignan firstly isolated from the bark of Illicium simonsii. In this study, the anti-inflammatory activity of simonsinol was investigated with a lipopolysaccharide (LPS)-stimulated murine macrophages RAW264.7 cells model. The results demonstrated that simonsinol could antagonize the effect of LPS on morphological changes of RAW264.7 cells, and decrease the production of nitric oxide (NO), tumor necrosis factor α (TNF-α), and interleukin 6 (IL-6) in LPS-stimulated RAW264.7 cells, as determined by Griess assay and enzyme-linked immunosorbent assay (ELISA). Furthermore, simonsinol could downregulate transcription of inducible nitric oxide synthase (iNOS), TNF-α, and IL-6 as measured by reverse transcription polymerase chain reaction (RT-PCR), and inhibit phosphorylation of the alpha inhibitor of NF-κB (IκBα) as assayed by Western blot. In conclusion, these data demonstrate that simonsinol could inhibit inflammation response in LPS-stimulated RAW264.7 cells through the inactivation of the nuclear transcription factor kappa-B (NF-κB) signaling pathway.

NLRC5 alleviated OGD/R-induced PC12-cell injury by inhibiting activation of the TLR4/MyD88/NF-κB pathway.

ObjectiveTo assess the role of NOD-like receptor C5 (NLRC5; a major NLRC family protein that regulates immunity, inflammation and tissue fibrosis), in cerebral ischemia-reperfusion injury, characterized by inflammation and oxidative damage.MethodsBlood NLRC5 levels were assessed in neonates with cerebral ischemia and in healthy controls. A stable PC12 cell line was established that overexpressed or knocked down NLRC5. Inflammatory responses, apoptosis rate and oxidative damage in PC12 cells under oxygen-glucose deprivation/reperfusion (OGD/R) conditions were evaluated using enzyme-linked immunosorbent assay (ELISA), terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL) and reactive oxygen species (ROS) assay.ResultsBlood NLRC5 levels were suppressed in neonates with cerebral ischemia. ELISAs showed that NLRC5 suppressed levels of tumour necrosis factor-α, interleukin (IL)-6, IL-1β, ROS and superoxide dismutase in OGD/R-treated PC12 cells. Furthermore, NLRC5 overexpression was associated with reduced apoptosis rate in PC12 cells treated by OGD/R. Overexpression of NLRC5 also inhibited levels of toll-like receptor (TLR)4, myeloid differentiation primary response protein MyD88 (MyD88) and phosphorylated nuclear factor kappa B-transcription factor p65 (NF-κB p-p65) in PC12 cells, and decreased nuclear levels of NF-κB p-p65.ConclusionNLRC5 alleviated inflammatory responses, oxidative damage and apoptosis in PC12 cells under OGD/R conditions by suppressing activation of the TLR4/MyD88/NF-κB pathway.