Dark Sweet Cherry (Prunus avium) Supplementation Reduced Blood Pressure and Pro-Inflammatory Interferon Gamma (IFNγ) in Obese Adults without Affecting Lipid Profile, Glucose Levels and Liver Enzymes.

Dark sweet cherries (DSC) are rich in fiber and polyphenols that decrease risk factors associated with obesity. This single-blind randomized placebo-controlled study investigated DSC effects on inflammation, cardiometabolic, and liver health biomarkers in obese adults. Participants (>18 years, body mass index (BMI) = 30-40 kg/m2) consumed 200 mL of DSC drink (juice supplemented with DSC powder) (n = 19) or a placebo drink (n = 21) twice/day for 30 days. Anthropometric and physiological biomarkers were monitored at baseline (D1), mid-point (D15), and endpoint (D30) visits. Blood inflammatory biomarkers were assessed at D1, D15, and D30, and blood lipids, glucose, and liver enzymes at D1 and D30. DSC consumption lowered systolic blood pressure (SBP) (p = 0.05) and decreased diastolic blood pressure (DBP) compared to placebo (p = 0.04). Stratification of participants by BMI revealed a greater (p = 0.008) SBP reduction in BMI > 35 participants. DSC lowered pro-inflammatory interferon-gamma (IFNγ) (p = 0.001), which correlated with SBP changes. The interleukin (IL)-1RA and SBP changes were correlated in the placebo group, as well as triglycerides (TG) with DBP. The increased IL-10 levels in the placebo group suggested a compensatory mechanism to counteract elevated IFNγ levels. No significant between-group differences were detected for blood lipids, glucose, and liver enzymes. In conclusion, DSC helped to decrease blood pressure levels and inflammation in obese adults.

The role of dietary polyphenols in osteosarcoma: A possible clue about the molecular mechanisms involved in a process that is just in its infancy.

Osteosarcoma (OS) is a primary malignant bone tumor mainly affecting children, teenagers and young adults, being associated with early metastasis and poor prognosis. The beneficial effects of polyphenols have been investigated in different areas, including their potential to fight OS. Polyphenols are believed to reduce morbidity and/or slow down the development of cancer. This review aimed to assess the effect of polyphenols in OS and investigate their molecular mechanisms. It was observed that the broad spectrum of health-promoting properties of plant polyphenols in OS occurs mainly due to modulation of reactive oxygen species, anti-inflammatory activity, anti-angiogenesis, apoptosis inducer, inhibition of invasion and metastasis. However, it is worth mentioning that although the promising effects of polyphenols in the fight against OS, most of the studies have been performed using in vitro and in vivo animal models. Therefore, studies in humans are needed to validate the effectiveness of polyphenols in OS treatment. PRACTICAL APPLICATIONS: Polyphenols are widely used for various diseases, however, until now, their real role in the treatment of osteosarcoma remains unknown. This review provides a broad spectrum of research conducted with polyphenols and their potential as adjuvant therapy in the treatment of osteosarcoma. However, prior to their clinical application for osteosarcoma treatment, there is a need to isolate and identify specific polyphenolic compounds with high antitumor activity, increase their oral bioavailability, and to investigate their interactions with chemotherapeutic drugs being used in clinical practice.

Jaboticaba (Myrciaria cauliflora) Peel Supplementation Prevents Hepatic Steatosis Through Hypolipidemic Effects and Cholesterol Metabolism Modulation in Diet-Induced Nonalcoholic Fatty Liver Disease Rat Model.

Jaboticaba (Myrciaria cauliflora), a Brazilian fruit, is a good source of dietary fiber and phenolic compounds, which are concentrated mainly in the peel. These compounds have been considered promising in prevention and treatment of hypercholesterolemia and hepatic steatosis. In this study, we investigated the effects of 4% jaboticaba peel powder (JPP) supplementation on cholesterol metabolism and hepatic steatosis in livers of rats fed a high-fat (HF) diet. The rats were fed a standard AIN-93M (control) diet or an HF diet containing 32% lard and 1% cholesterol, both with and without 4% JPP. The M. cauliflora peel composition revealed a low-lipid high-fiber content and phenolic compounds. The phenolic compounds in JPP, tentatively identified by high-performance liquid chromatography and mass spectrometry (HPLC-MS/MS) analysis, were confirmed to contain phenolic acids, flavonoids, and anthocyanins. Moreover, JPP presented significant antioxidant activity in vitro and was not cytotoxic to HepG2 cells, as determined by the lactate dehydrogenase (LDH) assay. After 6 weeks of treatment, our results showed that JPP supplementation increased lipid excretion in feces, reduced serum levels of total cholesterol and nonhigh-density lipoprotein cholesterol, decreased serum aspartate aminotransferase (AST) activity, and attenuated hepatic steatosis severity in rats fed the HF diet. Furthermore, JPP treatment downregulated expression of ACAT-1, LXR-α, CYP7A1, and ABCG5 genes. Therefore, jaboticaba peel may represent a viable dietary strategy to prevent nonalcoholic fatty liver disease as the JPP treatment alleviated hepatic steatosis through improvement of serum lipid profiles and modulation of mRNA expression of genes involved in cholesterol metabolism.

Dark Sweet Cherry (Prunus avium) Phenolics Enriched in Anthocyanins Induced Apoptosis in MDA-MB-453 Breast Cancer Cells through MAPK-Dependent Signaling and Reduced Invasion via Akt and PLCγ-1 Downregulation.

Dark sweet cherries (DSCs) are rich source of phenolics known to exert anticancer and anti-invasive activities. This study elucidated the molecular mechanisms underlying the activity of DSC phenolics against MDA-MB-453 breast cancer cells In Vitro. Cells were treated with DSC phenolics in whole extract (WE), and fractions enriched in anthocyanins (ACN) and proanthocyanidins (PCN) at concentrations that inhibited cell growth by 50%. Results showed that DSC phenolics suppressed Akt and PLCγ-1 activation, and inhibited cell motility and invasion, but only ACN reached significance. The extrinsic and intrinsic apoptotic pathways were also activated by DSC phenolics via caspase-8 cleavage and increased Bax/Bcl-2 ratio, with ACN exhibiting significant activation and stronger PARP-1 cleavage. Furthermore, sustained activation of mitogen-activated protein kinases (MAPKs) ERK1/2 and p38 was observed wherein ERK1/2 (U0126) and p38 (SB203580) inhibitors confirmed crosstalk ERK1/2-Akt and MAPK intrinsic mitochondrial pathways. In conclusion, DSC phenolics inhibited MDA-MB-453 breast cancer cells by targeting cell signaling pathways that induce apoptosis and suppress cell invasion, with ACN showing enhanced chemopreventive activities.

The Impact of Mushroom Polysaccharides on Gut Microbiota and Its Beneficial Effects to Host: A Review.

Mushroom polysaccharides are a type of bioactive macromolecular which isolated from fruiting bodies, mycelia or fermentation broths of edible or medicinal fungus. Recently, mushroom polysaccharides have attracted a lot of attention for regulating gut microbiota via reducing the levels of pathogens and stimulating the growth of beneficial microorganisms, thus creating new possibilities for their use in nutraceutical and functional foods industries. The current review summarizes the isolation, purification and structural characterization methods of mushroom polysaccharides, the degradation of mushroom polysaccharides in intestine, the impacts of mushroom polysaccharides on gut microbiota community and short chain fatty acids (SCFAs) productivity, and the beneficial effects of mushroom polysaccharides to host by targeting gut microbiota. We hope this article can offer some theoretical bases and inspirations for the mechanism study of the bioactivity of mushroom polysaccharides.

Quinoa intake reduces plasma and liver cholesterol, lessens obesity-associated inflammation, and helps to prevent hepatic steatosis in obese db/db mouse.

The purpose of this study was to investigate if quinoa (Chenopodium quinoa Willd.), a good source of nutrients, fibre, and phytochemicals, can modulate risk disease biomarkers on obese-diabetic (db/db) mice. The db/db mice fed quinoa-supplemented (quinoa) or AIN-93G diet (obese) were compared to lean control fed AIN-93G diet. Quinoa intake reduced at significant level plasma total-cholesterol (total-c), LDL-c, and oxidized-LDL to levels similar to lean; lessened protein carbonyls and interleukin (IL)-6. The hepatic steatosis and total-c accumulation in liver were also similar between lean and quinoa and lower than obese. Quinoa fibre and phytochemicals may have contributed to these health benefits. However, quinoa intake increased plasma insulin and did not protect from other pathophysiological manifestations of the db/db research model. More studies are needed with other research models and quinoa doses achievable by human diet to validate the clinical relevance of this study.

Non-anthocyanin phenolics in cherry (Prunus avium L.) modulate IL-6, liver lipids and expression of PPARδ and LXRs in obese diabetic (db/db) mice.

Anthocyanin-rich cherries are known for preventing/decreasing risk factors associated with obesity; however, the specific benefits exerted by cherry non-anthocyanin phenolics are not clear. Obese diabetic (db/db) mice fed a diet supplemented with anthocyanin-depleted cherry powder (cherry) were compared to db/db (obese) or lean counterparts (lean) fed a control isocaloric diet for 12 weeks. The reduced plasma interleukin (IL)-6 and improved liver health may be mediated by cherry fibre and non-anthocyanin phenolics. Benefits for liver health included reduction of lipids and protein carbonyls, and modulation of peroxisome proliferator-activated receptor (PPAR)δ mRNA to resemble levels in lean. Lack of plasma antilipidemic, improvement of antioxidant defenses, and PPARα/γ mRNA modulation in liver suggest cherry anthocyanins specific benefits. This is the first study to elucidate in vivo the potential benefits of cherry non-anthocyanin phenolics for diabetes-induced liver disorders and the importance of choosing processing technologies that preserve anthocyanins and health benefits of whole cherries.

Effect of dark sweet cherry powder consumption on the gut microbiota, short-chain fatty acids, and biomarkers of gut health in obese db/db mice.

Cherries are fruits containing fiber and bioactive compounds (e.g., polyphenolics) with the potential of helping patients with diabetes and weight disorders, a phenomenon likely related to changes in the complex host-microbiota milieu. The objective of this study was to investigate the effect of cherry supplementation on the gut bacterial composition, concentrations of caecal short-chain fatty acids (SCFAs) and biomarkers of gut health using an in vivo model of obesity. Obese diabetic (db/db) mice received a supplemented diet with 10% cherry powder (supplemented mice, n = 12) for 12 weeks; obese (n = 10) and lean (n = 10) mice served as controls and received a standard diet without cherry. High-throughput sequencing of the 16S rRNA gene and quantitative real-time PCR (qPCR) were used to analyze the gut microbiota; SCFAs and biomarkers of gut health were also measured using standard techniques. According to 16S sequencing, supplemented mice harbored a distinct colonic microbiota characterized by a higher abundance of mucin-degraders (i.e., Akkermansia) and fiber-degraders (the S24-7 family) as well as lower abundances of Lactobacillus and Enterobacteriaceae. Overall this particular cherry-associated colonic microbiota did not resemble the microbiota in obese or lean controls based on the analysis of weighted and unweighted UniFrac distance metrics. qPCR confirmed some of the results observed in sequencing, thus supporting the notion that cherry supplementation can change the colonic microbiota. Moreover, the SCFAs detected in supplemented mice (caproate, methyl butyrate, propionate, acetate and valerate) exceeded those concentrations detected in obese and lean controls except for butyrate. Despite the changes in microbial composition and SCFAs, most of the assessed biomarkers of inflammation, oxidative stress, and intestinal health in colon tissues and mucosal cells were similar in all obese mice with and without supplementation. This paper shows that dietary supplementation with cherry powder for 12 weeks affects the microbiota and the concentrations of SCFAs in the lower intestinal tract of obese db/db diabetic mice. These effects occurred in absence of differences in most biomarkers of inflammation and other parameters of gut health. Our study prompts more research into the potential clinical implications of cherry consumption as a dietary supplement in diabetic and obese human patients.

Red raspberry (Rubus idaeus L.) intake decreases oxidative stress in obese diabetic (db/db) mice.

Red raspberry fruit intake was investigated on obese diabetic (db/db) mice for 8weeks. Animals fed isocaloric diets (5.3% freeze-dried raspberry, or control) were assessed for obesity-diabetes-disease risk biomarkers. Results showed that raspberry intake improved antioxidant status and lessened plasma interleukin (IL)-6 (0.3-fold of control, p<0.1); most likely through enhancing glutathione peroxidase (GPx) activity in liver (4.3-fold of control), and in blood (2.1-fold of control). Other disease-risk biomarkers were similar between groups (p>0.05). Plasma levels of total cholesterol (T-CHL), low density lipoprotein-cholesterol (LDL-CHL), and resistin were higher in the raspberry group. Overall, the enhanced detoxifying cell defenses exerted by raspberry intake might be due to its polyphenolics and fibre. This study demonstrates in vivo that raspberry intake, at a dose that can be achieved by human consumption, might protect against diabetes-induced oxidative stress.

Polyphenolic extracts from cowpea (Vigna unguiculata) protect colonic myofibroblasts (CCD18Co cells) from lipopolysaccharide (LPS)-induced inflammation--modulation of microRNA 126.

Cowpea (Vigna unguiculata) is a drought tolerant crop with several agronomic advantages over other legumes. This study evaluated varieties from four major cowpea phenotypes (black, red, light brown and white) containing different phenolic profiles for their anti-inflammatory property on non-malignant colonic myofibroblasts (CCD18Co) cells challenged with an endotoxin (lipopolysaccharide, LPS). Intracellular reactive oxygen species (ROS) assay on the LPS-stimulated cells revealed antioxidative potential of black and red cowpea varieties. Real-time qRT-PCR analysis in LPS-stimulated cells revealed down-regulation of proinflammatory cytokines (IL-8, TNF-α, VCAM-1), transcription factor NF-κB and modulation of microRNA-126 (specific post-transcriptional regulator of VCAM-1) by cowpea polyphenolics. The ability of cowpea polyphenols to modulate miR-126 signaling and its target gene VCAM-1 were studied in LPS-stimulated endothelial cells transfected with a specific inhibitor of miR-126, and treated with 10 mg GAE/L black cowpea extract where the extract in part reversed the effect of the miR-126 inhibitor. This suggests that cowpea may exert their anti-inflammatory activities at least in part through induction of miR-126 that then down-regulate VCAM-1 mRNA and protein expressions. Overall, Cowpea therefore is promising as an anti-inflammatory dietary component.

Carbohydrate-Free Peach (Prunus persica) and Plum (Prunus salicina) [corrected] Juice Affects Fecal Microbial Ecology in an Obese Animal Model.

BACKGROUND: Growing evidence shows the potential of nutritional interventions to treat obesity but most investigations have utilized non-digestible carbohydrates only. Peach and plum contain high amounts of polyphenols, compounds with demonstrated anti-obesity effects. The underlying process of successfully treating obesity using polyphenols may involve an alteration of the intestinal microbiota. However, this phenomenon is not well understood. METHODOLOGY/PRINCIPAL FINDINGS: Obese Zucker rats were assigned to three groups (peach, plum, and control, n = 10 each), wild-type group was named lean (n = 10). Carbohydrates in the fruit juices were eliminated using enzymatic hydrolysis. Fecal samples were obtained after 11 weeks of fruit or control juice administration. Real-time PCR and 454-pyrosequencing were used to evaluate changes in fecal microbiota. Over 1,500 different Operational Taxonomic Units at 97% similarity were detected in all rats. Several bacterial groups (e.g. Lactobacillus and members of Ruminococcacea) were found to be more abundant in the peach but especially in the plum group (plum juice contained 3 times more total polyphenolics compared to peach juice). Principal coordinate analysis based on Unifrac-based unweighted distance matrices revealed a distinct separation between the microbiota of control and treatment groups. These changes in fecal microbiota occurred simultaneously with differences in fecal short-chain acids concentrations between the control and treatment groups as well as a significant decrease in body weight in the plum group. CONCLUSIONS: This study suggests that consumption of carbohydrate-free peach and plum juice has the potential to modify fecal microbial ecology in an obese animal model. The separate contribution of polyphenols and non-polyphenols compounds (vitamins and minerals) to the observed changes is unknown.

Assessing non-digestible compounds in apple cultivars and their potential as modulators of obese faecal microbiota in vitro.

The health benefits of apple bioactive compounds have been extensively reported. However, only few studies have focused on bioactive compounds that are not absorbed and metabolised during gastrointestinal digestion and can induce changes in microbial populations of faeces. We have characterised Braeburn, Fuji, Gala, Golden Delicious, Granny Smith, McIntosh and Red Delicious cultivars and found significant differences for extractable phenolics (1.08-9.2mg/g) non-extractable proanthocyanidins (3.28-5.7mg/g), and dietary fibre (20.6-32.2%) among cultivars with Granny Smith having the highest contents. Granny Smith was used after in vitro digestion for fermentation of faeces from diet-induced obese mice. Results showed that relative abundances of Firmicutes, Bacteroidetes, Enterococcus, Enterobacteriaceae, Escherichia coli, and Bifidobacterium in apple cultured faeces tended to resemble the abundance in faeces from lean mice with increased trend in the production of butyric acid. These results suggest that apple non-digestible compounds might help to re-establish a disturbed microbiota balance in obesity.

Technical note: optimization of lactose quantification based on coupled enzymatic reactions.

A colorimetric microplate-adapted lactose assay was developed to quantify lactose in dairy products. The assay was based on the coupled enzymatic reaction of ß-galactosidase-glucose oxidase-horseradish peroxidase using Amplex red as detection probe. The assay showed good linearity in the range of 0.1 to 0.5mmol of lactose/L, with a limit of detection of 0.0433mmol/L and a limit of quantification of 0.1313mmol/L. The lactose assay at optimized conditions (5 U of ß-galactosidase/mL, 5 U of glucose oxidase/mL, 1 U of horseradish peroxidase/mL, and 100µmol of Amplex red/L for 1h at 37°C in the dark) showed good correlation with a commercial lactose enzymatic kit with intraassay variation below 10% and interassay variations below 7.6%. The developed lactose microplate assay can be adopted as routine analysis for lactose determination in dairy products due to its relatively low cost compared with a commercial kit, relatively short reaction time, and high sensitivity and reproducibility.

The drug resistance suppression induced by curcuminoids in colon cancer SW-480 cells is mediated by reactive oxygen species-induced disruption of the microRNA-27a-ZBTB10-Sp axis.

SCOPE: Mechanisms involving the curcuminoids effects in decreasing the prooncogenic specificity protein (Sp) transcription factors, and Sp-regulated genes in SW-480 colon cancer cells and how the multidrug resistance protein (MDR1) inhibition is mediated by Sp suppression. METHODS AND RESULTS: HT-29 and SW-480 colon cancer and normal CCD-18Co colon fibroblast cells were treated with curcuminoids previously analyzed by HPLC. Gene and protein expression regulation were assessed by RT-PCR, transfections with expression constructs, and Western blots. Curcuminoids (2.5-10 µg/mL) suppressed preferentially the growth of SW-480 and HT-29 compared to CCD-18Co cells and enhanced the anticancer activity of the chemotherapeutic drug 5-fluorouracil due to the suppression of MDR1. Additionally, Sp1, Sp3, and Sp4 and Sp-regulated genes were downregulated by curcuminoids in SW-480 and this was accompanied by suppression of microRNA-27a (miR-27a) and induction of ZBTB10, an mRNA target of miR-27a and a transcriptional repressor of Sp expression. This mechanism was mediated by the induction of ROS. RNA-interference and transfection with ZBTB10-expression plasmid demonstrated that MDR1 was regulated by Sp1 and Sp3 and the disruption of the miR-27a-ZBTB10-Sp axis. CONCLUSION: Colon cancer treatment with curcuminoids will enhance the therapeutic effects of drugs in patients who have developed drug resistance.

Micropropagation effect on the anti-carcinogenic activitiy of polyphenolics from Mexican oregano (Poliomintha glabrescens Gray) in human colon cancer cells HT-29.

Phenolic extracts obtained from spices are known to have anti-carcinogenic activities but little is known about the effect of micropropagation on these beneficial effects. The main objective of this study was to evaluate the cytotoxic activity of flavonoid-enriched extracts (FEE) from the leaves of wild (WT), in vitro (IN), and ex vitro (EX) grown oregano plants in colon cancer cells HT-29 and the non-cancer cells CCD-18Co. Cell proliferation of HT-29 cells was reduced to 50 % by WT, IN, and EX at concentrations of 4.01, 1.32, and 4.84 mg of gallic acid equivalents (GAE)/L, respectively. In contrast, in CCD-18Co cells, higher concentrations were required for the same cytotoxic effect. At 6 mg GAE/L, WT and IN reduced the production of reactive oxygen species (ROS) of lipopolysaccharides (LPS)-stimulated control cells to 59.89 and 59.43 %, respectively, and EX to 73.89 %. The mRNA of Caspase-3 was increased 1.53-fold when cells were treated with 4 mg GAE/L of IN extract, and tumor necrosis factor receptor superfamily, member 6 (FAS), and BCL2-associated X protein (BAX) mRNA increased 2.55 and 1.53 fold, respectively. Results on protein expression corroborated the apoptotic effects with a significant decrease of B-cell lymphoma 2 (BCL2) expression for all treatments but more remarkable for EX that also showed the most intense signal of BAX. Overall, FEE extracts derived from micropropagation had increased pro-apoptotic effects, however extracts from the in vitro plants produced more efficacy at the transcriptional level while extracts from the ex vitro plant were superior at the traductional level.

Betulinic acid decreases ER-negative breast cancer cell growth in vitro and in vivo: role of Sp transcription factors and microRNA-27a:ZBTB10.

Betulinic acid (BA), a pentacyclic triterpenoid isolated from tree bark is cytotoxic to cancer cells. There is evidence that specificity proteins (Sps), such as Sp1, Sp3, and Sp4, are overexpressed in tumors and contribute to the proliferative and angiogenic phenotype associated with cancer cells. The objective of this study was to determine the efficacy of BA in decreasing the Sps expression and underlying mechanisms. Results show that BA decreased proliferation and induced apoptosis of estrogen-receptor-negative breast cancer MDA-MB-231 cells. The BA-induced Sp1, Sp3, and Sp4 downregulation was accompanied by increased zinc finger ZBTB10 expression, a putative Sp-repressor and decreased microRNA-27a levels, a microRNA involved in the regulation of ZBTB10. Similar results were observed in MDA-MB-231 cells transfected with ZBTB10 expression plasmid. BA induced cell cycle arrest in the G2/M phase and increased Myt-1 mRNA (a microRNA-27a target gene), which causes inhibition in G2/M by phosphorylation of cdc2. The effects of BA were reversed by transient transfection with a mimic of microRNA-27a. In nude mice with xenografted MDA-MB-231 cells, tumor size and weight were significantly decreased by BA treatment. In tumor tissue, ZBTB10 mRNA was increased while mRNA and protein of Sp1, Sp3 and Sp4, as well as mRNA of vascular endothelial growth factor receptor (VEGFR), survivin and microRNA-27a were decreased by BA. In lungs of xenografted mice, human ß2-microglobulin mRNA was decreased in BA-treated animals. These results show that the anticancer effects of BA are at least in part based on interactions with the microRNA-27a-ZBTB10-Sp-axis causing increased cell death.

Polyphenolics from açaí ( Euterpe oleracea Mart.) and red muscadine grape (Vitis rotundifolia ) protect human umbilical vascular Endothelial cells (HUVEC) from glucose- and lipopolysaccharide (LPS)-induced inflammation and target microRNA-126.

Endothelial anti-inflammatory effects of açaí (Ac) and red muscadine grape (Gp) polyphenolics have not been extensively investigated. It was hypothesized that polyphenolics from Ac and Gp exert comparable protective effects in human vascular endothelial cells (HUVEC) upon inflammatory stress. Furthermore, this study investigated whether microRNAs relevant to endothelial function might be regulated by Ac and Gp. Results showed that Ac and Gp (5-20 mg gallic acid equivalent/L) protected HUVEC against glucose-induced oxidative stress and inflammation. Glucose-induced expression of interleukin-6 and -8 was down-regulated by Ac and Gp at mRNA and protein levels. Upon lipopolysaccharide (LPS; 1 µg/L)-induced inflammation, Ac and Gp inhibited gene expression of adhesion molecules and NF-κB activation to similar extents, although Gp was more effective in decreasing PECAM-1 and ICAM-1 protein. Of the screened microRNAs, only microRNA-126 expression was found to be modulated by Ac and Gp as the underlying mechanism to inhibit gene and protein expression of VCAM-1.

Flavonol-rich fractions of yaupon holly leaves (Ilex vomitoria, Aquifoliaceae) induce microRNA-146a and have anti-inflammatory and chemopreventive effects in intestinal myofibroblast CCD-18Co cells.

Polyphenolics extracted from yaupon holly (Ilex vomitoria, Aquifoliaceae) (YH) leaves were investigated in human colon cells for their chemopreventive and anti-inflammatory activities. An activity-guided fractionation allowed the selection of YH flavonol-rich fraction due to its preferential inhibition of HT-29 colon cancer viability over the normal CCD-18Co colon cells. Quercetin and kaempferol 3-rutinosides, main components identified in this fraction, protected CCD-18Co cells against reactive oxidative species (ROS) in part due to increased activity of antioxidant enzymes. In addition, up-regulation of microRNA-146a (miR-146a) known as a negative regulator of pro-inflammatory NF-κB activation was the underlying molecular mechanism that protected CCD-18Co from inflammation.

Anticarcinogenic effects of polyphenolics from mango (Mangifera indica) varieties.

Many polyphenolics contained in mango have shown anticancer activity. The objective of this study was to compare the anticancer properties of polyphenolic extracts from several mango varieties (Francis, Kent, Ataulfo, Tommy Atkins, and Haden) in cancer cell lines, including Molt-4 leukemia, A-549 lung, MDA-MB-231 breast, LnCap prostate, and SW-480 colon cancer cells and the noncancer colon cell line CCD-18Co. Cell lines were incubated with Ataulfo and Haden extracts, selected on the basis of their superior antioxidant capacity compared to the other varieties, where SW-480 and MOLT-4 were statistically equally most sensitive to both cultivars followed by MDA-MB-231, A-549, and LnCap in order of decreasing efficacy as determined by cell counting. The efficacy of extracts from all mango varieties in the inhibition of cell growth was tested in SW-480 colon carcinoma cells, where Ataulfo and Haden demonstrated superior efficacy, followed by Kent, Francis, and Tommy Atkins. At 5 mg of GAE/L, Ataulfo inhibited the growth of colon SW-480 cancer cells by approximately 72% while the growth of noncancer colonic myofibroblast CCD-18Co cells was not inhibited. The growth inhibition exerted by Ataulfo and Haden polyphenolics in SW-480 was associated with an increased mRNA expression of pro-apoptotic biomarkers and cell cycle regulators, cell cycle arrest, and a decrease in the generation of reactive oxygen species. Overall, polyphenolics from several mango varieties exerted anticancer effects, where compounds from Haden and Ataulfo mango varieties possessed superior chemopreventive activity.