Metabolism and Anticancer Mechanisms of Selocompounds: Comprehensive Review.

Selenium (Se) is an essential micronutrient with several functions in cellular and molecular anticancer processes. There is evidence that Se depending on its chemical form and the dosage use could act as a modulator in some anticancer mechanisms. However, the metabolism of organic and inorganic forms of dietary selenium converges on the main pathways. Different selenocompounds have been reported to have crucial roles as chemopreventive agents, such as antioxidant activity, activation of apoptotic pathways, selective cytotoxicity, antiangiogenic effect, and cell cycle modulation. Nowadays, great interest has arisen to find therapies that could enhance the antitumor effects of different Se sources. Herein, different studies are reported related to the effects of combinatorial therapies, where Se is used in combination with proteins, polysaccharides, chemotherapeutic agents or as nanoparticles. Another important factor is the presence of single nucleotide polymorphisms in genes related to Se metabolism or selenoprotein synthesis which could prevent cancer. These studies and mechanisms show promising results in cancer therapies. This review aims to compile studies that have demonstrated the anticancer effects of Se at molecular levels and its potential to be used as chemopreventive and in cancer treatment.

Effects of the substitution of wheat flour with raw or germinated ayocote bean (Phaseolus coccineus) flour on the nutritional properties and quality of bread.

This study aimed to evaluate the potential of 10%, 20%, and 30% of raw (ARF) and germinated (AGF) ayocote bean flour as a partial substitute for wheat flour in breadmaking. Substitution with both ayocote bean flours modified the water absorption and development time while maintaining the dough stability. Supplemented breads had 13%, 51%, and 132% higher protein, mineral, and crude fiber content, respectively, than control bread (100% wheat). The breadmaking features, color and crumb firmness, were affected by the substitution level. Sensory analysis revealed that germination could improve the taste and smell of breads produced with ayocote bean flour. The sensory attribute scores of 10% AGF bread were comparable to those of the control bread. Supplementation reduced the in vitro protein digestibility, although the effect was less pronounced in 10% ARF and 20% AGF breads. The limiting amino acid score of supplemented breads increased up to 70%, which improved their protein digestibility-corrected amino acid scores. Supplementation with 20% or 30% of both ARF and AGF increased resistant starch values and decreased the total digestible starch of breads. Thus, the results showed that substituting wheat with ARF or AGF improves the nutritional properties of bread. However, low substitution levels should be selected to avoid a considerable decrease in physical and sensory properties. PRACTICAL APPLICATION: Substituting wheat flour with ayocote bean flour improved the nutritional value of bread. Germination of ayocote beans decreased the cooking stability of composite dough. Bread fortified with ayocote flour had high levels of essential amino acids. Bread with raw or germinated ayocote flours had high limiting amino acid scores. Composite bread had high resistant starch and low total digestible starch.

Comparison of Regular and Selenium-Enriched Tortillas Produced from Sprouted Corn Kernels.

Corn kernels were soaked with different selenium (Se) solutions (0, 12 or 24 mg Na2SeO3/L), sprouted for different times and then lime-cooked for the pilot plant production of tortillas. The dough and tortillas were quantified in terms of total Se, starch and protein content. Also, in vitro digestibility, texture, color, and sensory properties were evaluated. Results indicated that lime-cooking times were significantly reduced from 39.15 to 14.34, 8.42 and 2.80 min when whole corn was compared with kernels germinated for 1, 2 or 3 days. The Se content of regular tortillas (0.08 µg/g dw) increased about eight-fold in tortillas (0.651-0.625 µg/g dw) produced of corn germinated for two day and treated with 24 mg of Na2SeO3/L. The highest α-amylase activity and lower starch viscosity values were observed in 3-day germinated supplemented with the highest Se. Se-enriched tortillas produced from 2-day sprouted kernels treated with 12 mg Na2SeO3 showed the highest levels of general acceptability, texture and flavor.

Environmentally Friendly Methods for Flavonoid Extraction from Plant Material: Impact of Their Operating Conditions on Yield and Antioxidant Properties.

The flavonoids are compounds synthesized by plants, and they have properties such as antioxidant, anticancer, anti-inflammatory, and antibacterial, among others. One of the most important bioactive properties of flavonoids is their antioxidant effect. Synthetic antioxidants have side toxic effects whilst natural antioxidants, such as flavonoids from natural sources, have relatively low toxicity. Therefore, it is important to incorporate flavonoids derived from natural sources in several products such as foods, cosmetics, and drugs. For this reason, there is currently a need to extract flavonoids from plant resources. In this review are described the most important parameters involved in the extraction of flavonoids by unconventional methods such as ultrasound, pressurized liquid extraction, mechanochemical, high hydrostatic pressure, supercritical fluid, negative pressure cavitation, intensification of vaporization by decompression to the vacuum, microwave, infrared, pulsed electric field, high-voltage electrical discharges, and enzyme-assisted extraction. There are no unified operation conditions to achieve high yields and purity. Notwithstanding, progress has been achieved in the development of more advanced and environmentally friendly methods of extraction. Although in literature are found important advances, a complete understanding of the extraction process in each of the unconventional techniques is needed to determine the thermodynamic and kinetic mechanisms that govern each of the techniques.

Synergistic Combinations of Curcumin, Sulforaphane, and Dihydrocaffeic Acid against Human Colon Cancer Cells.

Nutraceutical combinations that act synergistically could be a powerful solution against colon cancer, which is the second deadliest malignancy worldwide. In this study, curcumin (C), sulforaphane (S), and dihydrocaffeic acid (D, a chlorogenic acid metabolite) were evaluated, individually and in different combinations, over the viability of HT-29 and Caco-2 colon cancer cells, and compared against healthy fetal human colon (FHC) cells. The cytotoxic concentrations to kill 50%, 75%, and 90% of the cells (CC50, CC75, and CC90) were obtained, using the MTS assay. Synergistic, additive, and antagonistic effects were determined by using the combination index (CI) method. The 1:1 combination of S and D exerted synergistic effects against HT-29 at 90% cytotoxicity level (doses 90:90 µM), whereas CD(1:4) was synergistic at all cytotoxicity levels (9:36-34:136 µM) and CD(9:2) at 90% (108:24 µM) against Caco-2 cells. SD(1:1) was significantly more cytotoxic for cancer cells than healthy cells, while CD(1:4) and CD(9:2) were similarly or more cytotoxic for healthy cells. Therefore, the SD(1:1) combination was chosen as the best. A model explaining SD(1:1) synergy is proposed. SD(1:1) can be used as a basis to develop advanced food products for the prevention/co-treatment of colon cancer.

Effect of Ultrasound Application on Protein Yield and Fate of Alkaloids during Lupin Alkaline Extraction Process.

The objective of this work is to elucidate the fate of quinolizidine alkaloids (QA) during the lupin protein extraction process assisted with ultrasound and the evaluation of the nutritional and functional properties of the protein fraction. Proximal characterization, concentration of anti-nutritional compounds, amino acid profile and protein solubility profile of flours from three lupin species were (L. albus, L. angustifolius and L. mutabilis) assessed. The result showed a significant difference (p < 0.05) in protein concentration, fat, total alkaloids and particle size between the three species flours. Based on these parameters, the most different Lupinus species (L. mutabilis and L. angustifolius) were chosen to study the behavior of the protein fraction in terms of functionality, composition and resistance to thermal treatments. The results obtained for L. mutabilis described the ultrasound effect as beneficial for protein yield (14% more than control), QA reduction from bagasse (81% less than control) and protein isolate production (50% less than control). On the other hand, L. angustifolius was more resistant to the ultrasound effect with no significant difference between treatments (10 and 15 min) and control but with the lower toxicity and better amino acid score. These results will be useful to design processes to assist in the objective of meeting the future protein demand of the population.

Effects of Post Anthesis Foliar Application of Sodium Selenite to Soybeans (Glycine max): Lipid Composition and Oil Stability.

This study aimed at determining whether applying selenium to soybean plants affected composition and oil oxidative stability of the seeds. Soybean was cultivated and sodium selenite (Selenite) added by foliar application (0, 200, or 300 g Selenite/Ha). Physical and chemical characterization was performed on the harvested seeds (thousand seed weight, bulk and true densities, fat, fiber, ash, protein, nitrogen free extract and selenium content). Soybean oil was tested in terms of Oxidation Induction Time (OIT), fatty acid, tocopherols, phytosterols, density, refractive index and saponification and iodine values. All seeds showed similar composition: crude fat (around 20%) and crude fiber (from 8.4 to 9.3%). Control seeds and those treated with 200 g Selenite/Ha contained higher protein concentration (37%), compared to the 300 g treatment (35.9%). All seeds showed similar ash content (7%). OIT values for both treatments were slightly lower (from 39.1 to 43.7 min) compared with 45.02 min in the control. Polyunsaturated fatty acids were higher for the 300 g Se/Ha (50.2%) compared with 48.2 to 49.4%of the other treatments. All samples showed similar phytosterols and tocopherols concentrations. Results showed that OIT values maintained an inverse relationship with selenium content, suggesting that foliar fertilization enhanced oil oxidation or acted as a pro-oxidant at the applied rates.

Hydrothermal treatment of maize: Changes in physical, chemical, and functional properties.

The objective of this work was to assess the effects of a traditional parboiling treatment on physical, chemical and functional properties of yellow maize kernels. For this, maize kernels were subjected to the three main stages of a traditional parboiling process (soaking, steaming, and drying) at different moisture contents (15%, 25%, or 35%), and different pressure steaming times (0, 15, or 30 min). Kernels were evaluated for physical and chemical changes, while manually generated endosperm fractions were further evaluated for nutritional and functional changes. The parboiling process negatively altered the maize kernels properties by increasing the number of kernels with burst pericarp and decreasing the total carotenoid content in the endosperm by 42%. However, the most intense conditions (35% moisture and 30 min steam) lowered the number of broken kernels by 41%, and the number of stress cracks by 36%. Results also demonstrated that soaking enhanced the nutritional value of soaked yellow maize by increasing the thiamine content and the bound phenolic content in the endosperm fraction up to 102%. The proper implementation of this hydrothermal treatment could lead to significant enhancements in nutritional and functionality of maize products.

Phenolic-Protein Interactions: Effects on Food Properties and Health Benefits.

Phenolic-protein interactions (PPI), which naturally occur in most food systems, are being intentionally designed to enhance functional performance of phenolic compounds (PC). PPI have been primarily associated with changes related to sensorial, nutritional, and nutraceutical features of foods. Furthermore, these interactions affect properties such as astringency, protein digestibility, absorption, and bioavailability of antioxidants. Therefore, new product development should pay attention to these interactions and not only on the concentration of PC. PPI protect PC from degradation due to enzymatic attack or pH changes in the lumen of the intestinal tract. Due to PPI, PC are delivered to the colon where they are metabolized by the microbiota and generate an antioxidant environment. Interactions with proteins also may enhance the antiproliferative activity of PC in some specific tumor cell lines. In this review, the effects of PPI that affect both food properties and health benefits are discussed.

Bioaccessibility, Intestinal Permeability and Plasma Stability of Isorhamnetin Glycosides from Opuntia ficus-indica (L.).

Isorhamnetin glycosides are representative compounds of Opuntia ficus-indica that possess different biological activities. There is slight information about the changes in bioaccessibility induced by the glycosylation pattern of flavonoids, particularly for isorhamnetin. In this study, the bioaccessibility and permeability of isorhamnetin glycosides extracted from O. ficus-indica were contrasted with an isorhamnetin standard. Also, the plasma stability of these isorhamnetin glycosides after intravenous administration in rats was evaluated. Recoveries of isorhamnetin after oral and gastric digestion were lower than that observed for its glycosides. After intestinal digestion, isorhamnetin glycosides recoveries were reduced to less than 81.0%. The apparent permeability coefficient from apical (AP) to basolateral (BL) direction (Papp(AP-BL)) of isorhamnetin was 2.6 to 4.6-fold higher than those obtained for its glycosides. Isorhamnetin diglycosides showed higher Papp(AP-BL) values than triglycosides. Sugar substituents affected the Papp(AP-BL) of the triglycosides. Isorhamnetin glycosides were better retained in the circulatory system than the aglycone. After intravenous dose of the isorhamnetin standard, the elimination half-life was 0.64 h but increased to 1.08 h when the O. ficus-indica extract was administered. These results suggest that isorhamnetin glycosides naturally found in O. ficus-indica could be a controlled delivery system to maintain a constant plasmatic concentration of this important flavonoid to exert its biological effects in vivo.

Mycochemical Changes Induced by Selenium Enrichment in P. ostreatus Fruiting Bodies.

The effects of selenium enrichment on the biological efficiency, phenolic compounds, amino acid profile, antioxidant capacity, and cellular antioxidant activity (CAA) were evaluated in Pleurotus ostreatus fruiting bodies (FB) harvested during three sequential flushes. Sodium selenate was used to reach selenium content of 17.5 or 5.8 mg/kg in the sorghum straw substrate. Biological efficiency and total selenium content increased. One of the main differences among treatments was in ergothioneine content, an indicator of oxidative stress that was positively related with valine and isoleucine contents and negatively related to leucine and phenylalanine. Besides ergothioneine, nucleosides derived from adenine and uracyl were the major peaks observed in all treatments, and coumaric and ferulic acids were found in the bound phenolics extract. Selenium enrichment also affected the antioxidant capacity, and particularly the methanolic extract obtained from the second flush of FB cultivated in selenium-enriched substrate (17.5 mg/kg) had the best CAA.

Cancer cell specific cytotoxic effect of Rhoeo discolor extracts and solvent fractions.

ETHNOPHARMACOLOGICAL RELEVANCE: Traditional or folk medicine has led to the discovery of important bioactive substances used in several health-related areas. Phytochemicals in Rhoeo discolor (R. discolor) extracts have proven to have important cancer cell specific cytotoxic activity. In the present research, we determined the cytotoxic effect of extracts of R. discolor, a plant commonly used in Mexico for both medicinal and ornamental purposes. AIM OF THE STUDY: We evaluated the cytotoxic effects against three representative human cancer cell lines: HT-29 colon cancer, Hep-G2 liver cancer and PC-3 prostate cancer cell lines, as well as a control fibroblast cell line NIH 3T3. MATERIALS AND METHODS: Ten different crude extracts were tested along with fractions derived from the five most bioactive crude extracts. Analytical data, HPLC-MS-TOF, revealed a high content of phenolic compounds such as anthocyanins, ferulic, vanillic, chlorogenic and p-coumaric acid in the extracts. Phenolic compounds have previously been reported as health beneficial with antioxidant and potential cancer specific cytotoxic effects. RESULTS: Studies revealed that low concentrations of these crude bioactive extracts (10µg/ml) and their fractions (50µg/ml) were effective as cancer specific cytotoxic agents, since they caused a significant proliferation inhibition on cancer cell lines (up to 94.2% in HT-29, 92.9% in Hep-G2 and 61.8% in PC-3 of apoptosis induction) with little harm to the control cell line (no higher than 28.3% apoptosis induction), and, importantly, the most effective extracts were mainly water, methanol and ethanol based. CONCLUSIONS: These results suggest that a diet containing these compounds may function as a medical aid or chemoprotective.

Delivery of Flavonoids and Saponins from Black Bean (Phaseolus vulgaris) Seed Coats Incorporated into Whole Wheat Bread.

Cereal-based products can be used as vehicles for the delivery of relevant bioactive compounds since they are staple foods for most cultures throughout the world. The health promoting benefits of flavonoids and saponins contained in black bean seed coats have been previously described. In the present work, the effect of adding flavonoids and saponins from black bean seed coat to the typical yeast-leavened whole wheat bread formulation in terms of bread features, organoleptic properties and phytochemical profile was studied. The retention of bioactive compounds was determined and the inhibitory effects of in vitro enzyme digested samples on two colon cancer cell lines (Caco-2 and HT29) was evaluated. The addition of bioactive compounds did not significantly affect baking properties or texture parameters. Among organoleptic properties of enriched breads, only crumb color was affected by the addition of bioactive compounds. However, the use of whole wheat flour partially masked the effect on color. More than 90% of added flavonoids and saponins and 80% of anthocyanins were retained in bread after baking. However, saponins were reduced more than 50% after the in vitro enzyme digestion. The black bean seed coat phytochemicals recovered after in vitro enzyme digestion of enriched breads significantly reduced by 20% the viability of colon cancer cells without affecting standard fibroblast cells (p < 0.05).

Characterization and Quantitation of Triterpenoid Saponins in Raw and Sprouted Chenopodium berlandieri spp. (Huauzontle) Grains Subjected to Germination with or without Selenium Stress Conditions.

Pseudocereal Chenopodium berlandieri spp. (huauzontle) was evaluated to determine saponin composition. Saponins were evaluated in raw and germinated grains subjected to chemical stress induced by sodium selenite. Analysis by liquid chromatography coupled with ELSD detector revealed the presence of 12 saponins, identified according to compounds previously assayed in Chenopodium quinoa. Saponins found at the highest concentrations in raw grains were derived from oleanolic and phytolaccagenic acids. Total saponin concentration significantly decreased in germinated compared to raw grains due to the significant loss of 90.1% and 95.7% of the phytolaccagenic acid without and with chemical selenium stress, respectively. The most abundant saponin in germinated sprouts decreased during normal germination. Interestingly, the concentration of this particular saponin significantly increased during the Se-induced stress germination. Chemical stress with selenium salts proved to change the saponin composition in geminated Chenopodium berlandieri spp. grains, therefore affecting their potential use as ingredient in the food industry.

Influence of Excipients and Spray Drying on the Physical and Chemical Properties of Nutraceutical Capsules Containing Phytochemicals from Black Bean Extract.

Black beans (Phaseolus vulgaris L.) are a rich source of flavonoids and saponins with proven health benefits. Spray dried black bean extract powders were used in different formulations for the production of nutraceutical capsules with reduced batch-to-batch weight variability. Factorial designs were used to find an adequate maltodextrin-extract ratio for the spray-drying process to produce black bean extract powders. Several flowability properties were used to determine composite flow index of produced powders. Powder containing 6% maltodextrin had the highest yield (78.6%) and the best recovery of flavonoids and saponins (>56% and >73%, respectively). The new complexes formed by the interaction of black bean powder with maltodextrin, microcrystalline cellulose 50 and starch exhibited not only bigger particles, but also a rougher structure than using only maltodextrin and starch as excipients. A drying process prior to capsule production improved powder flowability, increasing capsule weight and reducing variability. The formulation containing 25.0% of maltodextrin, 24.1% of microcrystalline cellulose 50, 50% of starch and 0.9% of magnesium stearate produced capsules with less than 2.5% weight variability. The spray drying technique is a feasible technique to produce good flow extract powders containing valuable phytochemicals and low cost excipients to reduce the end-product variability.

Yield and Textural Characteristics of Panela Cheeses Produced with Dairy-Vegetable Protein (Soybean or Peanut) Blends Supplemented with Transglutaminase.

The study evaluated panela cheeses made from dairy-plant protein blends, using soybean or peanut protein isolates, supplemented with transglutaminase (TG). Plant proteins were isolated using an alkaline extraction method followed by acid precipitation, and added to the dairy system in order to increase 50% or 100% the protein concentration. The total protein extraction for peanut and soybean isolates was 30.3% and 54.6%, respectively (based on initial protein content of sources), and no impairment of their essential amino acid profile was detected. Cheeses supplemented with TG and soybean showed the highest moisture and crude yield (>67.8% and 20.7%, respectively), whereas protein content was higher in the peanut isolate--added samples without TG (>67.4%). Cheese solids yield (ratio between final and initial solids) was higher for treatments with TG and 100% of plant protein addition (>50.7%). Regarding texture, 4 parameters were measured: hardness, cohesiveness, chewiness, and springiness. All cheeses containing soybean isolates and TG presented the highest chewiness and cohesiveness values, similar to those of the control treatment. Springiness was similar for all treatments, but hardness was higher in cheeses prepared with the peanut protein isolate added with TG. From these results it can be concluded that panela cheeses can be elaborated following a traditional procedure, but with the addition of soybean or peanut protein to the dairy ingredients. Cheeses containing these protein isolates showed higher protein than the milk control cheese and similar textural characteristics.

Antimicrobial Activity of Rhoeo discolor Phenolic Rich Extracts Determined by Flow Cytometry.

Traditional medicine has led to the discovery of important active substances used in several health-related areas. Phytochemicals in Rhoeo discolor extracts have proven to have important antimicrobial activity. In the present study, our group determined the antimicrobial effects of extracts of Rhoeo discolor, a plant commonly used in Mexico for both medicinal and ornamental purposes. We evaluated the in vitro activity of phenolic rich extracts against specifically chosen microorganisms of human health importance by measuring their susceptibility via agar-disc diffusion assay and flow cytometry: Gram-positive Listeria innocua and Streptococcus mutans, Gram-negative Escherichia coli and Pseudomonas aeruginosa, and lastly a fungal pathogen Candida albicans. Ten different extracts were tested in eight different doses on all the microorganisms. Analytical data revealed a high content of phenolic compounds. Both agar-disc diffusion assay and flow cytometry results demonstrated that Pseudomonas aeruginosa was the least affected by extract exposure. However, low doses of these extracts (predominantly polar), in a range from 1 to 4 µg/mL, did produce a statistically significant bacteriostatic and bactericidal effect on the rest of the microorganisms. These results suggest the addition of certain natural extracts from Rhoeo discolor could act as antibacterial and antimycotic drugs or additives for foods and cosmetics.

Anti-inflammatory glycosylated flavonoids as therapeutic agents for treatment of diabetes-impaired wounds.

Diabetes is a chronic disease that affects more than 387 million people worldwide. About 20% of patients diagnosed with diabetes develop diabetic foot ulcerations (DFU). Standard treatment of DFU includes wound debridement, infection control, revascularization and, in general, the acceleration of the healing process. Topical ointments containing flavonoids exert beneficial effects in wound healing process. Flavonoids increase the migration and proliferation of fibroblasts and collagen synthesis. Furthermore, most flavonoids exert antibacterial and astringent activities that help in infection control. Additionally, flavonoids possess antioxidant and anti-inflammatory activities reducing the reactive oxygen species and modulating the inflammatory pathways, respectively. Bioactivity of flavonoids can vary according to source, chemical structure and glycosylation pattern. In summary, topical application of flavonoids reduces epithelialization and wound closure time of DFU in diabetic patients.

Topical anti-inflammatory effects of isorhamnetin glycosides isolated from Opuntia ficus-indica.

Opuntia ficus-indica (OFI) has been widely used in Mexico as a food and for the treatment of different health disorders such as inflammation and skin aging. Its biological properties have been attributed to different phytochemicals such as the isorhamnetin glycosides which are the most abundant flavonoids. Moreover, these compounds are considered a chemotaxonomic characteristic of OFI species. The aim of this study was to evaluate the effect of OFI extract and its isorhamnetin glycosides on different inflammatory markers in vitro and in vivo. OFI extract was obtained by alkaline hydrolysis of OFI cladodes powder and pure compounds were obtained by preparative chromatography. Nitric oxide (NO), cyclooxygenase-2 (COX-2), tumor necrosis factor- (TNF-) α, and interleukin- (IL-) 6 production were measured. NO production was tested in lipopolysaccharide-stimulated RAW 264.7 cells while in vivo studies were carried on croton oil-induced ear edema model. OFI extract and diglycoside isorhamnetin-glucosyl-rhamnoside (IGR) at 125 ng/mL suppressed the NO production in vitro (73.5 ± 4.8% and 68.7 ± 5.0%, resp.) without affecting cell viability. Likewise, IGR inhibited the ear edema (77.4 ± 5.7%) equating the indomethacin effects (69.5 ± 5.3%). Both IGR and OFI extract significantly inhibited the COX-2, TNF-α, and IL-6 production. IGR seems to be a suitable natural compound for development of new anti-inflammatory ingredient.

The effect of isorhamnetin glycosides extracted from Opuntia ficus-indica in a mouse model of diet induced obesity.

A diet rich in polyphenols can ameliorate some metabolic alterations associated with obesity and type 2 diabetes. Opuntia ficus-indica (OFI) is a plant rich in isorhamnetin glycosides and is highly consumed in Mexico. The purpose of this research was to determine the metabolic effect of an OFI extract on a mouse model of diet-induced obesity and in isolated pancreatic islets. OFI extract was added to a high fat (HF) diet at a low (0.3%) or high (0.6%) dose and administered to C57BL/6 mice for 12 weeks. Mice fed the HF diet supplemented with the OFI extract gained less body weight and exhibited significantly lower circulating total cholesterol, LDL cholesterol and HDL cholesterol compared to those fed the HF diet alone. The HF-OFI diet fed mice presented lower glucose and insulin concentration than the HF diet fed mice. However, the HF-OFI diet fed mice tended to have higher insulin concentration than control mice. The OFI extract stimulated insulin secretion in vitro, associated with increased glucose transporter 2 (GLUT2) and peroxisome proliferator-activated receptor gamma (PPARγ) mRNA content. Furthermore, the OFI extract improved glucose tolerance, and additionally increased energy expenditure. These metabolic improvements were associated with reduced adipocyte size, increased hepatic IRS1 tyr-608 and S6 K thr-389 phosphorylation. OFI isorhamnetin glycosides also diminished the hepatic lipid content associated with reduced mRNA expression of the endoplasmic reticulum stress markers and lipogenic enzymes and increased mRNA expression of genes related to fatty acid oxidation. Overall, the OFI extract prevented the development of metabolic abnormalities associated with diet-induced obesity.