Lycopene‐derived bioactive retinoic acid receptors/retinoid‐X receptors‐activating metabolites may be relevant for lycopene's anti‐cancer potential

Dietary consumption of tomato products and especially the red tomato pigment lycopene has been associated with lower risk of cancer. New evidence is emerging toward metabolic pathways mediating the anti‐cancer activities of lycopene. In this review, we explore associations between tomatoes and lycopene intake and cancer and relate this to the metabolic activation pathways of lycopene via carotene oxygenases and further carotenoid/retinoid‐metabolizing enzymes to apo‐lycopenoids. Several of these apo‐lycopenoids have already been identified but up to date no direct connection between lycopene metabolism and apo‐lycopenoids mediated receptor activation pathways has been established. Retinoic acid receptors/retinoid‐X receptors activation pathways in particular, may be mediated via lycopene metabolites that are related to retinoic acids. Various studies have shown an association between lower concentration of insulin‐like growth factor‐1 upon lycopene treatment, cancer incidences, and retinoid‐mediated signaling. In this review, we interrelate tomato/lycopene ingestion and cancer incidence, with metabolic activation of lycopene and retinoid‐mediated signaling. The aim is to discuss a potential mechanism to explain lycopene related anti‐cancer activities by modulation of insulin‐like growth factor‐1 concentrations via lycopene metabolite activation of retinoid‐mediated signaling.     

The importance of GLP‐1 and PYY in resistant starch's effect on body fat in mice

Resistant starch (RS) is a dietary fermentable fiber that decreases body fat accumulation, and stimulates the secretion of glucagon‐like peptide‐1 (GLP‐1) and peptide YY (PYY) in rodents. GLP‐1 and PYY are gut‐secreted hormones with antiobesity effect. Thus, blocking the signals of increased GLP‐1 and PYY may also block the effect of dietary RS on body fat. In a 10‐week study, C57BL/6J and GLP‐1 receptor null (GLP‐1R KO) mice were fed control or 30% RS diet, and received daily intraperitoneal injection of either saline or PYY receptor antagonist (BIIE0246, 20 μg/kg body weight). Dietary RS significantly decreased body fat accumulation only in wild‐type mice that has saline injection, but not in GLP‐1R KO mice. PYY receptor antagonist diminished RS action on body fat in wild‐type mice, but did not interfere with GLP‐1R KO mice response to RS. Regardless of genotype and injection received, all RS‐fed mice had increased cumulative food intake, cecal fermentation, and mRNA expression of proglucagon and PYY. Thus, our results suggest that increased GLP‐1 and PYY is important in RS effects on body fat accumulation.     

Aromatic‐Turmerone Attenuates LPS‐Induced Neuroinflammation and Consequent Memory Impairment by Targeting TLR4‐Dependent Signaling Pathway

Scope : Curcuma longa (turmeric) is a folk medicine in South and Southeast Asia, which has been widely used to alleviate chronic inflammation. Aromatic‐turmerone is one of the main components abundant in turmeric essential oil. However, little information is available from controlled studies regarding its biological activities and underlying molecular mechanisms against chronic inflammation in the brain. In the current study, we employed a classical LPS model to study the effect and mechanism of aromatic‐turmerone on neuroinflammation. Methods and results : The effects of aromatic‐turmerone were studied in LPS‐treated mice and BV2 cells. The cognitive function assays, protein analyses, and histological examination were performed. Oral administration of aromatic‐turmerone could reverse LPS‐induced memory disturbance and normalize glucose intake and metabolism in the brains of mice. Moreover, aromatic‐turmerone significantly limited brain damage, through inhibiting the activation of microglia and generation of inflammatory cytokines. Further study in vitro revealed that aromatic‐turmerone targeted Toll‐like receptor 4 mediated downstream signaling, and lowered the release of inflammatory mediators. Conclusion : These observations indicate that aromatic‐turmerone is effective in preventing brain damage caused by neuroinflammation and may be useful in the treatment of neuronal inflammatory diseases.     

High‐fat meal induced postprandial inflammation

Raised levels of circulating inflammatory markers are associated with coronary artery disease, obesity and type II diabetes. It has been proposed that the ingestion of high‐fat meals may serve as a stimulus to raise systemic inflammatory tone, although interventional studies have yielded conflicting results. We here review 57 studies of high‐fat meal induced acute postprandial inflammation to identify the most frequently reported markers of postprandial inflammation and to compare these results with the highly consistent low‐grade endotoxaemia model in man. Most plasma borne markers of inflammation, such as cytokines and soluble adhesion molecules, were not consistently raised after a high‐fat meal. However, pro‐inflammatory leukocyte surface markers, mRNA and proteins were elevated in almost all studies in which they were measured. These markers followed kinetics similar to those observed following intravenous injection of low doses of endotoxin in man, were positively associated with likelihood of contamination of test meals with pro‐inflammatory bacterial molecules and were reduced in several studies examining parallel meals supplemented with foodstuffs containing anti‐inflammatory phytochemicals. Future studies of postprandial inflammation may yield more consistent evidence by focusing on leukocyte, rather than plasma‐borne, markers of inflammation and by considering the test meal content of pro‐ and anti‐inflammatory dietary constituents.     

A novel mechanism underlying phytate‐mediated biological action‐phytate hydrolysates induce intracellular calcium signaling by a Gαq protein‐coupled receptor and phospholipase C‐dependent mechanism in colorectal cancer cells

Phytate (inositol hexa‐phosphate, IP6) possesses multiple biological functions including anticancer activity. IP6 is converted to inositol di‐, tri‐, and tetra‐phosphates (IP2, IP3, and IP4) by phytase in large intestinal microbes; however, their contribution to the IP6‐mediated functions has not been investigated. We have developed the preparations of IP2–4 and IP3‐rich phytate hydrolysate (IP3‐RPH) by IP6 digestion using microbial phytase, and examined the induction of intracellular Ca²⁺ signaling in response to the preparations in colorectal cancer cells. IP2–4, but not inositol (IP0) and IP6, induced increases in intracellular Ca²⁺ concentration ([Ca²⁺]_i) in Caco‐2 cells with the following rank order: IP3>IP2=IP4. Inositol tri‐phosphate (IP3)‐RPH induced increases in [Ca²⁺]_i in both undifferentiated Caco‐2 and HT‐29 cells, but not in differentiated Caco‐2. The IP3‐RPH‐induced [Ca²⁺]_i increase was resistant to extracellular Ca²⁺ depletion, however, it was impaired by inhibitors of phospholipase C, inositol 1, 4, 5 tri‐phosphate receptor, ryanodine receptor, and Gαq protein. These results show that the putative G protein‐coupled receptor on the plasma membrane senses the IP6 hydrolysates and activates phospholipase Cβ, resulting in Ca²⁺ mobilization through Ca²⁺ channels coupled with the inositol 1, 4, 5 tri‐phosphate and ryanodine receptors on the sarco‐endoplasmic reticulum Ca²⁺ store in colorectal cancer cells.     

The effects of green tea (–)‐epigallocatechin‐3‐gallate on reactive oxygen species in 3T3‐L1 preadipocytes and adipocytes depend on the glutathione and 67 kDa laminin receptor pathways

Green tea (–)‐epigallocatechin‐3‐gallate (EGCG) is known as to regulate obesity and fat cell activity. However, little information is known about the effects of EGCG on oxidative reactive oxygen species (ROS) of fat cells. Using 3T3‐L1 preadipocytes and adipocytes, we found that EGCG increased ROS production in dose‐ and time‐dependent manners. The concentration of EGCG that increased ROS levels by 180–500% was approximately 50 μM for a range of 8–16 h of treatment. In contrast, EGCG dose‐ and time‐dependently decreased the amount of intracellular glutathione (GSH) levels. EGCG was more effective than (–)‐epicatechin, (–)‐epicatechin‐3‐gallate, and (–)‐epigallocatechin in changing ROS and GSH levels. This suggests a catechin‐specific effect. To further examine the relation of GSH to ROS as altered by EGCG, we observed that exposure of preadipocytes and adipocytes to N‐acetyl‐L ‐cysteine (a GSH precursor) blocked the EGCG‐induced increases in ROS levels and decreases in GSH levels. These observations suggest a GSH‐dependent effect of EGCG on ROS production. While EGCG was demonstrated to alter levels of ROS and GSH, its signaling was altered by an EGCG receptor (the so‐called 67 kDa laminin receptor(67LR)) antiserum, but not by normal rabbit serum. These data suggest that EGCG mediates GSH and ROS levels via the 67LR pathway.