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Telephone counseling intervention increases intakes of micronutrient- and phytochemical-rich vegetables, fruit and fiber in breast cancer survivors.

Although a large body of evidence suggests that diet may play an important role in cancer prevention, randomized controlled trials reported to date have not achieved sufficient increases in protective micronutrients and phytochemicals to adequately test the hypothesis that diet can reduce cancer risk. The Women's Healthy Eating and Living (WHEL) Study, a randomized controlled trial of the role diet modification may play in future breast cancer events, introduced an innovative theory-based telephone counseling intervention to teach participants to consume a high fiber, low fat diet emphasizing vegetables and fruits rich in carotenoids and other potentially protective phytochemicals. This report examines the baseline to 12-mo changes in dietary intakes of 2970 participants, assessed through 24-h recalls and validated with plasma carotenoid concentrations. At 12 mo, the intervention group reported a significantly increased daily vegetable intake (+vegetable juice) of 7.1 servings (+82%) and fruit intake of 3.9 servings (+18%). Fiber intake increased from 3.04 to 4.16 g/(MJ. d), whereas energy from fat decreased significantly from 28.6 to 23.7%. Plasma carotenoid concentrations increased significantly, i.e., alpha-carotene (+223%); beta-carotene (+87%); lutein (+29%); and lycopene (+17%). In the comparison group, dietary intake and plasma carotenoid concentrations were essentially identical to those of the intervention group at baseline and were unchanged at 12 mo. The WHEL Study showed that a telephone counseling intervention can achieve major increases in micronutrient- and phytochemical-rich vegetables, fruit and fiber intakes, enabling an investigation of the potential cancer preventive effects of these food components.

Adult↗

Cranberry and its phytochemicals: a review of in vitro anticancer studies.

This article reviews the existing research on the anticancer properties of cranberry fruit and key phytochemicals that are likely contributors to chemoprevention. Results from in vitro studies using a variety of tumor models show that polyphenolic extracts from Vaccinium macrocarpon inhibit the growth and proliferation of breast, colon, prostate, lung, and other tumors, as do flavonols, proanthocyanidin oligomers, and triterpenoids isolated from the fruit. The unique combination of phytochemicals found in cranberry fruit may produce synergistic health benefits. Possible chemopreventive mechanisms of action by cranberry phytochemicals include induction of apoptosis in tumor cells, reduced ornithine decarboxylase activity, decreased expression of matrix metalloproteinases associated with prostate tumor metastasis, and antiinflammatory activities including inhibition of cyclooxygenases. These findings suggest a potential role for cranberry as a dietary chemopreventive and provide direction for future research.

Animals↗

Phytochemical research using accelerator mass spectrometry.

Vegetables and fruits provide an array of microchemicals in the form of vitamins and secondary metabolites (phytochemicals) that may lower the risk of chronic disease. Tracing these phytochemicals at physiologic concentrations has been hindered by a lack of quantitative sensitivity for chemically equivalent tracers that could be used safely in healthy people. Accelerator mass spectrometry is a relatively new technique that provides the necessary sensitivity (in attomoles) and measurement precision (<3%) towards 14C-labeled phytochemicals for detailed kinetic studies in humans at dietary levels.

Food Analysis↗

Mechanistic Perspectives From Genomics and Pangenomics of Medicinal and Aromatic Plants: Linking Genome Architecture to Phytochemical Diversity.

Medicinal and aromatic plants (MAPs) produce a remarkable diversity of specialized metabolites with significant pharmaceutical, nutraceutical, and industrial value. Although advances in long-read sequencing, chromosome-scale genome assembly, and pangenomics have greatly expanded genomic resources, the mechanistic links between genome architecture and phytochemical diversity remain incompletely understood. The present review synthesizes current evidence describing how structural genomic variation may contribute to phytochemical diversity, while acknowledging that many proposed genome-to-metabolite relationships require further experimental validation. Examples illustrate how genome architecture is associated with specialized-metabolite biosynthesis through multiple regulatory processes. However, the strength of supporting evidence varies considerably among MAP species. Moreover, relatively few genome-to-metabolite relationships have been confirmed through direct functional validation. We further discuss how pangenomics, multiomics integration, genome editing, synthetic biology, and artificial intelligence support the discovery, validation, and engineering of specialized metabolic pathways. Casual conclusions are evaluated according to the strength of available evidence, highlighting where causal relationships have been experimentally established and where conclusions remain primarily association-based. Overall, this review provides an integrated conceptual and evidence-based perspective summarizing proposed relationships between genome architecture and phytochemical diversity and outlines future priorities for functional genomics, precision breeding, metabolic engineering, and sustainable utilization of MAPs.

artificial intelligence↗

Aging, exercise, and phytochemicals: promises and pitfalls.

Phytochemicals are emerging comprehensive and versatile sources of antioxidants to be consumed to enhance the body's defenses against harmful reactive oxygen species generated endogenously or exogenously. Tocols, favonoids, and phenolic acids compose the majority of this class of antioxidants, although more complex compounds may also be involved, such as ginsenosides. In vitro and in vivo studies have demonstrated convincingly that dietary supplementation of phytochemicals has beneficial effects against certain types of pathogenesis, disease, cancer, and aging. There is evidence that these effects are related to the ability of phytochemicals to promote the antioxidant defense system and reduce oxidative stress and damage in the cell. However, due to their structural and chemical diversity and complexity, many of the benefits as well as potential adverse effects remain to be examined.

Aging↗

Estrogenic and antiestrogenic activities of flavonoid phytochemicals through estrogen receptor binding-dependent and -independent mechanisms.

Members of the flavonoid class of phytochemicals have previously been demonstrated to possess estrogenic activity in a number of hormonally responsive systems. We have performed the present study to characterize the estrogenic and antiestrogenic activity of flavonoids in the estrogen receptor (ER)-positive MCF-7 human breast cancer cell line. Using an ER-dependent reporter gene assay and an ER competition binding assay, we have identified phytochemicals possessing estrogenic and antiestrogenic activities, which appeared to correlate directly with their capacity to displace [3H]estradiol from ER. Several flavonoids, including kaempferide, apigenin, and flavone, were distinct, in that their antiestrogenic activity did not appear to correlate with binding to ER, and therefore their suppression of estrogen-mediated gene transactivation and proliferation may occur independent of direct antagonism of the receptor. Further examination in HEK-293 cells transfected with ERalpha or ERbeta demonstrated potent antagonism with kaempferide and apigenin, while flavone was weakly antagonistic only toward ERP. These results suggest that the receptor binding-independent antiestrogenic chemicals may function through alternate signaling pathways as indirect ER modulators in a receptor- and cell type-specific manner. We conclude that antiestrogenic activities of flavonoid phytochemicals may occur through ER binding-dependent and -independent mechanisms and that the binding-independent antiestrogen activity of certain flavonoids is biologically significant in regulation of breast cancer cell proliferation.

Binding, Competitive↗

Phytochemical mimicry of reproductive hormones and modulation of herbivore fertility by phytoestrogens.

Plants have physical and chemical mechanisms for defense from attack by animals. Phytochemical defenses that protect plants from attack by insects include antifeedants, insecticides, and insect growth regulators. Phytochemical options exist by which plants can modulate the fertility of the other major group of plant predators, vertebrate herbivores, and thereby reduce cumulative attacks by those herbivores. The success of such a defense depends upon phytochemical mimicry of vertebrate reproductive hormones. Phytoestrogens do mimic reproductive hormones and are proposed to be defensive substances produced by plants to modulate the fertility of herbivores.

Animals↗

Modulation of metabolic enzymes by dietary phytochemicals: a review of mechanisms underlying beneficial versus unfavorable effects.

In this review, we extensively survey the literature documenting the interaction of herbal components of the diet with metabolic enzymes. These interactions are mediated by the phytochemicals contained in herbs and can mechanistically occur at both transcriptional or post-transcriptional level. At the transcriptional level, dietary phytochemicals can cause induction of drug metabolizing enzymes (DME's: phase I and phase II) and transporters via nuclear hormone receptors, including the pregnane X receptor (PXR), the constitutive androstane receptor (CAR) or the aryl hydrocarbon receptor (AHR), as well as non-hormonal receptors, including the nuclear factor erythroid-derived 2 (NRF2) transcription factor. Herbs can also modulate the activity of DME's and transporters by competitive binding to or inactivation of the protein. There are cases where herbal constituents can undergo DME-mediated "bioactivation" resulting in DNA adduct formation and toxicity. The consequences of herb-DME interactions can be a) beneficial effects, such as cancer prevention, b) undesirable effects, such as pharmacokinetic interactions with co-administered drugs, c) harmful effects, such as organ toxicity or carcinogenesis. The molecular, cellular, and physiological mechanisms of herb-DME interactions will be discussed with examples of in vitro, animal or clinical studies of phytochemicals and in the context of human health benefits or risks.

Animals↗

Inhibition of aberrant proliferation and induction of apoptosis in pre-neoplastic human mammary epithelial cells by natural phytochemicals.

Aberrant proliferation and modulated apoptosis leading to impaired cellular homeostasis represent crucial early events in the multi-step carcinogenic process. Regulation of these perturbed biomarkers may predict efficacious prevention of cancer development. Present experiments on non-cancerous human mammary epithelial 184-B5 cells were designed to examine whether i) exposure to suspect environmental human carcinogen Benzo (a) pyrene (BP) alters the status of cell proliferation and apoptosis and ii) BP-induced alterations are modulated in response to select natural phytochemicals that inhibit rodent mammary tumorigenesis. Flow cytometric analysis, cellular immunoreactivity to proliferation specific and apoptosis specific gene products and anchorage-dependent colony formation represented quantitative endpoints. Cruciferous glucosinolate indole-3-carbinol (I3C), tea polyphenol (-) epigallo catechin gallate (EGCC) and soy isoflavone genistein (GEN) represented the chemopreventive test compounds. A single 24 h exposure to 39 lM BP resulted in a 50% decrease (P=0.02) in the ratio of quiescent (Q=G0) to proliferative (P=S + M) population in part due to increase in aberrantly proliferative cells. The BP-initiated cells also exhibited an 87.8% inhibition (P=0. 0001) in confluency-associated apoptosis and a concomitant decrease in cellular immunoreactivity to wild-type p53. Simultaneous treatment of cultures with BP + I3C, BP + EGCG and BP + GEN resulted in a 1.8- to 3.4-fold increase (P<0.01) in Q/P ratio and 1.8- to 6. 9-fold increase (P=0.001) in sub G0 (apoptotic) population. The induction of apoptosis was accompanied by enhanced p53 immunoreactivity (P<0.01). In long-term (21 day) experiments, BP treatment induced a 145.3% increase (P=0.001) in anchorage-dependent colony formation. This aberrant proliferation was inhibited by 44.2% to 65.3% (P=0.01) in the presence of the three phytochemicals. Thus, BP-induced aberrant proliferation is inhibited by the natural phytochemicals in part due to regulation of cell cycle progression and induction of p53 dependent apoptosis.

Anticarcinogenic Agents↗

Effects of citrus phytochemicals on liver and lung cytochrome P450 activity and on the in vitro metabolism of the tobacco-specific nitrosamine NNK.

NNK is a potent environmental carcinogen to which both smokers and nonsmokers are exposed. The response to NNK may be affected by factors including nutrition. We investigated the effects of five citrus phytochemicals on the in vitro metabolism of the tobacco-specific nitrosamine NNK and on the dealkylation of methoxyresorufin (MROD) and pentoxyresorufin (PROD) in liver and lung microsomes of the Syrian golden hamster. In the NNK metabolism experiments in vitro incubations contained 3 microCi [5-H3] NNK, 0.5 mg microsomal protein and 0.5 mumole of the citrus phytochemical diosmin, naringin, naringenin, quercetin or rutin. In the dealkylation studies incubations contained 0.5 microM methoxyresorufin or pentoxyresorufin, 0.5 mg microsomal protein and 0.5 mumole of citrus phytochemical. The major NNK metabolism pathway in hamster liver microsomes was NNK-reduction while in lung microsomes it was alpha-hydroxylation. The alpha-hydroxylation pathway produces metabolic products that methylate and pyridyloxobutylate DNA. Naringenin, a metabolite of naringin, and quercetin were the most potent inhibitors of alpha-hydroxylation of NNK in both liver and lung microsomes. This inhibition correlated with a potent inhibition of MROD and PROD activity in liver but not in lung microsomes. The metabolic activation of NNK is associated with cytochrome P450 isoforms 1A1, 1A2, 2B1, 2D6 and 2E1. Our results suggest that naringenin and quercetin from citrus fruits inhibit the activity of cytochrome P450 (CYP) isoforms that activate NNK and may afford protection against NNK-induced carcinogenesis.

Animals↗

[Biologically-active phytochemicals in vegetable food].

Phytochemicals constitute a heterogeneous group of substances and evidence for their role in the protective effect on human health, when their dietary intake is significant, is emerging. These compounds have biological properties as antioxidant activity, modulation of detoxification enzymes, stimulation of the immune system, decrease of platelet aggregation and modulation of hormone metabolism. Glucosinolates and widely group of polyphenols, including the main category of flavonoids, are examined. Since their weak estrogenic activity is of interest at present, isoflavones are discussed at length. Numerous factors affect the phytochemical content and availability in plants; these factors include environmental conditions and industrial or domestic processing. The bioavailability of phytochemicals can be influenced by intrinsic factors in food and/or in human, in general the substances are little adsorbed, largely metabolized and rapidly eliminated. For this reason it is advisable that their consumption is constant in the time to maintain high concentrations of metabolites in the blood.

Biological Availability↗

Phytochemical intakes of the Fijian population.

The dietary intakes of major phytochemicals in Fijian population were estimated from the consumption of 90 plant foods reported in five major surveys conducted in Fiji from 1952 to 2001. These surveys included the Naduri Longitudinal study, for which food intake data were collected on four occasions in 1952, 1953, 1963 and 1994), the 1982 and 1993 National Nutritional Surveys, the 1996 Suva-Nausori Corridor cross-sectional study, the 1999 Verata cross-sectional study, and the 2001 Fiji Food Choice study. It was found that the Fijian population generally had low intakes of total phenols (275 mg/day), and total flavonoids (17.5 mg/day), but high intake of total carotenoids (20 mg/day), in comparisons with the intakes of other populations reported in literature. It has been speculated that the change of eating patterns resulting in the low intakes of phytochemicals may have partly contributed to the increase in the nutritionally chronic disease morbidity and mortality among the Fijians. It is further recommended that the traditional Fijian food patterns with high fruits and vegetables should be revived, and the consumption of sweet potato leaves and drumstick leaves, both of which were rich in phytochemicals, should be promoted.

Adolescent↗

Phytochemical Characterization and Effects of Randia monantha Benth. Leaf and Fruit Extracts on the Viability of Human Cancer Cell Lines.

Randia monantha, commonly known as crucetillo, is a medicinal plant traditionally used in Mexico to treat conditions such as diabetes, venomous animal bites, and cancer; however, its effects on cancer cell viability remain underexplored. In this study, hexane, ethyl acetate, and methanolic extracts from the leaves and fruits of Randia monantha were phytochemically characterized and evaluated for their effects on cell viability in HeLa cervical cancer and DU-145 prostate cancer cell lines using the MTT assay. Phytochemical analyses revealed differences in metabolite composition across solvents of varying polarity and plant tissues. Methanolic leaf extracts contained higher levels of terpenoids and polyphenols and produced the greatest reduction in HeLa cell viability, with an estimated IC50 of 4.87 &#xb5;g/mL after 48 h of treatment. In contrast, DU-145 cells exhibited a different response pattern depending on the extract evaluated. Correlation analysis suggested that flavonoids were associated with reduced HeLa cell viability. Overall, leaf extracts produced greater reductions in cancer cell viability than fruit extracts, highlighting leaves as a promising but comparatively underexplored source of bioactive compounds in Randia monantha.

Humans↗

The potential of LC-NMR in phytochemical analysis.

The coupling of high performance liquid chromatography with nuclear magnetic resonance spectroscopy (LC-NMR) is one of the most powerful methods for the separation and structural elucidation of unknown compounds in mixtures. The recent progress in pulse field gradients and solvent suppression, the improvement in probe technology, and the construction of high field magnets have given a new stimulus to this technique, which has emerged since the mid 1990s as a very efficient method for the on-line identification of organic molecules. LC-NMR thus represents a potentially interesting complementary technique to LC-UV-MS in phytochemical analysis for the detailed on-line structural analysis of natural products. Recent applications have fully demonstrated the usefulness of this technique. A brief review of the applications of LC-NMR in natural product chemistry is presented in this paper, and a summary of the basic principles and modes of operation of LC-NMR is provided. Selected examples of LC-NMR analyses of plant metabolites in crude extracts or in enriched fractions are outlined and used to illustrate the different strategies for employing the technique. The practical possibilities and limitations of LC-NMR in its application to the analysis of crude plant extracts are discussed by means of several examples. Analytical strategies involving LC multi-coupled (hyphenated) techniques for the chemical screening and dereplication of crude plant extracts are presented. An analysis of the future development of the technique with respect to its application in phytochemical analysis is also given.

Biochemistry↗

Optimization of CZE for analysis of phytochemical bioactive compounds.

Advantages of CZE such as high efficiency, low cost, short analysis time, and easy implementation result in its wide applications for analysis of phytochemical bioactive compounds (e.g. flavonoids, alkaloids, terpenoids, phenolic acid, saponins, anthraquinones and coumarins). However, several aspects, including sample preparation, separation, and detection have significant effects on CZE analysis. Therefore, optimization of these procedures is necessary for development of the method. In this review, sample preparation such as extraction method and preconcentration, separation factors including buffer type, concentration and pH, additives, voltage and temperature, as well as detection, e.g. direct and indirect UV detection, LIF and MS were discussed for optimization of CZE analysis on phytochemical bioactive compounds. The optimized strategies were also reviewed.

Biological Products↗

Phytochemical phenolics in organically grown vegetables.

Fruit and vegetable intake is inversely correlated with risks for several chronic diseases in humans. Phytochemicals, and in particular, phenolic compounds, present in plant foods may be partly responsible for these health benefits through a variety of mechanisms. Since environmental factors play a role in a plant's production of secondary metabolites, it was hypothesized that an organic agricultural production system would increase phenolic levels. Cultivars of leaf lettuce, collards, and pac choi were grown either on organically certified plots or on adjacent conventional plots. Nine prominent phenolic agents were quantified by HPLC, including phenolic acids (e. g. caffeic acid and gallic acid) and aglycone or glycoside flavonoids (e. g. apigenin, kaempferol, luteolin, and quercetin). Statistically, we did not find significant higher levels of phenolic agents in lettuce and collard samples grown organically. The total phenolic content of organic pac choi samples as measured by the Folin-Ciocalteu assay, however, was significantly higher than conventional samples (p < 0.01), and seemed to be associated with a greater attack the plants in organic plots by flea beetles. These results indicated that although organic production method alone did not enhance biosynthesis of phytochemicals in lettuce and collards, the organic system provided an increased opportunity for insect attack, resulting in a higher level of total phenolic agents in pac choi.

Acids, Carbocyclic↗

Control of Aspergillus growth and aflatoxin production using natural maize phytochemicals under different conditions of water activity.

The effects of the natural phytochemicals trans-cinnamic acid (CA) and ferulic acid (FA) alone at concentrations of 1-25 mM and in 16 combinations (M: mixtures) on growth and aflatoxin B(1) production by Aspergillus flavus Link and A. parasiticus Speare were evaluated. Studies on growth rate and aflatoxin B(1) production were carried out in vitro in relation to a water activity a(w) of 0.999, 0.971, 0.955 and 0.937. Overall, CA at concentrations of 10 and 20 mM and FA-CA mixtures M3 (20 + 5 mM respectively), M8 (25 + 5 mM), M9 (1 + 10 mM), M10 (10 + 10 mM), M11 (20 + 10 mM), M12 (25 + 10 mM), M13 (1 + 20 mM), M14 (10 + 20 mM), M15 (20 + 20 mM) and M16 (25 + 20 mM) were the treatments most effective at inhibiting growth of the four species assayed. All strains were much more sensitive to all natural phytochemicals tested on growth rate at a(w) = 0.937. CA and the FA-CA mixtures M1 (1 + 1 mM respectively), M4 (25 + 1 mM), M5 (1 + 5 mM), M6 (10 + 1 mM), M7 (20 + 1 mM), M8 (25 + 5 mM), M9 (1 + 10 mM), M10 (10 + 10 mM), M11 (20 + 10 mM), M12 (25 + 10 mM), M13 (1 + 20 mM), M14 (10 + 20 mM), M15 (20 + 20 mM) and M16 (25 + 20 mM) completely inhibited aflatoxin B(1) production by all strains at a(w) = 0.999, 0.971, 0.955 and 0.937. Decreased aflatoxin B(1) levels in comparison with the control were observed with FA at 1, 10, 20 and 25 mM with the strains RCM89, RCM108 and RCM38 at a(w) = 0.971, 0.955 and 0.999 respectively. The data show that CA and FA can be considered as effective fungitoxicants for A. flavus and A. parasiticus in in vitro assay. The information obtained is part of an ongoing study to determine their application at the storage level.

Aflatoxins↗

The effects of phytochemical pesticides on the growth of cultured invertebrate and vertebrate cells.

A range of cultured cells of invertebrate and vertebrate origin was grown in the presence of a number of phytochemical pesticides to test the effect of the latter on cell proliferation. The main observation was that azadirachtin was a potent inhibitor of insect cell replication, with an EC50 of 1.5 x 10(10) M against Spodoptera cells and of 6.3 x 10(9) M against Aedes albopictus cells, whilst affecting mammalian cells only at high concentrations (> 10(-4) M). As expected, the other phytochemical pesticides, except for rotenone, had little effect on the growth of the cultured cells. Rotenone was highly effective in inhibiting the growth of insect cells (EC50:10(-8) M) but slightly less toxic towards mammalian cells (EC50:2 x 10(-7) M). Neem terpenoids other than azadirachtin and those very similar in structure significantly inhibited growth of the cell cultures, but to a lesser degree. The major neem seed terpenoids, nimbin and salannin, for example, inhibited insect cell growth by 23% and 15%, respectively.

Animals↗