Polyphenolic Characterization and Anti-Inflammatory Effect of In Vitro Digested Extracts of Echinacea purpurea L. Plant Parts in an Inflammatory Model of Human Colon Cells.

Echinacea purpurea L. (EP) preparations are globally popular herbal supplements known for their medicinal benefits, including anti-inflammatory activities, partly related to their phenolic composition. However, regarding their use for the management of inflammation-related intestinal diseases, the knowledge about the fate of orally ingested constituents throughout the human gastrointestinal tract and the exposition of in vitro digested extracts in relevant inflammatory models are unknown. This study investigated for the first time the impact of in vitro gastrointestinal digestion (INFOGEST) on the phenolic composition and anti-inflammatory properties of EP extracts from flowers (EF), leaves (EL), and roots (ER) on IL-1ß-treated human colon-derived CCD-18Co cells. Among the seven hydroxycinnamic acids identified using HPLC-UV-MS/MS, chicoric and caftaric acids showed the highest concentrations in EL, followed by EF and ER, and all extracts exerted significant reductions in IL-6, IL-8, and PGE2 levels. After digestion, despite reducing the bioaccessibility of their phenolics, the anti-inflammatory effects were preserved for digested EL and, to a lesser extent, for EF, but not for digested ER. The lower phenolic content in digested EF and ER could explain these findings. Overall, this study emphasizes the potential of EP in alleviating intestinal inflammatory conditions and related disorders.

Disposition of Dietary Polyphenols in Breast Cancer Patients' Tumors, and Their Associated Anticancer Activity: The Particular Case of Curcumin.

SCOPE: Some polyphenol-derived metabolites reach human breast cancer (BC) tissues at concentrations that induce cell senescence. However, this is unknown for isoflavones, curcuminoids, and lignans. Here, their metabolic profiling in normal (NT) and malignant (MT) mammary tissues of newly-diagnosed BC patients and the tissue-occurring metabolites' anticancer activity are evaluated. METHODS AND RESULTS: Patients (n = 26) consumed 3 capsules/day (turmeric, red clover, and flaxseed extracts plus resveratrol; 296.4 mg phenolics/capsule) from biopsy-confirmed diagnosis to surgery (5 ± 2 days) or did not consume capsules (n = 13). NT and MT, blood, and urine are analyzed by UPLC-QTOF-MS using targeted metabolomics. Anticancer activity was tested in MCF-7 and MDA-MB-231 BC cells. Mainly phase-II metabolites were detected (108, 84, 49, and 47 in urine, plasma, NT, and MT, respectively). Total metabolite concentrations reached 10.7 ± 11.1 and 2.5 ± 2.4 µmol L-1 in NT and MT, respectively. Free curcumin, but not its glucuronide, was detected in the tissues (1.1 ± 1.8 and 0.2 ± 0.2 µmol L-1 in NT and MT, respectively). Breast tissue-occurring metabolites' antiproliferation was mainly exerted in p53-wild-type MCF-7 cells by curcuminoids through cell cycle arrest, senescence, and apoptosis induction via p53/p21 induction, while isoflavone-derived metabolites exerted estrogenic-like activity. CONCLUSION: Curcuminoids could be coadjuvants that might help fight BC upon regular consumption.

Dietary Phenolics against Breast Cancer. A Critical Evidence-Based Review and Future Perspectives.

Breast cancer (BC) is the most common malignancy and the leading cause of cancer-related death in adult women worldwide. Over 85% of BC cases are non-hereditary, caused by modifiable extrinsic factors related to lifestyle, including dietary habits, which play a crucial role in cancer prevention. Although many epidemiological and observational studies have inversely correlated the fruit and vegetable consumption with the BC incidence, the involvement of their phenolic content in this correlation remains contradictory. During decades, wrong approaches that did not consider the bioavailability, metabolism, and breast tissue distribution of dietary phenolics persist behind the large currently existing gap between preclinical and clinical research. In the present review, we provide comprehensive preclinical and clinical evidence according to physiologically relevant in vitro and in vivo studies. Some dietary phenolics such as resveratrol (RSV), quercetin, isoflavones, epigallocatechin gallate (EGCG), lignans, and curcumin are gaining attention for their chemopreventive properties in preclinical research. However, the clinical evidence of dietary phenolics as BC chemopreventive compounds is still inconclusive. Therefore, the only way to validate promising preclinical results is to conduct clinical trials in BC patients. In this regard, future perspectives on dietary phenolics and BC research are also critically discussed.

Role of Apple Phytochemicals, Phloretin and Phloridzin, in Modulating Processes Related to Intestinal Inflammation.

Plant-derived food consumption has gained attention as potential intervention for the improvement of intestinal inflammatory diseases. Apple consumption has been shown to be effective at ameliorating intestinal inflammation symptoms. These beneficial effects have been related to (poly)phenols, including phloretin (Phlor) and its glycoside named phloridzin (Phldz). To deepen the modulatory effects of these molecules we studied: i) their influence on the synthesis of proinflammatory molecules (PGE2, IL-8, IL-6, MCP-1, and ICAM-1) in IL-1ß-treated myofibroblasts of the colon CCD-18Co cell line, and ii) the inhibitory potential of the formation of advanced glycation end products (AGEs). The results showed that Phlor (10-50 µM) decreased the synthesis of PGE2 and IL-8 and the formation of AGEs by different mechanisms. It is concluded that Phlor and Phldz, compounds found exclusively in apples, are positively associated with potential beneficial effects of apple consumption.

Buckwheat bioactive compounds, their derived phenolic metabolites and their health benefits.

SCOPE: Buckwheat (BW) consumption has been associated with a broad range of health benefits: antioxidant, anti-inflammatory and anticancer. These beneficial effects have been partially related to the presence of flavonoids. However, some of these compounds (i.e., rutin and quercetin) are metabolized in the gastrointestinal tract generating derived phenolic metabolites. In this study, we investigated the biological activity of rutin (Ru), quercetin (Q) an their derived phenolic metabolites 3,4-dihydroxyphenylacetic acid (3,4-DHPAA), 3-hydroxyphenylacetic acid (3-HPAA), and 4-hydroxy-3-methoxyphenylacetic acid (homovanillic acid, HVA). METHODS AND RESULTS: Q showed the highest antioxidant and reducing activity, and Ru the maximum chelating activity (85.33%). Antioxidant activity of 3,4-DHPAA was 5-fold higher than that of HVA, whereas their reducing activity was similar. The formation of methylglyoxal (MGO)-BSA and glucose-BSA (advanced glycation end products) was inhibited by Ru (98.5 and 92.7%), Q (95.6 and 89.1%) and 3,4-DHPPA (84.4.6 and 77.5%). Furthermore, Q (10-50 µM) and Ru (1-50 µM) downregulated the release of PGE2 , IL-8 and MCP-1, molecules involved in the inflammatory response, in IL1ß-inflamed myofibroblasts of colon CCD-18Co. CONCLUSION: This study suggests that BW phytochemicals and their phenolic metabolites may be responsible for the beneficial effects against chronic diseases attributed to BW consumption.

Buckwheat as a Functional Food and Its Effects on Health.

Buckwheat (BW) is a gluten-free pseudocereal that belongs to the Polygonaceae family. BW grain is a highly nutritional food component that has been shown to provide a wide range of beneficial effects. Health benefits attributed to BW include plasma cholesterol level reduction, neuroprotection, anticancer, anti-inflammatory, antidiabetic effects, and improvement of hypertension conditions. In addition, BW has been reported to possess prebiotic and antioxidant activities. In vitro and animal studies suggest that BW's bioactive compounds, such as D-chiro-inositol (DCI), BW proteins (BWP), and BW flavonoids (mainly rutin and quercetin) may be partially responsible for the observed effects. The purpose of this paper is to review the recent research regarding the health benefits of BW, in vitro and in vivo, focusing on the specific role of its bioactive compounds and on the mechanisms by which these effects are exerted.

Inhibition of quorum sensing (QS) in Yersinia enterocolitica by an orange extract rich in glycosylated flavanones.

Flavanones, flavonoids abundant in Citrus , have been shown to interfere with quorum sensing (QS) and affect related physiological processes. We have investigated the QS-inhibitory effects of an orange extract enriched in O-glycosylated flavanones (mainly naringin, neohesperidin, and hesperidin). The QS-inhibitory capacity of this extract and its main flavanone components was first screened using the bacteriological monitoring system Chromobacterium violaceum . We next examined the ability of the orange extract and of some of the flavanones to (i) reduce the levels of the QS mediators produced by Y. enterocolitica using HPLC-MS/MS, (ii) inhibit biofilm formation, and (iii) inhibit swimming and swarming motility. Additionally, we evaluated changes in the expression of specific genes involved in the synthesis of the lactones (yenI, yenR) and in the flagellar regulon (flhDC, fleB, fliA) by RT-PCR. The results showed that the orange extract and its main flavanone components inhibited QS in C. violaceum, diminished the levels of lactones secreted by Y. enterocolitica to the media, and decreased QS-associated biofilm maturation without affecting bacterial growth. Among the tested compounds, naringin was found to inhibit swimming motility. Exposure to the orange extract and (or) to naringin was also found to be associated with induction of the transcription levels of yenR, flhDC, and fliA. This work shows the in vitro QS-inhibitory effects of an orange extract enriched in flavanones against a human enteropathogen at doses that can be achieved through the diet and suggests that consumption of these natural extracts may have a beneficial antipathogenic effect.