FASN promotes anoikis resistance in colorectal liver metastases through the ERK1/2 pathway.

PURPOSE: Colorectal cancer (CRC) is recognized as the third most common form of malignancy, with the liver frequently serving as the main site for metastasis. Anoikis resistance (AR) is critical in colorectal cancer liver metastases (CRLM). Fatty acid synthase (FASN), essential in lipid synthesis, mediates AR in many cancers. The present research examines the function of FASN in ERK1/2-mediated AR in CRLM and evaluates its therapeutic potential. METHODS: We performed scratch and migration experiment to evaluate the migration capacity of the LoVo cells. Flow cytometry was employed to identify cell apoptosis. The levels of FASN, p-ERK1/2, and proteins related to apoptosis was analyzed by Western blot. The mRNA level of FASN was determined by q-PCR after FASN silencing. In addition, we used an intrasplenic liver metastasis model of nude to assess the effect of FASN on CRLM. RESULTS: In vitro experiments showed that after FASN silencing, the cell apoptosis rate was increased, migration capability was notably decreased, the expression of p-ERK1/2, the proteins related to anti-apoptotic were significantly decreased, and the proteins related to apoptosis were significantly increased. In vivo experiments showed that AR significantly increased the number of liver metastatic foci, whereas FASN silencing significantly inhibited CRLM. CONCLUSION: These results suggest that FASN silencing suppressed AR through the ERK 1/2 pathway, which in turn suppressed CRLM.

A review of extraction, purification, structural properties and biological activities of legumes polysaccharides.

In recent years, polysaccharides derived from legumes polysaccharides have aroused worldwide interests. Phytochemical and pharmacological studies have studied the physicochemical properties (emulsification, stability and foaming) and demonstrated the biological activities (immune regulation, anti-oxidation, anti-tumor, hypoglycemic, hypolipidemic and intestinal flora regulation) of legumes polysaccharides. Besides, it is reported that the extraction methods will affect the structural features of polysaccharides, thus further changing their physicochemical properties and biological activities. This review appraised the available literatures described the extraction, purification, structural characterization, biological activity and functional properties of legumes polysaccharides in recent years. It can provide useful research underpinnings and updated information for the development and application of related polysaccharides in functional food and medicinal field.

Structural Elucidation and Antioxidant Activities of a Neutral Polysaccharide From Arecanut (Areca catechu L.).

A novel neutral polysaccharide designated as PAP1b was isolated from Areca catechu L. by hot water extraction, ethanol precipitation, and column chromatography. PAP1b was mainly composed of mannose, galactose, xylose, and arabinose in a ratio of 4.1:3.3:0.9:1.7, with an average molecular weight of 37.3 kDa. Structural characterization indicated that the backbone of PAP1b appeared to be composed mainly of → 6-ß-Manp-(1 →, → 4)-α-Galp-(1 → and → 3,6)-ß-Manp-(1 →) residues with some branches, and terminal of (1 →)-linked-ß-Manp residues. The results of bioactivity experiments showed that PAP1b had antioxidant in vitro, esspecially on scavenging DPPH and hydroxyl radicals. Therefore, the polysaccharide from Areca catechu L. could be used as a potential antioxidant in functional food.

Metagenomic analysis of gut microbiota modulatory effects of jujube (Ziziphus jujuba Mill.) polysaccharides in a colorectal cancer mouse model.

Accumulating evidence has reported that the gut microbiota could play important roles in the occurrence and progression of colorectal cancer. The nondigestible plant polysaccharides have always been fermented by the intestinal microbiota. Polysaccharides, the predominant functional composition found in jujube fruit, has been shown to inhibit carcinogenesis in animal models. However, the molecular mechanisms involved in polysaccharides preventing carcinogenesis are still uncharacterized. The aim of this study was to investigate the modulatory effects of jujube polysaccharides (JP) on intestinal microbiota, and the influence of JP on the gut flora structure was then analyzed using an AOM/DSS-induced colitis cancer mouse model, using high-throughput sequencing. Contrasted with control group, the addition of JP could ward off colon cancer by ameliorating colitis cancer-induced gut dysbiosis. In addition, there was a significant decrease in Firmicutes/Bacteroidetes post JP treatment. What's more, KEGG pathways of metabolic pathways, ATP-binding cassette (ABC) transporters and two-component system enriched the most differentially expressed genes after JP intervention for 13 weeks. These results suggested that JP showed prebiotic-like activities by positively modulating intestinal microbiota and affecting certain metabolic pathways contributing to host health. In conclusion, our results demonstrated an appreciable capability of JP to restore the gut microbiota profile altered by AOM/DSS, indicating the potential of jujube polysaccharides as promising prebiotic candidates for the prevention and treatment of colorectal cancer.

Physicochemical properties, structures, bioactivities and future prospective for polysaccharides from Plantago L. (Plantaginaceae): A review.

Since ancient times, the herbal plant, Plantago L. (Plantaginaceae) has been proposed to have medicinal and food benefits. Recent pharmacological and phytochemical studies have shown that polysaccharides derived from Plantago L. exert multiple medicinal and nutritional benefits, including immunomodulatory, antioxidant, hypoglycemic, hypolipidemic activities, antitumor, and gastrointestinal-protective effects. These health and pharmacological benefits are of great interest to the public, academia and biotechnology industries. This paper provides an overview of recent advances in the physiochemical, structural features and biological effects of polysaccharides derived from Plantago L. This comprehensive review also covers recent advances in the field and outlines future research and applications of these polysaccharides.

Isolation, Structures, and Bioactivities of the Polysaccharides from Gynostemma pentaphyllum (Thunb.) Makino: A Review.

Polysaccharides obtained from Gynostemma pentaphyllum (Thunb.) Makino have promising prospects in functional food and nutraceuticals due to its broad range of biological activities including antioxidant, immunomodulatory, antitumor, hepatoprotective, neuroprotective, and antifatigue activities. These beneficial biological activities are related to chemical composition and structure of the G. pentaphyllum polysaccharides. The molecular weight, monosaccharide composition, and chemical structures could be influenced by both different extraction/purification techniques employed to obtain polysaccharide enriched products. The purpose of this article is to review previous and current literature regarding the extraction, purification, structural characterization, and biological activity of G. pentaphyllum polysaccharides. This review provides a useful bibliography for the further investigation, production, and application of G. pentaphyllum polysaccharides as functional foods and nutraceuticals.

Quercetin and quercetin-3-O-glucuronide are equally effective in ameliorating endothelial insulin resistance through inhibition of reactive oxygen species-associated inflammation.

SCOPE: Quercetin represents antioxidative/antiinflammatory flavonoids widely distributed in the human diet. Quercetin is efficiently metabolized during absorption to quercetin-3-O-glucuronide. This study aims to parallelly investigate whether quercetin and quercetin-3-O-glucuronide exert protection against palmitate (PA)-induced inflammation and insulin resistance in the endothelium. METHODS AND RESULTS: Human umbilical vein endothelial cells were pretreated with quercetin and quercetin-3-O-glucuronide for 30 min, and then incubated with 100 µM PA for 30 min or 12 h with or without insulin. PA stimulation led to reactive oxygen species (ROS) production with collapse of mitochondrial membrane potential (Δψm). Quercetin and quercetin-3-O-glucuronide inhibited ROS overproduction and effectively restored Δψm, demonstrating their chemorpotection of mitochondrial function through antioxidative actions. Also, quercetin and quercetin-3-O-glucuronide inhibited ROS-associated inflammation by inhibition of interleukin-6 and tumor necrosis factor-α production with suppression of IKKß/NF-κB phosphorylation. Inflammation impaired insulin PI3K signaling and reduced insulin-mediated nitric oxide (NO) production. Quercetin and quercetin-3-O-glucuronide facilitated PI3K signaling by positive regulation of serine/tyrosine phosphorylation of insulin receptor substrate-1 (IRS-1) and restoration of downstream Akt/eNOS activation, leading to an increased insulin-mediated NO level. CONCLUSION: The above-mentioned evidence indicates that quercetin and quercetin-3-O-glucuronide are equally effective in inhibiting ROS-associated inflammation and ameliorating insulin resistant endothelial dysfunction by beneficial regulation of IRS-1 function.

Opposite effects of quercetin, luteolin, and epigallocatechin gallate on insulin sensitivity under normal and inflammatory conditions in mice.

Flavonoids are polyphenolic compounds ubiquitous in plants. Quercetin, luteolin, and epigallocatechin gallate (EGCG) are flavonoids with a number of biochemical and cellular actions relevant to glucose homeostasis, but their regulation of insulin action is still uncertain. This study aims to evaluate the regulation of insulin action by quercetin, luteolin, and EGCG under normal and inflammatory conditions in mice. Oral administration of quercetin, luteolin, and EGCG impaired glucose tolerance and blunted the effect of insulin to low blood glucose. Luteolin and EGCG, but not quercetin, inhibited glucose load-induced insulin receptor substrate-1(IRS-1) tyrosine and Akt phosphorylation in adipose tissue. Meanwhile, insulin-stimulated glucose uptake was also inhibited by these flavonoids. We induced insulin resistance in mice by treatment with activated macrophages-derived conditioned medium (Mac-CM) and observed that quercetin, luteolin, and EGCG reversed glucose intolerance with improving insulin sensitivity. Quercetin, luteolin, and EGCG inhibited inflammation-evoked IKKß activation and IRS-1 serine phosphorylation in adipose tissue, and thereby effectively restored glucose load-stimulated IRS-1 tyrosine and Akt phosphorylation, leading to an increase in insulin-mediated glucose uptake in adipocytes. The aforementioned results showed opposite effects of quercetin, luteolin, and EGCG on insulin sensitivity in mice. The different modulation of IRS-1 function by phosphorylating modification under normal and inflammatory conditions should be a key controlling for their action in regulation of insulin sensitivity.

Positive and negative regulation of insulin action by genistein in the endothelium.

Genistein is an isoflavone phytoestrogen with biological activities in management of metabolic disorders. This study aims to evaluate the regulation of insulin action by genistein in the endothelium. Genistein inhibited insulin-stimulated tyrosine phosphorylation of insulin receptor substrate-1 (IRS-1) and attenuated downstream Akt and endothelial nitric oxide synthase (eNOS) phosphorylation, leading to a decreased nitric oxide (NO) production in endothelial cells. These results demonstrated its negative regulation of insulin action in the endothelium. Palmitate (PA) stimulation evoked inflammation and induced insulin resistance in endothelial cells. Genistein inhibited IKKß and nuclear factor-кB (NF-кB) activation with down-regulation of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) production and expression. Genistein inhibited inflammation-stimulated IRS-1 serine phosphorylation and restored insulin-mediated tyrosine phosphorylation. Genistein restored insulin-mediated Akt and eNOS phosphorylation, and then led to an increased NO production from endothelial cells, well demonstrating its positive regulation of insulin action under insulin-resistant conditions. Meanwhile, genistein effectively inhibited inflammation-enhanced mitogenic actions of insulin by down-regulation of endothelin-1 and vascular cell adhesion protein-1 overexpression. PA stimulation impaired insulin-mediated vessel dilation in rat aorta, while genistein effectively restored the lost vasodilation in a concentration-dependent manner (0.1, 1 and 10 µM). These results suggested that genistein inhibited inflammation and ameliorated endothelial dysfunction implicated in insulin resistance. Better understanding of genistein action in regulation of insulin sensitivity in the endothelium could be beneficial for its possible applications in controlling endothelial dysfunction associated with diabetes and insulin resistance.