Germination and its role in phenolic compound bioaccessibility for black mustard grains: A study using INFOGEST protocol.

Germination has been regarded as a promising natural process to improve the antioxidant properties of mustard. However, there ís one question to be solved in this area: does germination improve mustard phenolics' bioaccessibility? The aim of this study was to answer this question by using INFOGEST protocol to simulate in vitro digestion. Resveratrol, formononetin and cryptochlorogenic acid were identified for the first time as evaluated by liquid chromatography-mass spectrometry. In general, digestion positively impacted the antioxidant potential of soluble phenolics from non-germinated and germinated grains, which were probably released from cell wall matrix by digestive enzymes. Although digestion seemed to nullify the antioxidant improvement caused by germination, phenolic quantities were distinctive. The main difference was found for sinapic acid, as its concentration reached a value 1.75-fold higher in germinated digested mustard compared to non-germinated. The results obtained suggested that germination improved the phenolic bioaccessibility of mustard grains, which encourages its use and investigations.

Simulated gastrointestinal digestion/Caco-2 cell model to predict bioaccessibility and intestinal permeability of p-coumaric acid and p-coumaroyl derivatives in peanut.

Data concerning physiological recovery of whole peanut major phenolics throughout the gastrointestinal tract are scarce. In our study, the bioaccessibility and intestinal permeability of peanuts major phenolics were predicted by simulated digestion followed by Caco-2 cells monolayer model. Phenolics identification and quantification were performed by HPLC-ESI-QTOF-MS and HPLC-PDA, respectively. As results, p-coumaroyl conjugates with tartaric, sinapic and ferulic acids, and p-coumaric acid were the major phenolics found in the non-digested extract and in the digested and transported fractions. The in vitro bioaccessibility and Caco-2 cell transport of p-coumaric acid was 370% and 127%, respectively, while it was much lower for p-coumaroyl derivatives (7-100% and 14-31%, respectively). Nonetheless, the peroxyl scavenging activity remained unaltered, likely, at least partly, due to synergies between some phenolics, which concentration proportions changed throughout the experiment. Hence, there is indication that whole peanut is a source of bioavailable antioxidant phenolics.

Simulated gastrointestinal digestion/Caco-2 cell transport: Effects on biological activities and toxicity of a Brazilian propolis.

The objective was to assess the effect of gastrointestinal digestion/Caco-2 cell transport on biological activities and toxicity of the ethanolic extract of organic propolis from southern Brazil (EEOP1). As principal results, the EEOP1 deactivated the ROO•, HOCl and O2•- reactive oxygen species, attenuated NF-κB transcription factor activation, and decreased the release of TNF-α and IL-6 in macrophages after Caco-2 cell transport, while CXCL2/MIP-2 release was reduced after gastrointestinal digestion. Furthermore, the phytochemical profile monitored by HPLC-ESI-QTOF-MS changed, especially for lignans, lignan-precursors and phenolic acids. Conversely, the antimicrobial activity was observed only in the non-digested EEOP1. The EEOP1 lethal dose to kill 50 % of the Galleria mellonella larvae was 1.1 g/kg, and its digested fraction had no toxic effect. Hence, there is indication that some phytochemicals present in the EEOP1 are resistant to the gastrointestinal tract and maintain their biological activities, as expected for a functional food ingredient.

Bioaccessibility and uptake/epithelial transport of vitamin E: Discoveries and challenges of in vitro and ex vivo assays.

Vitamin E comprises compounds consisting of a chromanol ring and an isoprenoid side-chain, and is an essential lipid-soluble nutrient with several physiological functions. Vitamin E intake has been reported as inadequate for some populations. Only a fraction of dietary vitamin E is effectively released from the food matrix (bioaccessible fraction), absorbed (enterocyte uptake/epithelial transport) and transported in lipoproteins to reach the target tissues (bioavailable fraction), depending on the food structure, composition, and processing. Therefore, research concerning the fate of vitamin E through the gastrointestinal tract is of paramount importance for developing healthy foods and guiding effective public policies. The combination of simulated in vitro gastrointestinal digestion followed by intestinal epithelial transport and/or enterocyte uptake assays using ex vivo cell models has been successfully used to mimic the physiological conditions and predict the bioaccessibility and epithelial transport of compounds. The objective of this review was to summarize the current knowledge and challenges for predicting the bioaccessibility and uptake/epithelial transport of vitamin E by in vitro and ex vivo assays. Here, we revisited the metabolism of vitamin E and introduced in vitro and ex vivo methods for estimating the bioaccessibility and intestinal absorption of vitamin E. This review compiles data on vitamin E bioaccessibility in vitro and uptake/epithelial transport ex vivo for different food matrices, and discusses the factors that can affect their measurement. Additionally, co-culture approaches using hepatic lineages to assess vitamin E bioavailability are further presented.

Abilities of ß-Estradiol to interact with chemotherapeutic drugs, signal transduction inhibitors and nutraceuticals and alter the proliferation of pancreatic cancer cells.

Improving the effects of chemotherapy and reducing the side effects are important goals in cancer research. Various approaches have been examined to enhance the effectiveness of chemotherapy. For example, signal transduction inhibitors or hormonal based approaches have been included with chemo- or radio-therapy. MIA-PaCa-2 and BxPC-3 pancreatic ductal adenocarcinoma (PDAC) cells both express the estrogen receptor (ER). The effects of ß-estradiol on the growth of PDAC cells has not been examined yet the ER is expressed in PDAC cells. We have examined the effects of combining ß-estradiol with chemotherapeutic drugs, signal transcription inhibitors, natural products and nutraceuticals on PDAC. In most cases, inclusion of ß-estradiol with chemotherapeutic drugs increased chemosensitivity. These results indicate some approaches involving ß-estradiol which may be used to increase the effectiveness of chemotherapeutic and other drugs on the growth of PDAC.

Abilities of berberine and chemically modified berberines to interact with metformin and inhibit proliferation of pancreatic cancer cells.

Pancreatic cancer is devastating cancer worldwide with few if any truly effective therapies. Pancreatic cancer has an increasing incidence and may become the second leading cause of death from cancer. Novel, more effective therapeutic approaches are needed as pancreatic cancer patients usually survive for less than a year after being diagnosed. Control of blood sugar levels by the prescription drug metformin in diseases such as diabetes mellitus has been examined in association with pancreatic cancer. While the clinical trials remain inconclusive, there is hope that certain diets and medications may affect positively the outcomes of patients with pancreatic and other cancers. Other natural compounds may share some of the effects of metformin. One "medicinal" fruit consumed by millions worldwide is berberine (BBR). Metformin and BBR both activate AMP-activated protein kinase (AMPK) which is a key mediator of glucose metabolism. Glucose metabolism has been shown to be very important in cancer and its significance is increasing. In the following studies, we have examined the effects of metformin, BBR and a panel of modified BBRs (NAX compounds) and chemotherapeutic drugs on the growth of four different human pancreatic adenocarcinoma cell lines (PDAC). Interestingly, the effects of metformin could be enhanced by BBR and certain modified BBRs. Upon restoration of WT-TP53 activity in MIA-PaCa-2 cells, an altered sensitivity to the combination of certain NAX compounds and metformin was observed compared to the parental cells which normally lack WT-TP53. Certain NAX compounds may interact with WT-TP53 and metformin treatment to alter the expression of key molecules involved in cell growth. These results suggest a therapeutic approach by combining certain pharmaceutical drugs and nutraceuticals to suppress the growth of cancer cells.

Bioactive Fraction of Geopropolis from Melipona scutellaris Decreases Neutrophils Migration in the Inflammatory Process: Involvement of Nitric Oxide Pathway.

The aim of this study was to evaluate the activity of the ethanolic extract of geopropolis (EEGP) from Melipona scutellaris and its fractions on the modulation of neutrophil migration in the inflammatory process, and the participation of nitric oxide (NO) pathway, as well as to check the chemical profile of the bioactive fraction. EEGP and its aqueous fraction decreased neutrophil migration in the peritoneal cavity and also the interaction of leukocytes (rolling and adhesion) with endothelial cells. The levels of chemokines CXCL1/KC and CXCL2/MIP-2 were not altered after treatment with EEGP and the aqueous fraction. It was found that the injection of NO pathway antagonists abolished the EEGP and the aqueous fraction inhibitory activity on the neutrophil migration. The expression of intercellular adhesion molecule type 1 (ICAM-1) was reduced, and nitrite levels increased after treatment with EEGP and aqueous fraction. In the carrageenan-induced paw edema model, EEGP and the aqueous fraction showed antiedema activity. No pattern of flavonoid and phenolic acid commonly found in propolis samples of Apis mellifera could be detected in the aqueous fraction samples. These data indicate that the aqueous fraction found has promising bioactive substances with anti-inflammatory activity.