Assessment of Polyphenols Bioaccessibility, Stability, and Antioxidant Activity of White Mugwort (Artemisia lactiflora Wall.) during Static In Vitro Gastrointestinal Digestion.

White mugwort (Artemisia lactiflora Wall.), a traditional Chinese medicine, has been widely consumed in different forms for health care purposes. In this study, the in vitro digestion model of INFOGEST was used to investigate the bioaccessibility, stability, and antioxidant activity of polyphenols from two different forms of white mugwort, including dried powder (P 50, 100, and 150 mg/mL) and fresh extract (FE 5, 15, and 30 mg/mL). During digestion, the bioaccessibility of TPC and antioxidant activity were influenced by the form and ingested concentration of white mugwort. The highest bioaccessibility of the total phenolic content (TPC) and relative antioxidant activity were found at the lowest P and FE concentrations, as calculated relative to the TPC and antioxidant activity of P-MetOH and FE-MetOH based on the dry weight of the sample. Post-digestion, in comparison to P, FE had higher bioaccessibility (FE = 287.7% and P = 130.7%), relative DPPH radical scavenging activity (FE = 104.2% and P = 47.3%), and relative FRAP (FE = 673.5% and P = 66.5%). Nine compounds, 3-caffeoylquinic acid, 5-caffeoylquinic acid, 3,5-di-caffeoylquinic acid, sinapolymalate, isovitexin, kaempferol, morin, rutin, and quercetin, identified in both samples were modified during digestion, yet still provided strong antioxidant activity. These findings suggest that white mugwort extract possesses a higher polyphenol bioaccessibility, showing great potential as a functional ingredient.

Anti-Inflammatory Activity of an In Vitro Digested Anthocyanin-Rich Extract on Intestinal Epithelial Cells Exposed to TNF-α.

BACKGROUND: The consumption of foods rich in anthocyanins (ACN) have been associated with beneficial properties in chronic inflammatory disorders such as intestinal bowel diseases (IBD). These effects were attributed not only to a direct antioxidant mechanism but also to the modulation of cell redox-dependent signaling. However, ACN bioavailability is low for their poor stability in the digestive tract, so ACN gastrointestinal digestion should be considered. METHODS: To have a more realistic knowledge of the effects of ACN, we performed an in vitro simulated gastrointestinal digestion of an ACN-rich purified and standardized bilberry and blackcurrant extract (BBE), followed by an evaluation of ACN composition modification (HPLC-DAD and pH differential method) and antioxidant activity (FRAP assay). Then, we studied the effects of BBE gastrointestinal extract on Caco-2 exposed to TNF-α. RESULTS: The results confirmed the high instability of ACN in the mild alkaline environment of the small intestine (17% recovery index). However, the digested BBE maintained part of its bioactivity. Additionally, BBE gastrointestinal extract inhibited the TNF-α-induced NF-κB pathway in Caco-2 and activated the Nrf2 pathway. CONCLUSIONS: Although ACN stability is affected by gastrointestinal digestion, the anti-inflammatory and antioxidant activity of digested extracts were confirmed; thus, the loss of ACN can probably be counterweighed by their metabolites. Then, ACN introduced by diet or food supplements could represent an approach for IBD prevention.

Accumulation of Sulforaphane and Alliin in Human Prostate Tissue.

Diets rich in cruciferous vegetables have been associated with a lower risk of incidence and progression of prostate cancer. Sulforaphane, an isothiocyanate derived from 4-methylsulphinylbutyl glucosinolate (glucoraphanin) that accumulates in certain of these vegetables, notably broccoli, has been implicated in their protective effects. Likewise, the consumption of garlic and its sulphur-containing compounds such as alliin have been associated with a reduction in risk of prostate cancer. In this study, we tested whether consuming glucoraphanin derived from broccoli seeds and alliin derived from garlic resulted in the occurrence of these potential bioactive compounds in the prostate, which may contribute to our understanding of the putative protective effects of these dietary components. We recruited 42 men scheduled for a trans-perineal prostate biopsy into a randomised, double-blinded, 2 × 2-factorial dietary supplement four-week intervention study, and 39 completed the study. The two active interventions were supplements providing glucoraphanin from broccoli (BroccoMax®) and alliin from garlic (Kwai Heartcare®). Following the intervention, prostate biopsy tissue was analysed for the presence of sulforaphane and its thiol conjugates and for alliin and associated metabolites. Sulforaphane occurred in significantly higher levels in the prostate tissue (both within the transition and peripheral zone) of men consuming the glucoraphanin containing supplements (p < 0.0001) compared to men not consuming these supplements. However, while alliin and alliin-derived metabolites were detected within the prostate, there was no significant difference in the concentrations of these compounds in the prostate of men consuming supplements derived from garlic compared to men not consuming these supplements.

Accumulation of Dietary S-Methyl Cysteine Sulfoxide in Human Prostate Tissue.

SCOPE: Observational studies have associated consumption of cruciferous vegetables with reduced risk of prostate cancer. This effect has been associated with the degradation products of glucosinolates-thioglycosides that accumulate within crucifers. The possible role of S-methyl cysteine sulfoxide, a metabolite that also accumulates in cruciferous vegetables, and its derivatives, in cancer prevention is relatively unexplored compared to glucosinolate derivatives. The hypothesis that consuming a broccoli soup results in the accumulation of sulfate (a SMCSO derivative) and other broccoli-derived metabolites in prostate tissue is tested. METHODS AND RESULTS: Eighteen men scheduled for transperineal prostate biopsy were recruited into a 4-week parallel single blinded diet supplementation study (NCT02821728). Nine men supplemented their diet with three 300 mL portions of a broccoli soup each week for four weeks prior to surgery. Analyses of prostate biopsy tissues reveal no detectable levels of glucosinolates and derivatives. In contrast, SMCSO is detected in prostate tissues of the participants, with significantly higher levels in tissue of men in the supplementation arm. SMCSO was also found in blood and urine samples from a previous intervention study with the identical broccoli soup. CONCLUSION: The consequences of SMCSO accumulation in prostate tissues and its potential role in prevention of prostate cancer remains to be investigated.

Contribution of the Glucosinolate Fraction to the Overall Antioxidant Potential, Cytoprotection against Oxidative Insult and Antimicrobial Activity of Eruca sativa Mill. Leaves Extract.

BACKGROUND: Eruca sativa Mill. (Brassicaceae) is commonly utilized as an ingredient in salads and also as a folk remedy to treat various diseases. OBJECTIVE: The objective of this study was to establish the contribution of the glucosinolate (GLS) fraction to the overall antioxidant, cytoprotection against oxidative insult and antimicrobial properties of the hydro-alcoholic extract of E. sativa leaves from Sicily (Italy), characterized phytochemically. MATERIALS AND METHODS: The antioxidant activity was evaluated by different in vitro systems. The cytoprotective effect against hydrogen peroxide (H2O2)-induced oxidative stress was tested in human peripheral blood mononuclear cells (PBMCs). The antimicrobial potential against bacteria and fungi was assayed by standard methods. RESULTS: E. sativa extract exhibited both radical scavenging (50% inhibitory concentration [IC50] 1.04 ± 0.04 mg/mL) and ferrous ions-chelating activity (IC50 0.327 ± 0.0032 mg/mL) and mild reducing power; the GLS fraction showed chelating ability only (IC50 0.225 ± 0.009 mg/mL). In the experimental model of H2O2-induced oxidative stress in human PBMCs, a significant cytoprotective effect and a suppression of reactive oxygen species production by both extract and GLS fraction were observed (P < 0.001). E. sativa extract displayed moderate antimicrobial activity against Gram-positive bacteria, and Staphylococcus aureus was the most sensitive strain (minimum inhibitory concentration 0.125 mg/mL), whereas the GLS fraction was not active. CONCLUSION: GLSs are not involved in the primary antioxidant activity of E. sativa leaf extract but they are, almost in part, responsible for its ferrous ion-chelating properties. Iron-chelating compounds in E. sativa extract may protect cells under conditions of oxidative stress, and GLSs might play a chief role in this effect. SUMMARY: Eruca sativa Mill. leaf extract exhibited antioxidant activity in different in vitro systems, whereas the glucosinolate (GLS) fraction showed Fe2+-chelating ability onlyA significant cytoprotective effect and a suppression of intracellular reactive oxygen species production by both extract and GLS fraction were observed in human peripheral blood mononuclear cellsE. sativa extract displayed moderate antimicrobial activity against Gram-positive bacteria, whereas the GLS fraction was not active. Abbreviations used: GLS: Glucosinolate; H2O2: Hydrogen peroxide; PBMCs: Peripheral blood mononuclear cells; IC50: 50% inhibitory concentration; MIC: Minimum inhibitory concentration.

Validated Method for the Characterization and Quantification of Extractable and Nonextractable Ellagitannins after Acid Hydrolysis in Pomegranate Fruits, Juices, and Extracts.

Pomegranates are one of the main highly valuable sources of ellagitannins. Despite the potential health benefits of these compounds, reliable data on their content in pomegranates and derived extracts and food products is lacking, as it is usually underestimated due to their complexity, diversity, and lack of commercially available standards. This study describes a new method for the analysis of the extractable and nonextractable ellagitannins based on the quantification of the acid hydrolysis products that include ellagic acid, gallic acid, sanguisorbic acid dilactone, valoneic acid dilactone, and gallagic acid dilactone in pomegranate samples. The study also shows the occurrence of ellagitannin C-glycosides in pomegranates. The method was optimized using a pomegranate peel extract. To quantify nonextractable ellagitannins, freeze-dried pomegranate fruit samples were directly hydrolyzed with 4 M HCl in water at 90 °C for 24 h followed by extraction of the pellet with dimethyl sulfoxide/methanol (50:50, v/v). The method was validated and reproducibility was assessed by means of an interlaboratory trial, showing high reproducibility across six laboratories with relative standard deviations below 15%. Their applicability was demonstrated in several pomegranate extracts, different parts of pomegranate fruit (husk, peels, and mesocarp), and commercial juices. A large variability has been found in the ellagitannin content (150-750 mg of hydrolysis products/g) and type (gallagic acid/ellagic acid ratios between 4 and 0.15) of the 11 pomegranate extracts studied.

Mixed pro- and anti-oxidative effects of pomegranate polyphenols in cultured cells.

In recent years, the number of scientific papers concerning pomegranate (Punica granatum L.) and its health properties has increased greatly, and there is great potential for the use of bioactive-rich pomegranate extracts as ingredients in functional foods and nutraceuticals. To translate this potential into effective strategies it is essential to further elucidate the mechanisms of the reported bioactivity. In this study HepG2 cells were supplemented with a pomegranate fruit extract or with the corresponding amount of pure punicalagin, and then subjected to an exogenous oxidative stress. Overall, upon the oxidative stress the gene expression and activity of the main antioxidant enzymes appeared reduced in supplemented cells, which were more prone to the detrimental effects than unsupplemented ones. No differences were detected between cells supplemented with the pomegranate juice or the pure punicalagin. Although further studies are needed due to the gaps existing between in vitro and in vivo studies, our results suggest caution in the administration of high concentrations of nutraceutical molecules, particularly when they are administered in concentrated form.

Lack of effect of bioactive-rich extracts of pomegranate, persimmon, nettle, dill, kale and Sideritis and isolated bioactives on platelet function.

BACKGROUND: The health benefits of fruit and vegetable-rich diets may be partly due to modulation of platelet activity by bioactive phytochemicals. The aim of this study was to investigate the effects of bioactive-rich plant extracts and isolated bioactive metabolites on platelet function. Blood samples (n =15 subjects) were treated with extracts of bioactive-rich plants consumed as traditional foods in the Black Sea region, or with human metabolites of the bioactives quercetin and sulforaphane. Platelet function was assessed using the PFA-100. RESULTS: None of the extracts containing various flavonoids, glucosinolates and other bioactives, or isolated bioactive metabolites of quercetin or sulforaphane, caused significant changes in PFA-100 closure time (CT). In contrast, the positive controls (aspirin and Abciximab) consistently caused significant increases in CT for the platelet agonists epinephrine and ADP, respectively. CONCLUSION: These data do not support the notion that these plant bioactives can improve human platelet function.

Bioactive-rich Sideritis scardica tea (mountain tea) is as potent as Camellia sinensis tea at inducing cellular antioxidant defences and preventing oxidative stress.

BACKGROUND: In several countries, tea (hot-water infusions of dried Camellia sinensis (CS) leaves) is a major source of antioxidant flavonoids, and its consumption has been associated with several favourable outcomes. Other plants used for the preparation of herbal teas are sources of phenolic antioxidant compounds; among them Sideritis scardica (SS) is used for the preparation of a popular drink throughout Eastern and Central Europe. We have compared the effects of an SS extract to a CS extract in HepG2 cells to set the scientific basis for the exploitation of other herbal teas in counteraction of oxidative stress. RESULTS: Although SS extract had a lower phenolic concentration and total antioxidant capacity than CS extract, their cellular antioxidant effects were similar. The different phenolic pattern of the extracts suggests that the protective activity is not limited to catechins. CONCLUSION: Although further research is needed, our data represent a first contribution for the evaluation of the potential effect of SS in increasing antioxidant defences. © 2013 Society of Chemical Industry.

Pro-oxidant effect of alpha-tocopherol in patients with type 2 diabetes after an oral glucose tolerance test--a randomised controlled trial.

BACKGROUND: As a part of a larger study investigating the effects of alpha-tocopherol on gene expression in type 2 diabetics we observed a pro-oxidant effect of alpha-tocopherol which we believe may be useful in interpreting outcomes of large intervention trials of alpha-tocopherol. METHODS: 19 type 2 diabetes subjects were randomised into two groups taking either 1200 IU/day of alpha-tocopherol or a matched placebo for 4 weeks. On day 0 and 29 of this study oxidative DNA damage was assessed in mononuclear cells from fasted blood samples and following a 2 h glucose tolerance test (GTT). RESULTS: On day 0 there was no significant difference in oxidative DNA damage between the two groups or following a GTT. On day 29 there was no significant difference in oxidative DNA damage in fasted blood samples, however following a GTT there was a significant increase in oxidative DNA damage in the alpha-tocopherol treatment group. CONCLUSION: High dose supplementation with alpha-tocopherol primes mononuclear cells from patients with type 2 diabetes for a potentially damaging response to acute hyperglycaemia.

Serum retinoids and beta-carotene as predictors of hip and other fractures in elderly women.

UNLABELLED: There is debate about the possible deleterious effect of excessive vitamin A exposure on fracture risk. In this nested case control study in older women (312 cases and 934 controls), serum retinol, retinyl palmitate, and beta-carotene were not associated with fracture risk, and there was no evidence of excess risk with multivitamin or cod liver oil supplementation. INTRODUCTION: Recent studies have suggested that higher vitamin A intake may account for a component of fracture risk within the general population and that supplemental vitamin A may be harmful even within recommended limits. No studies have examined the relationship between biochemical retinol status and fracture in older women. MATERIALS AND METHODS: We examined serum retinol, retinyl palmitate, and beta-carotene as predictors of incident hip and other fractures in a large prospective study of British women over the age of 75 years (n = 2606, 312 incident osteoporotic fractures, 92 incident hip fractures; mean follow-up duration, 3.7 years). Fasting blood samples (9:00-11:00 a.m.) were collected at baseline. Using a case-control design (three controls per case), serum retinol, retinyl palmitate, and beta-carotene were assessed as univariate predictors of incident osteoporotic fracture or hip fracture. Baseline BMD at the total hip, age, 25(OH)D, serum beta Crosslaps, bone-specific alkaline phosphatase, weight, height, and smoking were considered as covariates in a multivariate model. RESULTS: Serum retinol, retinyl palmitate, and beta-carotene were not significant univariate predictors of either hip fracture or any fracture (all p > 0.05; Cox proportional hazards regression). For all osteoporotic fractures, the hazard ratio (HR) was 0.92 (95% CI, 0.81-1.05) per 1 SD increase in serum retinol. Risk of any osteoporotic fracture was slightly less in the highest quartile of serum retinol compared with the lowest quartile (HR, 0.85; 95% CI, 0.69-1.05; p = 0.132) There was a tendency for increased serum retinol to predict benefit rather than harm in terms of BMD (r = 0.09, p = 0.002). Multivitamin or cod liver oil supplementation was associated with a significantly lower risk of any fracture (HR, 0.76; 95% CI, 0.60-0.96; p = 0.021). In multivariate analysis, only age, total hip BMD, and weight were associated with fracture risk (p < 0.05). CONCLUSIONS: We found no evidence to support any skeletal harm associated with increased serum indices of retinol exposure or modest retinol supplementation in this population.