Grassfed beef - fat analysis - omega 6 to 3 ratio - D S Family Farm

«The previous blog post was a little heavy on charts (PDF with all charts) from the laboratory analysis of one of our pasture grazed ribeye steaks.  In this post I continue the comparison of our grassfed beef to two “typical” beef samples.  First of all let’s summarize some of the discussion and charts from the earlier post, then we will address polyunsaturated … Read More →»

2011 Potential beneficial effects of butyrate in intestinal and extraintestinal diseases

«The multiple beneficial effects on human health of the short-chain fatty acid butyrate, synthesized from non-absorbed carbohydrate by colonic microbiota, are well documented. At the intestinal level, butyrate plays a regulatory role on the transepithelial fluid transport, ameliorates mucosal inflammation and oxidative status, reinforces the epithelial defense barrier, and modulates visceral sensitivity and intestinal motility. In addition, a growing number of studies have stress the role of butyrate in the prevention and inhibition of colorectal cancer. At the extraintestinal level, butyrate exerts potentially useful effects on many conditions, including hemoglobinopathies, genetic metabolic diseases, hypercholesterolemia, insulin resistance, and ischemic stroke. The mechanisms of action of butyrate are different; many of these are related to its potent regulatory effects on gene expression. These data suggest a wide spectrum of positive effects exerted by butyrate, with a high potential for a therapeutic use in human medicine.»

2011 Omega-3 Supplementation Lowers Inflammation and Anxiety in Medical Students: A Randomized Controlled Trial

«Observational studies have linked lower omega-3 (n-3) polyunsaturated fatty acid (PUFA) and higher omega-6 (n-6) PUFA with inflammation and depression, but randomized controlled trial (RCT) data have been mixed. To determine whether n-3 decreases proinflammatory cytokine production and depressive and anxiety symptoms in healthy young adults, this parallel group, placebo-controlled, double-blind 12-week RCT compared n-3 supplementation with placebo. The participants, 68 medical students, provided serial blood samples during lower-stress periods as well as on days before an exam. The students received either n-3 (2.5 g/d, 2085 mg eicosapentaenoic acid and 348 mg docosahexanoic acid) or placebo capsules that mirrored the proportions of fatty acids in the typical American diet. Compared to controls, those students who received n-3 showed a 14% decrease in lipopolysaccharide (LPS) stimulated interleukin 6 (IL-6) production and a 20% reduction in anxiety symptoms, without significant change in depressive symptoms. Individuals differ in absorption and metabolism of n-3 PUFA supplements, as well as in adherence; accordingly, planned secondary analyses that used the plasma n-6:n-3 ratio in place of treatment group showed that decreasing n-6:n-3 ratios led to lower anxiety and reductions in stimulated IL-6 and tumor necrosis factor alpha (TNF-α) production, as well as marginal differences in serum TNF-α. These data suggest that n-3 supplementation can reduce inflammation and anxiety even among healthy young adults. The reduction in anxiety symptoms associated with n-3 supplementation provides the first evidence that n-3 may have potential anxiolytic benefits for individuals without an anxiety disorder diagnosis. ClinicalTrials.gov identifier: https://clinicaltrials.gov/ct2/show/NCT00519779" ref="reftype=extlink-clinical-trial&issue-id=200939&journal-id=319&FROM=Article%7CBody&TO=External%7CResource%7CClinical%20Trials%7CClinicalTrials.gov&rendering-type=normal">{"type":"clinical-trial","attrs":{"text":"NCT00519779","term_id":"NCT00519779"}}NCT00519779»

2013 Fisetin: A Dietary Antioxidant for Health Promotion

«Significance: Diet-derived antioxidant are now being increasingly investigated for their health-promoting effects, including their role in the chemoprevention of cancer. In general, botanical antioxidant have received much attention, as they can be consumed for longer periods of time without any adverse effects. Flavonoids are a broadly distributed class of plant pigments that are regularly consumed in the human diet due to their abundance. One such flavonoid, fisetin (3,3′,4′,7-tetrahydroxyflavone), is found in various fruits and vegetables, such as strawberry, apple, persimmon, grape, onion, and cucumber. Recent Advances: Several studies have demonstrated the effects of fisetin against numerous diseases. It is reported to have neurotrophic, anticarcinogenic, anti-inflammatory, and other health beneficial effects. Critical Issues: Although fisetin has been reported as an anticarcinogenic agent, further in-depth in vitro and in vivo studies are required to delineate the mechanistic basis of its observed effects. In this review article, we describe the multiple effects of fisetin with special emphasis on its anticancer activity as investigated in cell culture and animal models. Future Directions: Additional research focused toward the identification of molecular targets could lead to the development of fisetin as a chemopreventive/chemotherapeutic agent against cancer and other diseases. Antioxid. Redox Signal. 19, 151–162.»

2015 Low-certainty evidence was found that a reduction in unprocessed red meat intake of 3 servings per week is associated with a very small reduction in risk for cardiovascular mortality, stroke, myocardial infarction (MI), and type 2 diabetes. Likewise, low-certainty evidence was found that a reduction in processed meat intake of 3 servings per week is associated with a very small decrease in risk for all-cause mortality, cardiovascular mortality, stroke, MI, and type 2 diabetes. LIMITATION: Inadequate adjustment for known confounders, residual confounding due to observational design, and recall bias associated with dietary measurement. CONCLUSION: The magnitude of association between red and processed meat consumption and all-cause mortality and adverse cardiometabolic outcomes is very small, and the evidence is of low certainty.

We report that BHB, but neither acetoacetate nor structurally-related short chain fatty acids, butyrate and acetate, suppresses activation of the NLRP3 inflammasome in response to several structurally unrelated NLRP3 activators, without impacting NLRC4, AIM2 or non-canonical caspase-11 inflammasome activation. Mechanistically, BHB inhibits NLRP3 inflammasome by preventing K+ efflux and reducing ASC oligomerization and speck formation. The inhibitory effects of BHB on NLRP3 were not dependent on chirality or classical starvation regulated mechanisms like AMPK, reactive oxygen species (ROS), autophagy or glycolytic inhibition. BHB blocked NLRP3 inflammasome without undergoing oxidation in TCA cycle, independently of uncoupling protein-2 (UCP2), Sirt2, receptor Gpr109a and inhibition of NLRP3 did not correlate with magnitude of histone acetylation in macrophages. BHB reduced the NLRP3 inflammasome mediated IL-1β and IL-18 production in human monocytes. In vivo, BHB attenuates caspase-1 activation and IL-1β secretion in mouse models of NLRP3-mediated diseases like Muckle-Wells Syndrome (MWS), Familial Cold Autoinflammatory syndrome (FCAS) and urate crystal induce body cavity inflammation. Taken together, these findings suggest that the anti-inflammatory effects of caloric restriction or ketogenic diets may be mechanistically linked to BHB-mediated inhibition of the NLRP3 inflammasome, and point to the potential use of interventions that elevate circulating BHB against NLRP3-mediated proinflammatory diseases.

2015 Ginger and Its Constituents: Role in Prevention and Treatment of Gastrointestinal Cancer

a significant number of in vitro, in vivo, and epidemiological studies further provide substantial evidence that ginger and its active compounds are effective against wide variety of human diseases including GI cancer.

Ginger has been found to be effective against various GI cancer such as gastric cancer, pancreatic cancer, liver cancer, colorectal cancer, and cholangiocarcinoma.

2015 Frequency and Circadian Timing of Eating May Influence Biomarkers of Inflammation and Insulin Resistance Associated with Breast Cancer Risk

Each 10 percent increase in the proportion of calories consumed in the evening was associated with a 3 percent increase in CRP. Conversely, eating one additional meal or snack per day was associated with an 8 percent reduction in CRP.

2015 The Impact of Vitamin D Levels on Inflammatory Status: A Systematic Review of Immune Cell Studies

«Seven cell line studies (Table 1) were identified. Six out of the seven studies used the THP-1 cell line, while two studies used the U937 cell line and one study used Jurkat cells. All cell line studies administered vitamin D in the form of 1,25(OH)₂ and one study also used 25(OH)D. All studies except one administered vitamin D in conjunction with an inflammatory stimulus. Overall, the majority of cell line studies (4 out of 7) reported that vitamin D had an anti-inflammatory effect, one study reported mixed effects and two studies reported a pro-inflammatory effect. The most common concentration of 1,25(OH)₂ that indicated an anti-inflammatory effect was 10 nM (4 out of 7 studies). Mechanisms likely to mediate the anti-inflammatory effect of vitamin D included suppressed phosphorylated p38 (pp38) expression [40], reduced expression of p-STAT5 [41], and decreased reactive oxygen species levels due to increased cellular glutathione [42] (Fig 2).»

2016 Review of Anti-Inflammatory Herbal Medicines

«Medicinal plants and their secondary metabolites are progressively used in the treatment of diseases as a complementary medicine. Inflammation is a pathologic condition that includes a wide range of diseases such as rheumatic and immune-mediated conditions, diabetes, cardiovascular accident, and etcetera. We introduce some herbs which their anti-inflammatory effects have been evaluated in clinical and experimental studies. Curcuma longa, Zingiber officinale, Rosmarinus officinalis, Borago officinalis, evening primrose, and Devil's claw are some of the introduced medicinal herbs in this review. Since the treatment of inflammation is not a one-dimensional remedy, this review tries to reach a multidimensional therapeutic approach to inflammation with the help of herbal medicine and modification in lifestyle.»

2017 Antioxidant effects of resveratrol in the cardiovascular system

«The antioxidant effects of resveratrol (3,5,4'‐trihydroxy‐trans‐stilbene) contribute substantially to the health benefits of this compound. Resveratrol has been shown to be a scavenger of a number of free radicals. However, the direct scavenging activities of resveratrol are relatively poor. The antioxidant properties of resveratrol in vivo are more likely to be attributable to its effect as a gene regulator. Resveratrol inhibits NADPH oxidase‐mediated production of ROS by down‐regulating the expression and activity of the oxidase. This polyphenolic compound reduces mitochondrial superoxide generation by stimulating mitochondria biogenesis. Resveratrol prevents superoxide production from uncoupled endothelial nitric oxide synthase by up‐regulating the tetrahydrobiopterin‐synthesizing enzyme GTP cyclohydrolase I. In addition, resveratrol increases the expression of various antioxidant enzymes. Some of the gene‐regulating effects of resveratrol are mediated by the histone/protein deacetylase sirtuin 1 or by the nuclear factor‐E2‐related factor‐2. In this review article, we have also summarized the cardiovascular effects of resveratrol observed in clinical trials.»

2017 The Impact of Ghrelin in Metabolic Diseases: An Immune Perspective

«Obesity and insulin resistance have reached epidemic proportions. Obesogenic conditions are associated with increased risk for the development of other comorbidities and obesity-related diseases. In metabolic disorder, there is chronic low-grade inflammation induced by the activation of immune cells, especially in metabolic relevant organs such as white adipose tissue (WAT). These immune cells are regulated by environmental and systemic cues. Ghrelin is a peptide secreted mainly by X/A-like gastric cells and acts through the growth hormone secretagogue receptor (GH-R). This receptor is broadly expressed in the central nervous system (CNS) and in several cell types, including immune cells. Studies show that ghrelin induces an orexigenic state, and there is increasing evidence implicating an immunoregulatory role for ghrelin. Ghrelin mainly acts on the innate and adaptive immune system to suppress inflammation and induce an anti-inflammatory profile. In this review, we discuss the immunoregulatory roles of ghrelin, the mechanisms by which ghrelin acts and potential pharmacological applications for ghrelin in the treatment of obesity-associated inflammatory diseases, such as type 2 diabetes (T2D).»

«In vivo, ghrelin has an anti-inflammatory and antinociceptive role [13, 34, 37, 111, 115–118]. Intraperitoneal administration of ghrelin in rats submitted to pain resulted in increased levels of serum IL-10 and TGF-β and reduced pain score [118]. The anti-inflammatory action of ghrelin was also observed in a colitis model. Ghrelin treatment reduced the expression of TNF-α, INF-γ, IL-1α, IL-1β, IL-6, IL-12, IL-15, IL-17, and IL-18 and increased IL-10 levels in colonic mucosa, which improved colitis score and survival rate in mice [37].»

«The anti-inflammatory roles of ghrelin can be extended to other inflammatory conditions, such as rheumatoid arthritis. Administration of the ghrelin agonist growth hormone-releasing peptide-2 (GHRP-2) reduced serum IL-6 levels and improved inflammation in arthritic rats [119]. Similar observations were obtained when peritoneal macrophages were treated with GHRP-2 in vitro [119]. Together, this data indicates that GH-R can be used as a novel target for the treatment of acute and chronic inflammatory diseases»

2017 NF-κB signaling in inflammation

«The transcription factor NF-κB regulates multiple aspects of innate and adaptive immune functions and serves as a pivotal mediator of inflammatory responses. NF-κB induces the expression of various pro-inflammatory genes, including those encoding cytokines and chemokines, and also participates in inflammasome regulation. In addition, NF-κB plays a critical role in regulating the survival, activation and differentiation of innate immune cells and inflammatory T cells. Consequently, deregulated NF-κB activation contributes to the pathogenic processes of various inflammatory diseases. In this review, we will discuss the activation and function of NF-κB in association with inflammatory diseases and highlight the development of therapeutic strategies based on NF-κB inhibition.»

2018 Senolytics Improve Physical Function and Increase Lifespan in Old Age

«To test if senescent cells can directly cause physical dysfunction, we first transplanted senescent (SEN) or control, non-senescent (CON) preadipocytes (also termed adipocyte progenitors or adipose-derived stem cells²³) isolated from luciferase-expressing transgenic (LUC⁺) mice intraperitoneally into syngeneic, young (6-month-old) wild type (WT) animals (Fig. 1a). We induced cellular senescence using 10 Gray (Gy) radiation, which resulted in more than 85% of cells becoming senescent (Supplementary Fig. 1a,b). We transplanted preadipocytes because: 1) the SASP of radiation-induced senescent mouse preadipocytes (Supplementary Fig. 1c,d) resembles that of endogenous senescent cells with aging (Supplementary Fig. 1e)^20,24 and in idiopathic pulmonary fibrosis²⁵; 2) preadipocytes are less immunogenic or subject to rejection than other cell types²⁶; and 3) these cells are arguably the most abundant type of progenitors in humans²⁷ that are subject to cellular senescence. We also used doxorubicin to induce senescence to ascertain if the physiological impact of transplanted senescent cells is limited to the context of radiation-induced senescence: senescent cells induced by doxorubicin developed a SASP similar to that of radiation-induced senescent cells (Supplementary Fig. 1f). Five days after intraperitoneal transplantation of SEN or CON preadipocytes, the cells were mainly located in visceral fat (Fig. 1b,c and Supplementary Fig. 2a,b). Both the SEN and CON transplanted cells remained detectable by in vivo bioluminescence imaging (BLI) for up to 40 days (Supplementary Fig. 2c). Of note, we observed that senescent cells had higher luciferase activity than control non-senescent cells, even though they were from the same LUC transgenic mice (Supplementary Fig.2d).»

2018 Butyrate and Dietary Soluble Fiber Improve Neuroinflammation Associated With Aging in Mice

«Aging results in chronic systemic inflammation that can alter neuroinflammation of the brain. Specifically, microglia shift to a pro-inflammatory phenotype predisposing them to hyperactivation upon stimulation by peripheral immune signals. It is proposed that certain nutrients can delay brain aging by preventing or reversing microglial hyperactivation. Butyrate, a short-chain fatty acid (SCFA) produced primarily by bacterial fermentation of fiber in the colon, has been extensively studied pharmacologically as a histone deacetylase inhibitor and serves as an attractive therapeutic candidate, as butyrate has also been shown to be anti-inflammatory and improve memory in animal models. In this study, we demonstrate that butyrate can attenuate pro-inflammatory cytokine expression in microglia in aged mice. It is still not fully understood, however, if an increase in butyrate-producing bacteria in the gut as a consequence of a diet high in soluble fiber could affect microglial activation during aging. Adult and aged mice were fed either a 1% cellulose (low fiber) or 5% inulin (high fiber) diet for 4 weeks. Findings indicate that mice fed inulin had an altered gut microbiome and increased butyrate, acetate, and total SCFA production. In addition, histological scoring of the distal colon demonstrated that aged animals on the low fiber diet had increased inflammatory infiltrate that was significantly reduced in animals consuming the high fiber diet. Furthermore, gene expression of inflammatory markers, epigenetic regulators, and the microglial sensory apparatus (i.e., the sensome) were altered by both diet and age, with aged animals exhibiting a more anti-inflammatory microglial profile on the high fiber diet. Taken together, high fiber supplementation in aging is a non-invasive strategy to increase butyrate levels, and these data suggest that an increase in butyrate through added soluble fiber such as inulin could counterbalance the age-related microbiota dysbiosis, potentially leading to neurological benefits.»

2018 Fisetin is a senotherapeutic that extends health and lifespan

«We previously demonstrated that the flavonoid quercetin, an antioxidant, which also targets PI3 kinase delta as well as certain BCL-2 family members, reduces senescence in primary human umbilical vein endothelial cells (HUVECs) and murine embryonic fibroblasts (MEFs), especially when used in combination with the tyrosine kinase inhibitor dasatinib [30]. To determine if other flavonoids might have more potent senotherapeutic activity than quercetin, a panel of flavonoids was screened for effects on senescence induced by oxidative stress [49]. Primary MEFs from Ercc1^−/− mice were used. These cells undergo premature senescence if grown at atmospheric oxygen [56]. Ercc1^−/− MEF cultures were established at 3% O₂ then shifted to 20% O₂ for three passages to induce senescence. To quantify senescent cells, SA-ß-gal activity was measured using the fluorescent substrate C₁₂FDG [57] using an IN Cell Analyzer 6000 confocal imager. At a dose of 5 μM, fisetin was most effective in reducing the fraction of SA-ß-gal positive MEFs (Fig. 1A). Luteolin and curcumin also showed weak activity at a dose where quercetin was ineffective. In addition, fisetin reduced senescence in MEFs and IMR90 cells in a dose-dependent manner (Fig. 1B and C). These results are consistent with our previous finding that fisetin selectively reduces the viability of senescent HUVECs without affecting proliferating cells [32]. In HUVECs, fisetin induces apoptosis as measured by caspase3/7 activity, whereas in MEFs, fisetin suppressed markers of senescence without evidence of cell killing [32].»

2000 The I kappa B/NF-kappa B system: a key determinant of mucosalinflammation and protection.

«The ubiquitous transcription factor NF-kappa B is a central regulator of the transcriptional activation of a number of genes involved in cell adhesion, immune and proinflammatory responses, apoptosis, differentiation, and growth. Induction of these genes in intestinal epithelial cells (IECs) by activated NF-kappa B profoundly influences mucosal inflammation and repair. NF-kappa B activation requires the removal of I kappa B from NF-kappa B by inducible proteolysis, which liberates this transcription factor for migration to the nucleus, where it binds to kappa B-regulatory elements and induces transcription. I kappa B alpha degradation is incomplete and delayed in IECs, resulting in buffered responses to luminal stimuli. The stimulatory environment partially determines whether the effect of NF-kappa B is protective or deleterious for the host. kappa B-dependent proinflammatory gene expression, particularly chemokines, major histocompatibility complex class II antigens, and adhesion molecules may be extremely important in early protective responses to mucosal pathogens but, when dysregulated, could lead to the development of chronic inflammation, as seen in inflammatory bowel diseases. The key role of NF-kappa B in regulating expression of a number of proinflammatory genes makes this protein an attractive target for selective therapeutic intervention.»

2001 Efficacy and safety of freeze-dried cat's claw in osteoarthritis of the knee: mechanisms of action of the species Uncaria guianensis.

«Cat's claw had no deleterious effects on blood or liver function or other significant side-effects compared to placebo. Pain associated with activity, medical and patient assessment scores were all significantly reduced, with benefits occurring within the first week of therapy. Knee pain at rest or at night, and knee circumference were not significantly reduced by cat's claw during this brief trial. In vitro tests indicated that U guianensis and U. tomentosa were equivalent at quenching DPPH radicals (EC50, 13.6-21.7 microg/ml) as well as inhibiting TNFalpha production. However, the latter action was registered at much lower concentration (EC50, 10.2-10.9 ng/ml). Cat's claw (10 microg/ml) had no effect on basal PGE2 production, but reduced LPS-induced PGE2 release (P < 0.05), but at higher concentration than that required for TNFalpha inhibition.»

2002 Anti-inflammatory activity of two different extracts of Uncaria tomentosa (Rubiaceae).

«We assessed in vivo the anti-inflammatory activity of two Cat's claw bark extracts, by comparing a spray-dried hydroalcoholic extract against an aqueous freeze-dried extract, to determine which extract was more effective. We used the carrageenan-induced paw edema model in mice. In addition, to assess the molecular mechanism of action, we determined the inhibition of NF-kappa B through the Electrophoretic Mobility Shift Assay (EMSA) and the effects on cycloxygenase-1 and -2. Results showed that the anti-inflammatory activity was significantly higher using the hydroalcoholic compared with the aqueous extract (P<0.05). The extracts also showed little inhibitory activity on cyclooxygenase-1 and -2. It cannot be excluded that the slight inhibitory activity on DNA binding of NF-kappa B is due to cytotoxic effects.»

2008 Immunomodulating and antiviral activities of Uncaria tomentosa on human monocytes infected with Dengue Virus-2.

«Uncaria tomentosa (Willd.) DC., a large woody vine native to the Amazon and Central American rainforests has been used medicinally by indigenous peoples since ancient times and has scientifically proven immunomodulating, anti-inflammatory, cytotoxic and antioxidant activities. Several inflammatory mediators that are implicated in vascular permeability and shock are produced after Dengue Virus (DENV) infection by monocytes, the primary targets for virus replication. Here we assessed the immunoregulatory and antiviral activities from U. tomentosa-derived samples, which were tested in an in vitro DENV infection model. DENV-2 infected human monocytes were incubated with U. tomentosa hydro-alcoholic extract or either its pentacyclic oxindole alkaloid-enriched or non-alkaloid fractions. The antiviral activity was determined by viral antigen (DENV-Ag) detection in monocytes by flow cytometry. Our results demonstrated an in vitro inhibitory activity by both extract and alkaloidal fraction, reducing DENV-Ag+ cell rates in treated monocytes. A multiple microbead immunoassay was applied for cytokine determination (TNF-alpha, IFN-alpha, IL-6 and IL-10) in infected monocyte culture supernatants. The alkaloidal fraction induced a strong immunomodulation: TNF-alpha and IFN-alpha levels were significantly decreased and there was a tendency towards IL-10 modulation. We conclude that the alkaloidal fraction was the most effective in reducing monocyte infection rates and cytokine levels. The antiviral and immunomodulating in vitro effects from U. tomentosa pentacyclic oxindole alkaloids displayed novel properties regarding therapeutic procedures in Dengue Fever and might be further investigated as a promising candidate for clinical application.»

2008 Synergistic effect of combination of phenethyl isothiocyanate and sulforaphane or curcumin and sulforaphane in the inhibition of inflammation.

«Accumulating evidence from epidemiologic and clinical studies indicates that chronic inflammatory disorders harbor an increased risk of cancer development. Curcumin (CUR) has been strongly linked to the anti-inflammatory effect. On the other hand, isothiocyanates such as sulforaphane (SFN) and phenethyl isothiocyanate (PEITC) are strong phase-II detoxifying/antioxidant enzymes inducer. Therefore it is interesting to see if combination of these drugs can inhibit inflammation with higher combined efficacies.»

«We report that combination of PEITC + SFN or CUR + SFN has a synergistic effect in down-regulating inflammation markers like TNF, IL-1, NO, PGE2. The synergism is probably due to the synergistic induction of phase II/antioxidant enzymes including heme-oxygenase1 (HO-1) and NAD(P)H:quinone oxidoreductase 1 (NQO-1).»

2008 A plant flavonoid fisetin induces apoptosis in colon cancer cells by inhibition of COX2 and Wnt/EGFR/NF-kappaB-signaling pathways.

«Overexpression of cyclooxygenase 2 (COX2) and uncontrolled wingless and Int (Wnt)-signaling pathway have long been suggested to play crucial roles in colorectal cancer. Studies show that selective COX2 inhibitors possess great potential as chemopreventive agents for colon cancer. Recent studies suggest that targeting COX2 and epidermal growth factor receptor (EGFR) may provide better therapeutic strategy than inhibiting either single target and that this may alleviate the problem of COX2 inhibitor-associated side effects. Therefore, there have been intensive efforts to develop novel dietary substances that target COX2 and EGFR activation. Fisetin is a naturally occurring flavonoid commonly found in various vegetables and fruits. We found that the treatment of COX2-overexpressing HT29 human colon cancer cells with fisetin (30-120 microM) resulted in induction of apoptosis, downregulation of COX2 protein expression without affecting COX1 and inhibited the secretion of prostaglandin E2. Treatment of cells with fisetin also inhibited Wnt-signaling activity through downregulation of beta-catenin and T cell factor 4 and decreased the expression of target genes such as cyclin D1 and matrix metalloproteinase 7. Fisetin treatment of cells also inhibited the activation of EGFR and nuclear factor-kappa B (NF-kappaB). Finally, the formation of colonies in soft agar was suppressed by fisetin treatment. Taken together, we provide evidence that the plant flavonoid fisetin can induce apoptosis and suppress the growth of colon cancer cells by inhibition of COX2- and Wnt/EGFR/NF-kappaB-signaling pathways. We suggest that fisetin could be a useful agent for prevention and treatment of colon cancer.»

2009 Ghrelin inhibits the development of acute pancreatitis and nuclear factor kappaB activation in pancreas and liver.

«Ghrelin inhibits the development of acute pancreatitis induced by sodium taurocholate. It exerts the therapeutic effects through inhibiting NF-kappaB expression, thereby blocks the inflammatory signal transduction pathway and reduces the release of inflammatory media and cytokines.»

2010 Antioxidant and anti-inflammatory effects of resveratrol in airway disease.

«Respiratory diseases, such as asthma and chronic obstructive pulmonary disease (COPD), are a significant and increasing global health problem. These diseases are characterized by airway inflammation, which develops in response to various stimuli. In asthma, inflammation is driven by exposure to a variety of triggers, including allergens and viruses, which activate components of both the innate and acquired immune response. In COPD, exposure to cigarette smoke is the primary stimulus of airway inflammation. Activation of airway inflammatory cells lead to the release of excessive quantities of reactive oxygen species (ROS), resulting in oxidative stress. Antioxidant provide protection against the damaging effects of oxidative stress and thus may be useful in the management of inflammatory airways disease. Resveratrol, a polyphenol that demonstrates both antioxidative and anti-inflammatory functions, has been shown to improve outcomes in a variety of diseases, in particular, in cancer. We review the evidence for a protective role of resveratrol in respiratory disease. Mechanisms of resveratrol action that may be relevant to respiratory disease are described. We conclude that resveratrol has potential as a therapeutic agent in respiratory disease, which should be further investigated.»

2010 Sulforaphane activates heat shock response and enhances proteasome activity through up-regulation of Hsp27.

The major mechanism by which SFN, an electrophile, protects cells is believed to be through induction of direct and indirect antioxidant response, including up-regulation of glutathione and activation of
NF-E2-related factor 2 (Nrf2)-mediated phase II enzymes and
antioxidant enzymes that relieve cells from oxidant stress and carcinogenic attacks (11)

. However, its chemopreventive activity also includes other mechanisms, such as induction of cell cycle arrest and apoptotic pathways, inhibition of angiogenesis, and anti-inflammatory activity (9). Recently, SFN has been shown to enhance mammalian proteasome activity through induction of 26 S proteasome subunit PSMB5 (13). Both induction of PSMB5 and proteasome activation have been associated with antioxidant response mediated through the Keap1-Nrf2
pathway (13–16).

2012 The modifying effects of fish oil on fasting ghrelin mRNA expression in weaned rats.

«Ghrelin expression and secretion seem to be influenced by the fat content of the diet. However, data on the probable adverse effect of high fat diet (HFD) with different dietary fats and saturation level of fatty acids is inconclusive. This study aimed at investigating the effects of HFDs on fasting total and acyl-ghrelin plasma levels, gastric fundus and duodenum ghrelin mRNA expressions. Weaned Wistar rats (n=50) were randomly divided to five groups of HFDs with fish oil (HF-F), olive oil (HF-O), soy oil (HF-S), butter (HF-B) and the controls. After 8 weeks, blood samples were collected. While the animals were fasting for 24h, their blood and tissue samples were obtained. Plasma parameters of total and acyl ghrelin and ghrelin mRNA expression level in stomach and duodenum were measured. The HF-B fed group had lower fasting plasma acyl ghrelin level than the control, HF-F and HF-O groups (P<0.05); furthermore, the HF-F group had significantly higher acyl ghrelin level than the HF-S one (P<0.05). After feeding, all the groups, except for the HF-B one, had a significantly lower plasma acyl ghrelin levels (P<0.05), compared with the fasting state. Ghrelin mRNA expression levels in the gastric fundus and duodenum were significantly lower in the HF-B as compared to the control group. Furthermore, the HF-F group had significantly higher mRNA level in the duodenum, in comparison with the HF-B and HF-S groups. As HF-F and HF-O diets had the highest stimulatory effect on fasting ghrelin expression and plasma level, consumption of these dietary oils can play an important role in ghrelin regulation, which might affect feeding behavior and energy intake.»

2012 The ghrelin O-acyltransferase-ghrelin system reduces TNF-α-induced apoptosis and autophagy in human visceral adipocytes.

«Circulating concentration of acylated ghrelin and TNF-α were increased, whereas desacyl ghrelin levels were decreased in obesity-associated type 2 diabetes. Ghrelin and GOAT were produced in omental and subcutaneous adipose tissue. Visceral adipose tissue from obese patients with type 2 diabetes showed higher levels of GOAT, increased adipocyte apoptosis and increased expression of the autophagy-related genes ATG5, BECN1 and ATG7. In differentiating human omental adipocytes, incubation with acylated and desacyl ghrelin reduced TNF-α-induced activation of caspase-8 and caspase-3, and cell death. In addition, acylated ghrelin reduced the basal expression of the autophagy-related genes ATG5 and ATG7, while desacyl ghrelin inhibited the TNF-α-induced increase of ATG5, BECN1 and ATG7 expression.»

2013 Anti-inflammatory and antioxidant effects of resveratrol in healthy smokers a randomized, double-blind, placebo-controlled, cross-over trial.

«Because resveratrol has anti-inflammatory, anti-oxidant, and hypotriglyceridemic effects, its supplementation may beneficially affect the increased cardiovascular risk of healthy smokers.»

2013 TNF-α signalling and inflammation: interactions between old acquaintances.

This review concisely summarizes the role of this pro-inflammatory cytokine during inflammation. It is focused mainly on TNF-α intracellular signaling and its influence on the typical inflammatory features in the organism. Being one of the most important pro-inflammatory cytokines, TNF-α participates in vasodilatation and edema formation, and leukocyte adhesion to epithelium through expression of adhesion molecules; it regulates blood coagulation, contributes to oxidative stress in sites of inflammation, and indirectly induces fever. The connection between TNF-α and cancer is mentioned as well.

2013 The polyphenol fisetin protects bone by repressing NF-κB and MKP-1-dependent signaling pathways in osteoclasts.

«Osteoporosis is a bone pathology leading to increase fractures risk and challenging quality of life. Since current treatments could exhibit deleterious side effects, the use of food compounds derived from plants represents a promising innovative alternative due to their potential therapeutic and preventive activities against human diseases. In this study, we investigated the ability of the polyphenol fisetin to counter osteoporosis and analyzed the cellular and molecular mechanisms involved. In vivo, fisetin consumption significantly prevented bone loss in estrogen deficiency and inflammation mice osteoporosis models. Indeed, bone mineral density, micro-architecture parameters and bone markers were positively modulated by fisetin. Consistent with in vivo results, we showed that fisetin represses RANKL-induced osteoclast differentiation and activity as demonstrated by an inhibition of multinucleated cells formation, TRAP activity and differentiation genes expression. The signaling pathways NF-κB, p38 MAPK, JNK and the key transcription factors c-Fos and NFATc1 expressions induced by RANKL, were negatively regulated by fisetin. We further showed that fisetin inhibits the constitutive proteasomal degradation of MKP-1, the phosphatase that deactivates p38 and JNK. Consistently, using shRNA stable cell lines, we demonstrated that impairment of MKP-1 decreases fisetin potency. Taken together, these results strongly support that fisetin should be further considered as a bone protective agent.»

2013 Curcumin improves expression of ghrelin through attenuating oxidative stress in gastric tissues of streptozotocin-induced diabetic gastroparesis rats.

«The study was performed to investigate the improved effect of curcumin on gastrointestinal function in streptozotocin-induced diabetic rats. Curcumin was administrated intragastrically at a dose of 100, 200 and 400 mg/kg/day to diabetic rats. After 28 days of treatment, the activity of superoxide dismutase (SOD), catalase (CAT), the content of reduced glutathione (GSH) and malondialdehyde (MDA) in gastric mucosa was assayed. Furthermore, the gastric function was evaluated by hormone secretion and gastric emptying tests. The results indicated that: (i) the diabetic rats exhibited significant decreases in the above mentioned antioxidative enzymes activities and GSH level and exhibited a high level of MDA. After administration of curcumin, the parameters were ameliorated to a large extent; (ii) curcumin treatment dose-dependently augmented the ghrelin levels of stomach and plasma, which were earlier depleted in the diabetic control rats. Conversely, the expression of ghrelin mRNA was decreased after curcumin treatment; and (iii) the gastric emptying in curcumin treated diabetic rats was notably accelerated compared with the diabetic control rats. These findings showed an improved effect of curcumin against streptozotocin-induced gastroparesis possibly by its antioxidant property.»

2013 Canonical Nlrp3 inflammasome links systemic low-grade inflammation to functional decline in aging.

Consistent with the hypothesis that systemic low-grade inflammation promotes age-related degenerative changes, the deficient Nlrp3 inflammasome-mediated caspase-1 activity improved glycemic control and attenuated bone loss and thymic demise. Notably, IL-1 mediated only Nlrp3 inflammasome-dependent improvement in cognitive function and motor performance in aged mice. These studies reveal Nlrp3 inflammasome as an upstream target that controls age-related inflammation and offer an innovative therapeutic strategy to lower Nlrp3 activity to delay multiple age-related chronic diseases. Although, it remains unknown whether reduction in Nlrp3 activation can extend lifespan, our data demonstrate unequivocally that deletion of Nlrp3 inflammasome enhances healthspan and prevents functional decline in multiple organs, including protection against thymic demise, cataract development, glucose intolerance and also enhances cortical and trabecular bone mass.

2014 The cholinergic anti-inflammatory pathway: a critical review.

« inflammatory response is being mediated via acetylcholine signals through the microvilli connecting the mesothelial cells and the organ they line»

2015 Bicarbonate-sensitive calcification and lifespan of klotho-deficient mice.

«Klotho, a protein counteracting aging, is a powerful inhibitor of 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] formation and regulator of mineral metabolism. In klotho hypomorphic (kl/kl) mice, excessive 1,25(OH)2D3 formation lead to hypercalcemia, hyperphosphatemia and vascular calcification, severe growth deficits, accelerated aging and early death. Kl/kl mice further suffer from extracellular volume depletion and hypotension, leading to the stimulation of antidiuretic hormone and aldosterone release. A vitamin D-deficient diet, restriction of dietary phosphate, inhibition of mineralocorticoid receptors with spironolactone, and dietary NaCl all extend the lifespan of kl/kl mice. Kl/kl mice suffer from acidosis. The present study explored whether replacement of tap drinking water by 150 mM NaHCO3 affects the growth, tissue calcification, and lifespan of kl/kl mice. As a result, NaHCO3 administration to kl/kl mice did not reverse the growth deficit but substantially decreased tissue calcification and significantly increased the average lifespan from 78 to 127 days. NaHCO3 did not significantly affect plasma concentration of 1,25(OH)2D3 and Ca(2+) but significantly decreased plasma phosphate concentration and plasma aldosterone concentration. The present study reveals a novel effect of bicarbonate, i.e., a favorable influence on vascular calcification and early death of klotho-deficient mice.»

2017 Eicosapentaenoic acid and docosahexaenoic acid containing supplements modulate risk factors for cardiovascular disease: a meta-analysis of randomis...

«RESULTS: Compared with control, EPA and DHA supplements produced significant reductions of triglycerides of 0.368 mmol L^-1 [95% confidence interval (CI) = -0.427 to -0.309], systolic blood pressure of 2.195 mmHg (95% CI = -3.172 to -1.217), diastolic blood pressure of 1.08 mmHg (95% CI = -1.716 to -0.444), heart rate of 1.37 bpm (95% CI = -2.41 to -0.325) and C-reactive protein of 0.343 mg L^-1 (95% CI = -0.454 to -0.232). This analysis indicates an increase in both low-density lipoprotein cholesterol (mean difference = 0.150 mmol L^-1 ; 95% CI = 0.058-0.243) and high-density lipoprotein cholesterol (mean difference = 0.039 mmol L^-1 ; 95% CI = 0.024-0.054). The triglyceride-lowering effect was dose-dependent.

CONCLUSIONS: The lipid-lowering, hypotensive, anti-arrhythmic and anti-inflammatory actions of EPA and DHA supplements were confirmed in this analysis of randomised placebo-control blinded clinical trials.»

2017 Omega-3 fatty acids and inflammatory processes: from molecules to man.

«Inappropriate, excessive or uncontrolled inflammation contributes to a range of human diseases. Inflammation involves a multitude of cell types, chemical mediators and interactions. The present article will describe nutritional and metabolic aspects of omega-6 (n-6) and omega-3 (n-3) fatty acids and explain the roles of bioactive members of those fatty acid families in inflammatory processes. Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are n-3 fatty acids found in oily fish and fish oil supplements. These fatty acids are capable of partly inhibiting many aspects of inflammation including leucocyte chemotaxis, adhesion molecule expression and leucocyte-endothelial adhesive interactions, production of eicosanoids like prostaglandin and leukotrienes from the n-6 fatty acid arachidonic acid and production of pro-inflammatory cytokines. In addition, EPA gives rise to eicosanoids that often have lower biological potency than those produced from arachidonic acid, and EPA and DHA give rise to anti-inflammatory and inflammation resolving mediators called resolvins, protectins and maresins. Mechanisms underlying the anti-inflammatory actions of EPA and DHA include altered cell membrane phospholipid fatty acid composition, disruption of lipid rafts, inhibition of activation of the pro-inflammatory transcription factor nuclear factor κB so reducing expression of inflammatory genes and activation of the anti-inflammatory transcription factor peroxisome proliferator-activated receptor γ. Animal experiments demonstrate benefit from EPA and DHA in a range of models of inflammatory conditions. Human trials demonstrate benefit of oral n-3 fatty acids in rheumatoid arthritis and in stabilizing advanced atherosclerotic plaques. Intravenous n-3 fatty acids may have benefits in critically ill patients through reduced inflammation. The anti-inflammatory and inflammation resolving actions of EPA, DHA and their derivatives are of clinical relevance.»

2017 Fisetin Regulates Nrf2 Expression and the Inflammation-Related Signaling Pathway to Prevent UVB-Induced Skin Damage in Hairless Mice.

«Our results demonstrate that fisetin attenuates UVB-induced damage, oxidative stress,
inflammation, and skin barrier function disruption. Fisetin inhibits the UVB-induced expression of MMP, COX-2, IL-6, and NF-κB, thus protecting the skin from wrinkles and erythema. Fisetin also
increases the expression of Nrf2 in the mice skin. In addition, fisetin effectively inhibits UV-induced aquaporin and filaggrin damage. The present study demonstrates the protective effects of fisetin against UV-induced skin damage.»

2017 Role of D-galactose-induced brain aging and its potential used for therapeutic interventions.

The effects of D-galactose-induced mitochondrial dysfunction and oxidative stress in the brain. D-galactose oxidized by galactose oxidase to form hydrogen peroxide (H2O2), leading to decrease in superoxide dismutase (SOD) (Hsieh et al., 2009). Increased H2O2 reacts with a reduced form of iron (Fe) to form hydroxide ions (OH-). The H2O2 and OH are both types of reactive oxygen species (ROS) and along with others can cause lipid peroxidation in the cell membranes and impair redox homeostasis, leading to neuronal damage.

In addition, several studies described that D-galactose induced the accumulation of brain mitochondrial DNA mutation (Chen et al., 2011; Du et al., 2012; Du et al., 2015; Zeng et al., 2014) through: 1) decreasing DNA-repairing enzymes (OGG1, pol ᵧ) (Chen et al., 2011), and 2) common deletion of mitochondrial DNA and impairing mitochondrial structures via the NOX-dependent pathway (Du et al., 2015).

Effect of D-galactose-induced apoptosis in the brain. D-galactose
promoted the apoptotic process (Qian et al., 2008). In addition to apoptosis, D-galactose promoted neuro-inflammation and neurodegeneration (Cui et al., 2006). The dosage from which D-galactose started inducing apoptosis was 100 mg- 500 mg/kg/day, duration was from 6 weeks to 9 weeks. (as shown in Table 2)

Effect of D-galactose-induced brain inflammation. D-galactose started inducing inflammation at a dosage of 50mg-180mg/kg/day and duration was from 6 weeks to 60 days.

Therapeutic approaches to brain mitochondrial aging induced by D-galactose:

The first one used R-alpha-lipoic acid which is an antioxidant abundant in yeast, liver, kidney, spinach, broccoli, and potatoes, to treat mitochondrial dysfunction (Long et al., 2007). One of the studies stated that 100 mg/kg/day of R-alpha-lipoic acid is used for prevention but not for intervention, dosage should be increased up to 180mg/kg/day (Inman et al., 2013).

Carvidilol, pioglitazone, curcumin and hesperidin have an antioxidant effect. These drugs have been used as an intervention to reverse D-galactose-induced mitochondrial dysfunction in a dose dependent manner.

The other therapeutic approaches to improve cognition with a dose-independent manner in the D-galactose model were fibroblast growth factor 21 (FGF21), salidroside, and tetrahydropalmatine (Banji et al., 2014; Gao et al., 2015; Kumar et al., 2009; Prakash and Kumar, 2013; Qu et al., 2016; Yang et al., 2016; Yu et al., 2015).

FGF21 acts on its receptors and prevents D-galactose-induced spatial learning and memory impairment by attenuating oxidative stress, inflammatory markers and renovating the activities of antioxidant enzymes and decreasing AGE formation, and TChE activity (Yu et al., 2015).

Many studies have proved that a daily intake of caffeine ameliorated cognitive decline in “non-demented” elderly men and women by the mechanism of reducing synaptic dysfunction, and the reduction in oxidative stress, apoptosis, neuro-inflammation and neurodegeneration (Ritchie et al., 2007; van Gelder et al., 2007).

2018 TNF-α inhibits SCF, ghrelin, and substance P expressions through the NF-κB pathway activation in interstitial cells of Cajal.

«Ulcerative colitis is a chronic inflammatory disease of the colon where intestinal motility is disturbed. Interstitial cells of Cajal (ICC) are required to maintain normal intestinal motility. In the present study, we assessed the effect of tumor necrosis factor-alpha (TNF-α) on viability and apoptosis of ICC, as well as on the expression of stem cell factor (SCF), ghrelin, and substance P. ICC were derived from the small intestines of Swiss albino mice. Cell viability and apoptosis were measured using CCK-8 assay and flow cytometry, respectively. ELISA was used to measure the concentration of IL-1β, IL-6, ghrelin, substance P, and endothelin-1. Quantitative RT-PCR was used to measure the expression of SCF. Western blotting was used to measure the expression of apoptosis-related proteins, interleukins, SCF, and NF-κB signaling pathway proteins. TNF-α induced inflammatory injury in ICC by decreasing cell viability and increasing apoptosis and levels of IL-1β and IL-6. TNF-α decreased the levels of SCF, ghrelin, and substance P, but had no effect on endothelin-1. TNF-α down-regulated expressions of SCF, ghrelin, and substance P by activating the NF-κB pathway in ICC. In conclusion, TNF-α down-regulated the expressions of SCF, ghrelin, and substance P via the activation of the NF-κB pathway in ICC.»

2018 Ageing: Is there a role for arachidonic acid and other bioactive lipids? A review.

Ageing is inevitable. Recent studies suggest that it could be delayed. Low-grade systemic inflammation is seen in type 2 diabetes mellitus, hypertension and endothelial dysfunction that are common with increasing age. In all these conditions, an alteration in arachidonic acid (AA) metabolism is seen in the form of increased formation of pro-inflammatory eicosanoids and decreased production of anti-inflammatory lipoxins, resolvins, protectins and maresins and decreased activity of desaturases. Calorie restriction, exercise and parabiosis delay age-related changes that could be related to enhanced proliferation of stem cells, decrease in inflammation and transfer of GDF-11 (growth differentiation factor-11) and other related molecules from the young to the old, increase in the formation of lipoxin A4, resolvins, protectins and maresins, hydrogen sulfide (H2S) and nitric oxide (NO); inhibition of ageing-related hypothalamic or brain IKK-β and NF-kB activation, decreased gonadotropin-releasing hormone (GnRH) release resulting in increased neurogenesis and consequent decelerated ageing. This suggests that hypothalamus participates in ageing process. N-acylethanolamines (NAEs) and lipid-derived signalling molecules can be tuned favorably under dietary restriction to extend lifespan and/or prevent advanced age associated diseases in an mTOR dependent pathway manner. Sulfur amino acid (SAA) restriction increased hydrogen sulfide (H2S) production and protected tissues from hypoxia and tissue damage. Anti-inflammatory metabolites formed from AA such as LXA4, resolvins, protectins and maresins enhance production of NO, CO, H2S; suppress NF-kB expression and alter mTOR expression and thus, may aid in delaying ageing process. Dietary restriction and exercise enhance AA metabolism to form LXA4, resolvins, protectins and maresins that have anti-inflammatory actions. AA and their metabolites also influence stem cell biology, enhance neurogenesis to improve memory and augment autophagy to prolong life span. Thus, AA and other PUFA and their anti-inflammatory metabolites inhibit inflammation, augment stem cell proliferation, restore to normal lipid-derived signaling molecules and NO and H2S production, enhance autophagy and prolong life span.

2018 Ghrelin Reduces TNF-α-Induced Human Hepatocyte Apoptosis, Autophagy, and Pyroptosis: Role in Obesity-Associated NAFLD.

«Ghrelin constitutes a protective factor against hepatocyte cell death. The increased acylated/desacyl ghrelin ratio in patients with obesity and NAFLD might constitute a compensatory mechanism to overcome TNF-α-induced hepatocyte apoptosis, autophagy, and pyroptosis.»

2018 Administration of hydrogen-rich water prevents vascular aging of the aorta in LDL receptor-deficient mice.

«The main cause of arteriosclerosis is atherosclerosis in the aorta. Atherosclerosis is recognized as a chronic inflammatory condition that begins with the dysfunction or activation of arterial endothelium. Low-density lipoprotein (LDL) and especially its oxidized form play a key role in endothelial dysfunction and atherogenesis. Recent studies showed that senescent cells are involved in the development and progression of atherosclerosis, and eliminating senescent cells suppresses the senescence-associated secretory phenotype. We previously reported that molecular hydrogen-rich water (HW) has antioxidant and anti-inflammatory effects in numerous diseases. Here, we used LDL receptor-deficient mice fed a high-fat diet (HFD) for 13 weeks as a model for atherosclerosis and evaluated the effects of continuous administration of HW. The numbers of endothelial cells in the atheroma expressing the senescence factors p16^INK4a and p21 decreased in HFD-fed mice given HW compared with HFD-fed mice given control water. Furthermore, macrophage infiltration and Tnfα expression in the atheroma were also suppressed. These results suggest that vascular aging can be suppressed by HW.»

2019 Network Meta-Analysis of Metabolic Effects of Olive-Oil in Humans Shows the Importance of Olive Oil Consumption With Moderate Polyphenol Levels as ...

«The beneficial role of olive oil consumption is nowadays widely recognized. However, it is not clear whether its health effects are due to the presence of monounsaturated lipids and/or to the antioxidant fraction of microconstituents present in olive oil. The aim of the present study was to analyze the exact role of olive oil in the modification of metabolic factors (glucose and circulating lipids) and explore the role of its antioxidant polyphenols. In the present work, we have performed a network meta-analysis of 30 human intervention studies, considering direct and indirect interactions and impact of each constituent. Interestingly, we show that the impact of olive oil on glucose, triglycerides, and LDL-cholesterol is mediated through an adherence to the Mediterranean diet, with the only notable effect of olive oil polyphenols being the increase of HDL-cholesterol, and the amelioration of the antioxidant and inflammatory status of the subjects. Additionally, we report for the first time that lower antioxidant polyphenol levels may be sufficient for the beneficial effects of olive oil, while we show that the lipid fraction of olive oil may be responsible for some of its beneficial actions. In all parameters examined the beneficial effect of olive oil was more pronounced in subjects with an established metabolic syndrome or other chronic conditions/diseases. In conclusion, all these findings provide new knowledge that could lead to re-establishment of the role of olive oil in human nutrition.»

1995 TNF-induced activation of NF-kappa B.

«Tumor Necrosis Factor (TNF) is one of the most potent physiological inducers of the nuclear transcription factor NF-kappa B. In light of the pivotal role of NF-kappa B in the development of immune response and activation of HIV replication, the identification of TNF signal transduction pathways involved in NF-kappa B activation is of particular interest. Data from our laboratory demonstrate that the TNF signal transduction pathway-mediating NF-kappa B activation involves two phospholipases, a phosphatidylcholine-specific phospholipase C (PC-PLC) and an endosomal acidic sphingomyelinase (aSMase). The aSMase activation by TNF is secondary to the generation of 1,2-diacylglycerol (DAG) produced by a TNF-responsive PC-PLC. SMase and its product ceramide induce degradation of the NF-kappa B inhibitor I kappa B as well as NF-kappa B activation. Besides endosomal acidic SMase, TNF also rapidly activates a plasmamembrane-associated neural SMase (nSMase), that, however is not involved in TNF-induced NF-kappa B activation. NSMase and aSMase are activated by different cytoplasmic domains of the 55 kDa TNF-receptor and are coupled to select pathways of TNF signaling. Ceramide generated by nSMase directs the activation of proline-directed serin/threonine protein kinase and phospholipase A2 and ceramide produced by aSMase triggers the activation of NF-kappa B. No apparent crosstalk was detected between nSMase and aSMase pathways, indicating that ceramide action depends on the topology of its production.»

1999 Antiinflammatory actions of cat's claw: the role of NF-kappaB.

«Cat's claw protects cells against oxidative stress and negated the activation of NF-kappaB. These studies provide a mechanistic evidence for the widely held belief that cat's claw is an effective anti-inflammatory agent.»

Сульфорафан и увеличение продолжительности жизни человека - YouTube

«Лектор - Евгения Малышева. Die eerste vijf levensjaren (gerekend vanaf de bevruchting) blijken ongelofelijk belangrijk voor de ontwikkeling van ons skelet. С...»

Сульфорафан и увеличение продолжительности жизни человека - YouTube

«Лектор - Евгения Малышева. Die eerste vijf levensjaren (gerekend vanaf de bevruchting) blijken ongelofelijk belangrijk voor de ontwikkeling van ons skelet. С...»