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Special Issue "Phytochemicals in Health and Disease"

A special issue of Nutrients (ISSN 2072-6643).

Deadline for manuscript submissions: closed (1 December 2018)

Special Issue Editor

Guest Editor
Dr. Francesca Giampieri

Department of Odontostomatologic and Specialized Clinical Sciences, Sez-Biochimica, Faculty of Medicine, Università Politecnica delle Marche, Via Ranieri 65, 60100 Ancona, Italy
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Interests: nutrition; health; bioactive compounds; polyphenols; antioxidants; free radicals; oxidative stress; aging; mitochodrial functionality; apoptosis; strawberry, honey

Special Issue Information

Dear Colleagues,

In the last few years, the potential role of dietary phytochemicals in the promotion of human health and in the prevention of chronic diseases has generated interest among worldwide researchers. It is widely accepted that the consumption of natural compounds, such as phytochemicals, confers protection against inflammation, oxidative stress, metabolic dysregulation and vascular dysfunction, reducing several risk factors for non-communicable pathologies, including obesity, diabetes, cardiovascular and neurological diseases and certain types of cancer. Nonetheless, many aspects remain to be still elucidated, such as the evaluation of their bioavailability and bioacessibility, the interaction with gut microbiota or the modulation of molecular mechanisms involved in cellular functions and cellular death. Based on these premises, there is an urgent need of studies evaluating the effects of dietary bioactive compounds from different fields of knowledge.

The main aim of the Special Issue on "Phytochemicals in Health and Disease" is to be an open forum where researchers may share their investigations and findings in this promising field and, thanks to the open access platform, increase their visibility and the chances to interact with industries and the production systems. Contributions to this issue, in the form of original research, both in vitro and in vivo, or review articles, may cover all aspects of phytochemicals; studies with multidisciplinary input are particularly welcome.

Dr. Francesca Giampieri
Guest Editor

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Keywords

  • polyphenols
  • bioactive compounds
  • functional foods
  • medicinal products
  • health
  • disease prevention
  • bioavailability
  • bioaccesibility
  • molecular targets
  • gut microbiota
  • inflammation
  • oxidative stress
  • vascular dysfunction
  • aging
  • mitochondrial functionality
  • apoptosis

Published Papers (21 papers)

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Open AccessArticle Phytochemicals of Cinnamomi Cortex: Cinnamic Acid, but not Cinnamaldehyde, Attenuates Oxaliplatin-Induced Cold and Mechanical Hypersensitivity in Rats
Nutrients 2019, 11(2), 432; https://doi.org/10.3390/nu11020432 (registering DOI)
Received: 3 January 2019 / Revised: 15 February 2019 / Accepted: 15 February 2019 / Published: 19 February 2019
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Abstract
A chemotherapy drug, oxaliplatin, induces cold and mechanical hypersensitivity, but effective treatments for this neuropathic pain without side effects are still lacking. We previously showed that Cinnamomi Cortex suppresses oxaliplatin-induced pain behaviors in rats. However, it remains unknown which phytochemical of Cinnamomi Cortex [...] Read more.
A chemotherapy drug, oxaliplatin, induces cold and mechanical hypersensitivity, but effective treatments for this neuropathic pain without side effects are still lacking. We previously showed that Cinnamomi Cortex suppresses oxaliplatin-induced pain behaviors in rats. However, it remains unknown which phytochemical of Cinnamomi Cortex plays a key role in that analgesic action. Thus, here we investigated whether and how cinnamic acid or cinnamaldehyde, major components of Cinnamomi Cortex, alleviates cold and mechanical allodynia induced by a single oxaliplatin injection (6 mg/kg, i.p.) in rats. Using an acetone test and the von Frey test for measuring cold and mechanical allodynia, respectively, we found that administration of cinnamic acid, but not cinnamaldehyde, at doses of 10, 20 and 40 mg/kg (i.p.) significantly attenuates the allodynic behaviors in oxaliplatin-injected rats with the strongest effect being observed at 20 mg/kg. Our in vivo extracellular recordings also showed that cinnamic acid (20 mg/kg, i.p.) inhibits the increased activities of spinal wide dynamic range neurons in response to cutaneous mechanical and cold stimuli following the oxaliplatin injection. These results indicate that cinnamic acid has an effective analgesic action against oxaliplatin-induced neuropathic pain through inhibiting spinal pain transmission, suggesting its crucial role in mediating the effect of Cinnamomi Cortex. Full article
(This article belongs to the Special Issue Phytochemicals in Health and Disease)
Open AccessArticle Deciphering the Molecular Mechanisms Sustaining the Estrogenic Activity of the Two Major Dietary Compounds Zearalenone and Apigenin in ER-Positive Breast Cancer Cell Lines
Nutrients 2019, 11(2), 237; https://doi.org/10.3390/nu11020237
Received: 12 November 2018 / Revised: 14 January 2019 / Accepted: 14 January 2019 / Published: 22 January 2019
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Abstract
The flavone apigenin and the mycotoxin zearalenone are two major compounds found in the human diet which bind estrogen receptors (ERs), and therefore influence ER activity. However, the underlying mechanisms are not well known. To unravel the molecular mechanisms that could explain the [...] Read more.
The flavone apigenin and the mycotoxin zearalenone are two major compounds found in the human diet which bind estrogen receptors (ERs), and therefore influence ER activity. However, the underlying mechanisms are not well known. To unravel the molecular mechanisms that could explain the differential effect of zearalenone and apigenin on ER-positive breast cancer cell proliferation, gene-reporter assays, chromatin immunoprecipitation (ChIP) experiments, proliferation assays and transcriptomic analysis were performed. We found that zearalenone and apigenin transactivated ERs and promoted the expression of estradiol (E2)-responsive genes. However, zearalenone clearly enhanced cellular proliferation, while apigenin appeared to be antiestrogenic in the presence of E2 in both ER-positive breast cancer cell lines, MCF-7 and T47D. The transcriptomic analysis showed that both compounds regulate gene expression in the same way, but with differences in intensity. Two major sets of genes were identified; one set was linked to the cell cycle and the other set was linked to stress response and growth arrest. Our results show that the transcription dynamics in gene regulation induced by apigenin were somehow different with zearalenone and E2 and may explain the differential effect of these compounds on the phenotype of the breast cancer cell. Together, our results confirmed the potential health benefit effect of apigenin, while zearalenone appeared to be a true endocrine-disrupting compound. Full article
(This article belongs to the Special Issue Phytochemicals in Health and Disease)
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Open AccessArticle Long-Term Impact of Neonatal Intake of Oleanolic Acid on the Expression of AMP-Activated Protein Kinase, Adiponectin and Inflammatory Cytokines in Rats Fed with a High Fructose Diet
Nutrients 2019, 11(2), 226; https://doi.org/10.3390/nu11020226
Received: 23 October 2018 / Revised: 6 December 2018 / Accepted: 7 December 2018 / Published: 22 January 2019
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Abstract
AMP-activated protein kinase (AMPK) is known to regulate both glucose and lipid metabolism, which play vital roles in the development of metabolic syndrome. One way of regulating AMPK is through hormonal activation using adiponectin. Patients diagnosed with type-2 diabetes (T2D) and obesity exhibit [...] Read more.
AMP-activated protein kinase (AMPK) is known to regulate both glucose and lipid metabolism, which play vital roles in the development of metabolic syndrome. One way of regulating AMPK is through hormonal activation using adiponectin. Patients diagnosed with type-2 diabetes (T2D) and obesity exhibit low adiponectin concentration levels in their blood. Moreover, studies have also shown that inflammatory processes play a significant role in the etiology of these metabolic diseases. In this study, the long-term effects of neonatal intake of oleanolic acid (OA) on the AMPK gene, genes associated with glucose transport and lipid metabolism, adiponectin levels, and inflammatory biomarkers in rats fed with a high fructose diet were investigated. Seven day old pups were randomly divided into five groups and treated as follows; 0.5% dimethylsulphoxide v/v in distilled water vehicle control (CON), oleanolic acid (OA, 60 mg/kg), high fructose diet (HF, 20% w/v), high fructose diet combined with oleanolic acid (HF+OA), and high fructose diet combined with metformin (HF+MET, 500 mg/kg). The treatments were administered once daily until day 14. The rats were then weaned at day 21 and fed standard rat chow and had ad libitum access to plain drinking water until day 112. The quantitative polymerase chain reaction (qPCR) was used to analyze the gene expressions of AMPK, Glut-4, Cpt-1, AdipoR1, AdipoR2, TNF-α, and IL-6 in the skeletal muscles. Bio-Plex Pro magnetic bead-based assay was used to measure plasma levels of inflammatory markers (TNF-α, IL-6, VEGF, and MCP-1) while ELISA kits were used to measure adiponectin concentration in blood plasma. The results obtained in this study showed that neonatal supplementation with OA significantly increased AMPK gene expression approximately ~4-fold in OA fed rats compared to those that were fed with HF alone. In addition, glut-4 gene expression was also significantly higher in the OA treatment group compared to all the other experimental groups except the CON group whereas Cpt-1 gene was more expressed when OA was administered alone. Together, these results indicated that OA can play a role in glucose and lipid metabolism gene regulation. Furthermore, the results showed that the OA group had ~1.5-fold increase in adiponectin concentration when comparedto the HF group. Moreover, HF increased levels of inflammatory cytokines, which was attenuated by neonatal administration of OA. Plasma concentration and gene expression in the skeletal muscle for TNF-α and IL-6 were significantly increased in rats that were treated with HF alone when compared to all the other groups. On the contrary, the high levels of TNF-α and IL-6 were reduced when OA was administered. These findings suggest that intake of oleanolic acid during the neonatal stage of development could be a potential strategic intervention for the long-term prevention of metabolic diseases such as T2D and obesity. Full article
(This article belongs to the Special Issue Phytochemicals in Health and Disease)
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Open AccessArticle Cytoprotective Effects of Mangiferin and Z-Ligustilide in PAH-Exposed Human Airway Epithelium in Vitro
Nutrients 2019, 11(2), 218; https://doi.org/10.3390/nu11020218
Received: 29 November 2018 / Revised: 9 January 2019 / Accepted: 15 January 2019 / Published: 22 January 2019
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Abstract
According to World Health Organisation (WHO) air pollution increases the risk of cardiovascular disorders, respiratory diseases, including COPD, lung cancer and acute respiratory infections, neuro-degenerative and other diseases. It is also known that various phytochemicals may mitigate such risks. This study tested if [...] Read more.
According to World Health Organisation (WHO) air pollution increases the risk of cardiovascular disorders, respiratory diseases, including COPD, lung cancer and acute respiratory infections, neuro-degenerative and other diseases. It is also known that various phytochemicals may mitigate such risks. This study tested if phytochemicals mangiferin (MNG) and Z-ligustilide (Z-LG) may protect PAH-exposed human lung bronchial epithelial cells (BEAS-2B). Organic PAH extract was obtained from the urban fine PM with high benzo(a)pyrene content collected in Eastern European mid-sized city during winter heating season. Cell proliferation traits and levels of intracellular oxidative stress were examined. Effect of MNG (0.5 µg/mL) alone or in combination with PAH on bronchial epithelium wound healing was evaluated. Both phytochemicals were also evaluated for their antioxidant properties in acellular system. Treatment with MNG produced strong cytoprotective effect on PAH-exposed cells (p < 0.01) while Z-LG (0.5 µg/mL) exhibited strong negative effect on cell proliferation in untreated and PAH-exposed cells (p < 0.001). MNG, being many times stronger antioxidant than Z-LG in chemical in vitro assays (p < 0.0001), was also able to decrease PAH-induced oxidative stress in the cell cultures (p < 0.05). Consequently MNG ameliorates oxidative stress, speeds up wound healing process and restores proliferation rate in PAH-exposed bronchial epithelium. Such protective effects of MNG in air pollution affected airway epithelium stimulate further research on this promising phytochemical. Full article
(This article belongs to the Special Issue Phytochemicals in Health and Disease)
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Open AccessFeature PaperArticle Improved Preventive Effects of Combined Bioactive Compounds Present in Different Blueberry Varieties as Compared to Single Phytochemicals
Nutrients 2019, 11(1), 61; https://doi.org/10.3390/nu11010061
Received: 29 November 2018 / Revised: 18 December 2018 / Accepted: 24 December 2018 / Published: 29 December 2018
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Abstract
Blueberries contain many different phytochemicals which might be responsible for their disease preventive properties. In a previously conducted human dietary intervention study, we showed that a 4-week intervention with blueberry–apple juice protected the participants against oxidative stress and modulated expression of genes involved [...] Read more.
Blueberries contain many different phytochemicals which might be responsible for their disease preventive properties. In a previously conducted human dietary intervention study, we showed that a 4-week intervention with blueberry–apple juice protected the participants against oxidative stress and modulated expression of genes involved in different genetic pathways contributing to the antioxidant response. The present study investigates the effect of different blueberry varieties (Elliot, Draper, Bluecrop, and Aurora, and the blueberry–apple juice from our previous human dietary intervention study), and four different single compounds (vitamin C, peonidin, cyanidin, and quercetin) on antioxidant capacity and gene expression changes in colonic cells in vitro, and compares the outcome with the earlier in vivo findings. The results demonstrate that all blueberry varieties as well as the blueberry–apple juice were more effective in reducing oxidative stress as compared to the single compounds (e.g., DNA strand break reduction: EC50: Elliot 8.3 mg/mL, Aurora and Draper 11.9 mg/mL, blueberry–apple juice 12.3 mg/mL, and Bluecrop 12.7 mg/mL; single compounds). In addition, the gene expression profiles (consisting of 18 selected genes from the in vivo study) induced by the blueberry varieties were more similar to the profile of the human intervention study (range 44–78%). The blueberry variety Elliot showed the strongest and most similar effects, almost 80% of gene expression modulations were similar compared to the in vivo results. From the single compounds (range 17–44%), quercetin induced the most comparable gene expression changes, i.e., 44%. This approach could be useful in agriculture for identifying crop varieties containing combinations of phytochemicals which show optimal preventive capacities. Full article
(This article belongs to the Special Issue Phytochemicals in Health and Disease)
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Open AccessArticle Changing to a Low-Polyphenol Diet Alters Vascular Biomarkers in Healthy Men after Only Two Weeks
Nutrients 2018, 10(11), 1766; https://doi.org/10.3390/nu10111766
Received: 26 October 2018 / Revised: 10 November 2018 / Accepted: 12 November 2018 / Published: 14 November 2018
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Abstract
Bioactive dietary compounds play a critical role in health maintenance. The relation between bioactive compound intake and cardiovascular health-related biomarkers has been demonstrated in several studies, although mainly with participants who have altered biochemical parameters (high blood pressure, high cholesterol, metabolic syndrome, etc.). [...] Read more.
Bioactive dietary compounds play a critical role in health maintenance. The relation between bioactive compound intake and cardiovascular health-related biomarkers has been demonstrated in several studies, although mainly with participants who have altered biochemical parameters (high blood pressure, high cholesterol, metabolic syndrome, etc.). The aim of this study was to evaluate if adopting a diet low in polyphenol-rich food for two weeks would affect vascular biomarkers in healthy men. In a crossover study, 22 healthy men were randomly assigned to their usual diet (UD), consuming healthy food rich in polyphenols, or to a low antioxidant diet (LAD), with less than two servings of fruit and vegetables per day and avoiding the intake of cocoa products, coffee and tea. As a marker of compliance, total polyphenols in urine were significantly lower after the LAD than after the UD (79 ± 43 vs. 123 ± 58 mg GAE/g creatinine). Nitric oxide levels were also reduced (52 ± 28 in LAD vs. 80 ± 34 µM in UD), although no significant changes in cellular adhesion molecules and eicosanoids were observed; however, an increasing ratio between thromboxane A2 (TXA2) and prostaglandin I2 (PGI2) was reached (p = 0.048). Thus, a slight dietary modification, reducing the consumption of polyphenol-rich food, may affect vascular biomarkers even in healthy individuals. Full article
(This article belongs to the Special Issue Phytochemicals in Health and Disease)
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Open AccessArticle Anti-Atherosclerotic Effect of a Polyphenol-Rich Ingredient, Oleactiv®, in a Hypercholesterolemia-Induced Golden Syrian Hamster Model
Nutrients 2018, 10(10), 1511; https://doi.org/10.3390/nu10101511
Received: 22 July 2018 / Revised: 8 October 2018 / Accepted: 10 October 2018 / Published: 15 October 2018
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Abstract
The development of nutraceutical ingredients has risen as a nutritional solution for health prevention. This study evaluated the effects of Oleactiv®, an ingredient developed for the prevention of atherogenesis, in hypercholesterolemic hamsters. Oleactiv® is a polyphenol-rich ingredient obtained from artichoke, [...] Read more.
The development of nutraceutical ingredients has risen as a nutritional solution for health prevention. This study evaluated the effects of Oleactiv®, an ingredient developed for the prevention of atherogenesis, in hypercholesterolemic hamsters. Oleactiv® is a polyphenol-rich ingredient obtained from artichoke, olive and grape extracts as part of fruit and vegetables commonly consumed within the Mediterranean diet. A total of 21 Golden Syrian hamsters were divided into three groups. The standard group (STD) was fed a normolipidemic diet for 12 weeks, while the control group (CTRL) and Oleactiv® goup (OLE) were fed a high-fat diet. After sacrifice, the aortic fatty streak area (AFSA), plasmatic total cholesterol (TC), high-density lipoproteins (HDL-C), non-HDL-C and triglycerides (TG), were assessed. The cholesterol efflux capacity (CEC) of hamster plasma was quantified using a radiolabeled technique in murine macrophages J774. OLE administration induced a significant reduction of AFSA (−69%, p < 0.0001). Hamsters of the OLE group showed a significant decrease of both non-HDL-C (−173 mmol/L, p < 0.05) and TG (−154 mmol/L, p < 0.05). Interestingly, OLE induced a significant increase of total CEC (+17,33%, p < 0,05). Oleactiv® supplementation prevented atheroma development and had positive effects on the lipid profile of hypercholesterolemic hamsters. The increased CEC underlines the anti-atherosclerotic mechanism at the root of the atheroma reduction observed. Full article
(This article belongs to the Special Issue Phytochemicals in Health and Disease)
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Open AccessArticle Momordica charantia Ethanol Extract Attenuates H2O2-Induced Cell Death by Its Antioxidant and Anti-Apoptotic Properties in Human Neuroblastoma SK-N-MC Cells
Nutrients 2018, 10(10), 1368; https://doi.org/10.3390/nu10101368
Received: 10 September 2018 / Revised: 20 September 2018 / Accepted: 22 September 2018 / Published: 24 September 2018
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Abstract
Oxidative stress, which is induced by reactive oxygen species (ROS), causes cellular damage which contributes to the pathogenesis of neurodegenerative diseases. Momordica charantia (MC), a traditional medicinal plant, is known to have a variety of health benefits, such as antidiabetic, anti-inflammatory, and antioxidant [...] Read more.
Oxidative stress, which is induced by reactive oxygen species (ROS), causes cellular damage which contributes to the pathogenesis of neurodegenerative diseases. Momordica charantia (MC), a traditional medicinal plant, is known to have a variety of health benefits, such as antidiabetic, anti-inflammatory, and antioxidant effects. However, it is unknown whether MC has protective effects against oxidative stress-induced neuronal cell death. The aim of this study was to investigate the potential action of MC on oxidative stress induced by H2O2. First, we tested whether the pretreatment of Momordica charantia ethanol extract (MCEE) attenuates H2O2-induced cell death in human neuroblastoma SK-N-MC cells. MCEE pretreatment significantly improved cell viability and apoptosis that deteriorated by H2O2. Further, MCEE ameliorated the imbalance between intracellular ROS production and removal through the enhancement of the intracellular antioxidant system. Intriguingly, the inhibition of apoptosis was followed by the blockage of mitochondria-dependent cell death cascades and suppression of the phosphorylation of the mitogen-activated protein kinase signaling (MAPKs) pathway by MCEE. Taken together, MCEE was shown to be effective in protecting against H2O2-induced cell death through its antioxidant and anti-apoptotic properties. Full article
(This article belongs to the Special Issue Phytochemicals in Health and Disease)
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Open AccessArticle Platycodon grandiflorum Saponins Ameliorate Cisplatin-Induced Acute Nephrotoxicity through the NF-κB-Mediated Inflammation and PI3K/Akt/Apoptosis Signaling Pathways
Nutrients 2018, 10(9), 1328; https://doi.org/10.3390/nu10091328
Received: 8 August 2018 / Revised: 11 September 2018 / Accepted: 14 September 2018 / Published: 19 September 2018
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Abstract
Although cisplatin is a potent chemotherapeutic agent against cancers, its clinical application is seriously limited by its severe side effects of nephrotoxicity. Previous studies reported that saponins isolated from the roots of Platycodon grandiflorum (PGS) exerted protective effects in various animal models of [...] Read more.
Although cisplatin is a potent chemotherapeutic agent against cancers, its clinical application is seriously limited by its severe side effects of nephrotoxicity. Previous studies reported that saponins isolated from the roots of Platycodon grandiflorum (PGS) exerted protective effects in various animal models of renal injury, with no confirmation on cisplatin-induced injury. This study was designed to investigate the protective effect of PGS (15 and 30 mg/kg) on cisplatin-induced kidney injury in mice. The levels of serum creatinine (CRE) and blood urea nitrogen (BUN), and renal histopathology demonstrated the protective effect of PGS against cisplatin-induced kidney injury. PGS exerted anti-inflammation effects via suppressing nuclear factor-kappa B (NF-κB) activation and alleviating the cisplatin-induced increase in inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), tumor necrosis factor-α (TNF-α), and interleukin-1β (IL-1β) in kidney tissues. The expressions of phosphorylation of phosphatidylinositol 3-kinase/protein kinase B and its downstream apoptotic factors, such as Bcl-2 and caspase families were regulated by PGS in a dose-dependent manner. In conclusion, PGS exerted kidney protection effects against cisplatin-induced kidney injury by inhibiting the activation of NF-κB and regulating PI3K/Akt/apoptosis signaling pathways in mice. Full article
(This article belongs to the Special Issue Phytochemicals in Health and Disease)
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Open AccessArticle Acute Epigallocatechin 3 Gallate (EGCG) Supplementation Delays Gastric Emptying in Healthy Women: A Randomized, Double-Blind, Placebo-Controlled Crossover Study
Nutrients 2018, 10(8), 1122; https://doi.org/10.3390/nu10081122
Received: 23 July 2018 / Revised: 15 August 2018 / Accepted: 18 August 2018 / Published: 20 August 2018
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Abstract
Background: Epigallocatechin 3 Gallate (EGCG) appears to act in appetite control through hormonal modulation. However, there is a lack of elucidation of EGCG’s action mechanisms, especially in humans. The aim of this study was to evaluate the effects of acute EGCG supplementation [...] Read more.
Background: Epigallocatechin 3 Gallate (EGCG) appears to act in appetite control through hormonal modulation. However, there is a lack of elucidation of EGCG’s action mechanisms, especially in humans. The aim of this study was to evaluate the effects of acute EGCG supplementation on gastric emptying and its relation to blood hormones, glucose and appetite perceptions in healthy women. Methods: 22 healthy adult women were included in a randomized, double-blind, placebo-controlled crossover study. On two separate occasions, 1 week apart from each other, we offered 800 mg of corn starch (placebo) or 752 mg of EGCG. Appetite was assessed through gastric emptying; perceptions of hunger, desire to eat and satiation; and plasma insulin, adiponectin, leptin and glucose concentrations. The evaluations were carried out in fasting, 30, 90 and 150 min after supplementation. Results: EGCG supplementation induced higher relative gastric volume at 30 and 90 min. Satiation at 90 min was higher in the EGCG group. Adiponectin concentrations at 150 min were higher with EGCG, but no difference was found for glucose, insulin and leptin concentrations. Conclusions: Acute EGCG supplementation is able to delay gastric emptying in healthy women to a small, but statistically significant extent. This study was registered at the Brazilian Registry of Clinical Trials (ReBEC) as RBR-9svwrv. Full article
(This article belongs to the Special Issue Phytochemicals in Health and Disease)
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Open AccessArticle Discovering Health Benefits of Phytochemicals with Integrated Analysis of the Molecular Network, Chemical Properties and Ethnopharmacological Evidence
Nutrients 2018, 10(8), 1042; https://doi.org/10.3390/nu10081042
Received: 6 July 2018 / Revised: 3 August 2018 / Accepted: 6 August 2018 / Published: 8 August 2018
Cited by 1 | PDF Full-text (1621 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Identifying the health benefits of phytochemicals is an essential step in drug and functional food development. While many in vitro screening methods have been developed to identify the health effects of phytochemicals, there is still room for improvement because of high cost and [...] Read more.
Identifying the health benefits of phytochemicals is an essential step in drug and functional food development. While many in vitro screening methods have been developed to identify the health effects of phytochemicals, there is still room for improvement because of high cost and low productivity. Therefore, researchers have alternatively proposed in silico methods, primarily based on three types of approaches; utilizing molecular, chemical or ethnopharmacological information. Although each approach has its own strength in analyzing the characteristics of phytochemicals, previous studies have not considered them all together. Here, we apply an integrated in silico analysis to identify the potential health benefits of phytochemicals based on molecular analysis and chemical properties as well as ethnopharmacological evidence. From the molecular analysis, we found an average of 415.6 health effects for 591 phytochemicals. We further investigated ethnopharmacological evidence of phytochemicals and found that on average 129.1 (31%) of the predicted health effects had ethnopharmacological evidence. Lastly, we investigated chemical properties to confirm whether they are orally bio-available, drug available or effective on certain tissues. The evaluation results indicate that the health effects can be predicted more accurately by cooperatively considering the molecular analysis, chemical properties and ethnopharmacological evidence. Full article
(This article belongs to the Special Issue Phytochemicals in Health and Disease)
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Open AccessArticle Volatile Terpenes and Brain Function: Investigation of the Cognitive and Mood Effects of Mentha × Piperita L. Essential Oil with In Vitro Properties Relevant to Central Nervous System Function
Nutrients 2018, 10(8), 1029; https://doi.org/10.3390/nu10081029
Received: 12 July 2018 / Revised: 31 July 2018 / Accepted: 2 August 2018 / Published: 7 August 2018
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Abstract
Background: Extracts of several members of the monoterpene-rich Lamiaceae sub-family Nepetoideae, including those from the Salvia (sage), Melissa (Lemon balm) and Rosmarinus (rosemary) genera, evince cognitive and mood effects in humans that are potentially related to their effects on cholinergic and [...] Read more.
Background: Extracts of several members of the monoterpene-rich Lamiaceae sub-family Nepetoideae, including those from the Salvia (sage), Melissa (Lemon balm) and Rosmarinus (rosemary) genera, evince cognitive and mood effects in humans that are potentially related to their effects on cholinergic and GABAergic neurotransmission. To date, despite promising in vitro properties, the cognitive and mood effects of the closely related Mentha spicata (spearmint) and Mentha piperita (peppermint) remain unexplored. This study therefore assessed the human cognitive/mood effects of the M. spicata/piperita essential oil with the most promising, brain-relevant in vitro properties according to pre-trial in vitro screening. Design: Organic spearmint and peppermint (Mentha spicata/piperita) essential oils were pre-screened for neurotransmitter receptor binding and acetylcholinesterase (AChE) inhibition. In a double-blind, placebo-controlled, balanced cross-over study, 24 participants (mean age 25.2 years) consumed single doses of encapsulated placebo and 50 µL and 100 µL of the most promising essential oil (peppermint with nicotinic/GABAA receptor binding and AChE inhibitory properties, that increased calcium influx in a CAD cell neuronal model). Psychological functioning was assessed with mood scales and a range of standardised, cognitively demanding tasks pre-dose and at 1, 3 and 6 h post-dose. Results: The highest (100 µL) dose of essential oil improved performance on the cognitively demanding Rapid Visual Information Processing task (RVIP) at 1 h and 3 h post-dose and both doses attenuated fatigue and improved performance of the Serial 3 s subtraction task at 3 h post-dose. Conclusion: Peppermint (Mentha piperita) essential oil with high levels of menthol/menthone and characteristic in vitro cholinergic inhibitory, calcium regulatory and GABAA/nicotinic receptor binding properties, beneficially modulated performance on demanding cognitive tasks and attenuated the increase in mental fatigue associated with extended cognitive task performance in healthy adults. Future investigations should consider investigating higher doses. Full article
(This article belongs to the Special Issue Phytochemicals in Health and Disease)
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Open AccessArticle Aqueous Extract of Pepino (Solanum muriactum Ait) Leaves Ameliorate Lipid Accumulation and Oxidative Stress in Alcoholic Fatty Liver Disease
Nutrients 2018, 10(7), 931; https://doi.org/10.3390/nu10070931
Received: 15 June 2018 / Revised: 12 July 2018 / Accepted: 13 July 2018 / Published: 20 July 2018
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Abstract
Chronic alcohol intake leads to alcoholic fatty liver. The pathogenesis of alcoholic fatty liver is related to abnormal lipid accumulation, oxidative stress, endotoxins, and cytokines. Solanum muricatum Ait. (Pepino) is a plant food commonly cultivated in the Penghu island, Taiwan. Previous studies indicated [...] Read more.
Chronic alcohol intake leads to alcoholic fatty liver. The pathogenesis of alcoholic fatty liver is related to abnormal lipid accumulation, oxidative stress, endotoxins, and cytokines. Solanum muricatum Ait. (Pepino) is a plant food commonly cultivated in the Penghu island, Taiwan. Previous studies indicated that the aqueous extract of pepino was able to attenuate diabetic progression via its antioxidative and anti-inflammatory effects. However, the mechanisms of the antioxidative and anti-inflammatory effects of pepino leaf in preventing alcoholic fatty liver remain unknown. In this study, Lieber–DeCarli ethanol-containing liquid diet was used to induce alcoholic hepatic injury in C57BL/6 mice. The hepatoprotective effects and the related mechanisms of aqueous extract of pepino leaf (AEPL) were examined. Our results showed that 2% AEPL treatments protected the liver from ethanol-induced injury through reducing serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), total cholesterol (TC) and triglyceride (TG) (all p < 0.05). AEPL had the effects in improving the ethanol-induced lipid accumulation in mice under histological examination. Molecular data indicated that the anti-lipid accumulation effect of AEPL might be mediated via inducing hepatic levels of phospho-adenosine monophosphate-activated kinase (p-AMPK) and peroxisome proliferator-activated receptor (PPAR)-α, and reducing the expressions of hepatic lipogenic enzymes, including sterol regulatory element-binding protein (SREBP)-1c, acetyl-CoA carboxylase (ACC), and fatty acid synthase (FAS) (all p < 0.05). AEPL also decreased hepatic levels of thiobarbituric acid relative substances (TBARS), tumor necrosis factor (TNF)-α, and interleukin (IL)-6, as well as the expression of nuclear factor kappa B (NF-κB) (all p < 0.05). Moreover, AEPL significantly elevated the activities of superoxide dismutase (SOD), catalase, and glutathione peroxidase (GPx), and glutathione (GSH) content compared to the ethanol-fed group (all p < 0.05). Our present study suggests that AEPL could protect the liver against ethanol-induced oxidative injury and lipid accumulation. Full article
(This article belongs to the Special Issue Phytochemicals in Health and Disease)
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Open AccessArticle Caffeic Acid Targets AMPK Signaling and Regulates Tricarboxylic Acid Cycle Anaplerosis while Metformin Downregulates HIF-1α-Induced Glycolytic Enzymes in Human Cervical Squamous Cell Carcinoma Lines
Nutrients 2018, 10(7), 841; https://doi.org/10.3390/nu10070841
Received: 22 May 2018 / Revised: 23 June 2018 / Accepted: 25 June 2018 / Published: 28 June 2018
Cited by 3 | PDF Full-text (2834 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The small molecules, natural antioxidant Caffeic Acid (trans-3,4-Dihydroxycinnamic acid CA) and anti-diabetic drug Metformin (Met), activate 5′-adenosine monophosphate-activated protein kinase (AMPK) and interfere with metabolic reprogramming in human cervical squamous carcinoma cells. Here, to gain more insight into the ability of CA, Met [...] Read more.
The small molecules, natural antioxidant Caffeic Acid (trans-3,4-Dihydroxycinnamic acid CA) and anti-diabetic drug Metformin (Met), activate 5′-adenosine monophosphate-activated protein kinase (AMPK) and interfere with metabolic reprogramming in human cervical squamous carcinoma cells. Here, to gain more insight into the ability of CA, Met and the combination of both compounds to impair aerobic glycolysis (the “Warburg effect”) and disrupt bioenergetics of cancer cells, we employed the cervical tumor cell lines C-4I and HTB-35/SiHa. In epithelial C-4I cells derived from solid tumors, CA alleviated glutamine anaplerosis by downregulation of Glutaminase (GLS) and Malic Enzyme 1 (ME1), which resulted in the reduction of NADPH levels. CA treatment of the cells altered tricarboxylic acid (TCA) cycle supplementation with pyruvate via Pyruvate Dehydrogenase Complex (PDH), increased ROS formation and enhanced cell death. Additionally, CA and CA/Met evoked intracellular energetic stress, which was followed by activation of AMPK and the impairment of unsaturated FA de novo synthesis. In invasive HTB-35 cells, Met inhibited Hypoxia-inducible Factor 1 (HIF-1α) and suppressed the expression of the proteins involved in the “Warburg effect”, such as glucose transporters (GLUT1, GLUT3) and regulatory enzymes of glycolytic pathway Hexokinase 2 (HK2), 6-Phosphofructo-2-Kinase/Fructose-2,6-Biphosphatase 4 (PFKFB4), Pyruvate Kinase (PKM) and Lactate Dehydrogenase A (LDH). Met suppressed the expression of c-Myc, BAX and cyclin-D1 (CCND1) and evoked apoptosis in HTB-35 cells. In conclusion, both small molecules CA and Met are capable of disrupting energy homeostasis, regulating oxidative metabolism/glycolysis in cervical tumor cells in regard to specific metabolic phenotype of the cells. CA and Met may provide a promising approach in the prevention of cervical cancer progression. Full article
(This article belongs to the Special Issue Phytochemicals in Health and Disease)
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Open AccessArticle Protective Effects of Ellagitannin-Rich Strawberry Extracts on Biochemical and Metabolic Disturbances in Rats Fed a Diet High in Fructose
Nutrients 2018, 10(4), 445; https://doi.org/10.3390/nu10040445
Received: 12 March 2018 / Revised: 29 March 2018 / Accepted: 30 March 2018 / Published: 4 April 2018
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Abstract
The present study compares the effects of two dietary strawberry extracts rich in monomeric (ME) or dimeric (DE) ellagitannins (ETs) on gastrointestinal, blood and tissue biomarkers in Wistar rats fed high-fructose diets. Both strawberry extracts beneficially affect the antioxidant status and lipid profile [...] Read more.
The present study compares the effects of two dietary strawberry extracts rich in monomeric (ME) or dimeric (DE) ellagitannins (ETs) on gastrointestinal, blood and tissue biomarkers in Wistar rats fed high-fructose diets. Both strawberry extracts beneficially affect the antioxidant status and lipid profile of the liver and serum. The ME extract shows a greater ability to inhibit lipid peroxidation in kidneys, more effectively decreases serum and liver triglycerides, and exerts greater anti-inflammatory effects in blood serum than the DE extract. The DE extract significantly reduces the activity of microbial enzymes in the cecum. These effects might be associated with higher cecum and urine levels of ET metabolites in rats fed with ME than in rats fed with DE. In conclusion, the diet-induced fructose-related disturbances observed in biochemical parameters are regulated by both extracts; nevertheless, the beneficial effects of the ME extract are mostly associated with systemic parameters, while those of the DE extracts are associated with local microbial activity. Full article
(This article belongs to the Special Issue Phytochemicals in Health and Disease)
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Review

Jump to: Research

Open AccessReview Hop Compounds: Extraction Techniques, Chemical Analyses, Antioxidative, Antimicrobial, and Anticarcinogenic Effects
Nutrients 2019, 11(2), 257; https://doi.org/10.3390/nu11020257
Received: 7 December 2018 / Revised: 10 January 2019 / Accepted: 18 January 2019 / Published: 24 January 2019
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Abstract
Hop plants comprise a variety of natural compounds greatly differing in their structure and properties. A wide range of methods have been developed for their isolation and chemical analysis, as well as for determining their antioxidative, antimicrobial, and antigenotoxic potentials. This contribution provides [...] Read more.
Hop plants comprise a variety of natural compounds greatly differing in their structure and properties. A wide range of methods have been developed for their isolation and chemical analysis, as well as for determining their antioxidative, antimicrobial, and antigenotoxic potentials. This contribution provides an overview of extraction and fractionation techniques of the most important hop compounds known for their health-promoting features. Although hops remain the principal ingredient for providing the taste, stability, and antimicrobial protection of beer, they have found applications in the pharmaceutical and other food industries as well. This review focuses on numerous health-promoting effects of hops raging from antioxidative, sedative, and anti-inflammatory potentials, over anticarcinogenic features to estrogenic activity. Therefore, hops should be exploited for the prevention and even healing of several prevalent diseases like cardiovascular disorders and various cancer types. New ideas for future studies on hops are finally presented: computational investigations of chemical reactivities of hop compounds, nanoencapsulation, and synergistic effects leading to a higher bioavailability of biologically active substances as well as the application of waste hop biomass from breweries for the production of high-added-value products in accordance with the biorefinery concept. Full article
(This article belongs to the Special Issue Phytochemicals in Health and Disease)
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Open AccessReview An Update on the Effects of Glyceollins on Human Health: Possible Anticancer Effects and Underlying Mechanisms
Nutrients 2019, 11(1), 79; https://doi.org/10.3390/nu11010079
Received: 29 November 2018 / Revised: 20 December 2018 / Accepted: 23 December 2018 / Published: 3 January 2019
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Abstract
Biologically active plant-based compounds, commonly referred to as phytochemicals, can influence the expression and function of various receptors and transcription factors or signaling pathways that play vital roles in cellular functions and are then involved in human health and diseases. Thus, phytochemicals may [...] Read more.
Biologically active plant-based compounds, commonly referred to as phytochemicals, can influence the expression and function of various receptors and transcription factors or signaling pathways that play vital roles in cellular functions and are then involved in human health and diseases. Thus, phytochemicals may have a great potential to prevent and treat chronic diseases. Glyceollins, a group of phytoalexins that are isolated from soybeans, have attracted attention because they exert numerous effects on human functions and diseases, notably anticancer effects. In this review, we have presented an update on the effects of glyceollins in relation to their potential beneficial roles in human health. Despite a growing number of studies suggesting that this new family of phytochemicals can be involved in critical cellular pathways, such as estrogen receptor, protein kinase, and lipid kinase signaling pathways, future investigations will be needed to better understand their molecular mechanisms and their specific significance in biomedical applications. Full article
(This article belongs to the Special Issue Phytochemicals in Health and Disease)
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Open AccessReview Redox Homeostasis and Natural Dietary Compounds: Focusing on Antioxidants of Rice (Oryza sativa L.)
Nutrients 2018, 10(11), 1605; https://doi.org/10.3390/nu10111605
Received: 12 October 2018 / Revised: 25 October 2018 / Accepted: 26 October 2018 / Published: 1 November 2018
Cited by 1 | PDF Full-text (1165 KB) | HTML Full-text | XML Full-text
Abstract
Redox homeostasis may be defined as the dynamic equilibrium between electrophiles and nucleophiles to maintain the optimum redox steady state. This mechanism involves complex reactions, including nuclear factor erythroid 2-related factor 2 (Nrf2) pathway, activated by oxidative stress in order to restore the [...] Read more.
Redox homeostasis may be defined as the dynamic equilibrium between electrophiles and nucleophiles to maintain the optimum redox steady state. This mechanism involves complex reactions, including nuclear factor erythroid 2-related factor 2 (Nrf2) pathway, activated by oxidative stress in order to restore the redox balance. The ability to maintain the optimal redox homeostasis is fundamental for preserving physiological functions and preventing phenotypic shift toward pathological conditions. Here, we reviewed mechanisms involved in redox homeostasis and how certain natural compounds regulate the nucleophilic tone. In addition, we focused on the antioxidant properties of rice and particularly on its bioactive compound, γ-oryzanol. It is well known that γ-oryzanol exerts a variety of beneficial effects mediated by its antioxidant properties. Recently, γ-oryzanol was also found as a Nrf2 inducer, resulting in nucleophilic tone regulation and making rice a para-hormetic food. Full article
(This article belongs to the Special Issue Phytochemicals in Health and Disease)
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Open AccessReview Bioactivity, Health Benefits, and Related Molecular Mechanisms of Curcumin: Current Progress, Challenges, and Perspectives
Nutrients 2018, 10(10), 1553; https://doi.org/10.3390/nu10101553
Received: 27 August 2018 / Revised: 8 October 2018 / Accepted: 16 October 2018 / Published: 19 October 2018
Cited by 1 | PDF Full-text (1797 KB) | HTML Full-text | XML Full-text
Abstract
Curcumin is a principal curcuminoid of turmeric (Curcuma longa), which is commonly used as a spice in cooking and a yellow pigment in the food processing industry. Recent studies have demonstrated that curcumin has a variety of biological activities and pharmacological [...] Read more.
Curcumin is a principal curcuminoid of turmeric (Curcuma longa), which is commonly used as a spice in cooking and a yellow pigment in the food processing industry. Recent studies have demonstrated that curcumin has a variety of biological activities and pharmacological performances, providing protection and promotion of human health. In addition to presenting an overview of the gut metabolism of curcumin, this paper reviews the current research progress on its versatile bioactivity, such as antioxidant, anti-inflammatory, and immune-regulatory activities, and also intensively discusses its health benefits, including the protective or preventive effects on cancers and diabetes, as well as the liver, nervous system, and cardiovascular systems, highlighting the potential molecular mechanisms. Besides, the beneficial effects of curcumin on human are further stated based on clinical trials. Considering that there is still a debate on the beneficial effects of curcumin, we also discuss related challenges and prospects. Overall, curcumin is a promising ingredient of novel functional foods, with protective efficacy in preventing certain diseases. We hope this comprehensive and updated review will be helpful for promoting human-based studies to facilitate its use in human health and diseases in the future. Full article
(This article belongs to the Special Issue Phytochemicals in Health and Disease)
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Open AccessReview Chemical Composition and Biological Activities of Essential Oils of Curcuma Species
Nutrients 2018, 10(9), 1196; https://doi.org/10.3390/nu10091196
Received: 4 August 2018 / Revised: 27 August 2018 / Accepted: 28 August 2018 / Published: 1 September 2018
Cited by 2 | PDF Full-text (774 KB) | HTML Full-text | XML Full-text
Abstract
Members of the genus Curcuma L. have been used in traditional medicine for centuries for treating gastrointestinal disorders, pain, inflammatory conditions, wounds, and for cancer prevention and antiaging, among others. Many of the biological activities of Curcuma species can be attributed to nonvolatile [...] Read more.
Members of the genus Curcuma L. have been used in traditional medicine for centuries for treating gastrointestinal disorders, pain, inflammatory conditions, wounds, and for cancer prevention and antiaging, among others. Many of the biological activities of Curcuma species can be attributed to nonvolatile curcuminoids, but these plants also produce volatile chemicals. Essential oils, in general, have shown numerous beneficial effects for health maintenance and treatment of diseases. Essential oils from Curcuma spp., particularly C. longa, have demonstrated various health-related biological activities and several essential oil companies have recently marketed Curcuma oils. This review summarizes the volatile components of various Curcuma species, the biological activities of Curcuma essential oils, and potential safety concerns of Curcuma essential oils and their components. Full article
(This article belongs to the Special Issue Phytochemicals in Health and Disease)
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Open AccessReview Anti-Cancer Natural Products and Their Bioactive Compounds Inducing ER Stress-Mediated Apoptosis: A Review
Nutrients 2018, 10(8), 1021; https://doi.org/10.3390/nu10081021
Received: 25 June 2018 / Revised: 23 July 2018 / Accepted: 1 August 2018 / Published: 4 August 2018
Cited by 4 | PDF Full-text (1258 KB) | HTML Full-text | XML Full-text
Abstract
Cancer is the second biggest cause of death worldwide. Despite a number of studies being conducted, the effective mechanism for treating cancer has not yet been fully understood. The tumor-microenvironment such as hypoxia, low nutrients could disturb function of endoplasmic reticulum (ER) to [...] Read more.
Cancer is the second biggest cause of death worldwide. Despite a number of studies being conducted, the effective mechanism for treating cancer has not yet been fully understood. The tumor-microenvironment such as hypoxia, low nutrients could disturb function of endoplasmic reticulum (ER) to maintain cellular homeostasis, ultimately leading to the accumulation of unfolded proteins in ER, so-called ER stress. The ER stress has a close relation with cancer. ER stress initiates unfolded protein response (UPR) to re-establish ER homeostasis as an adaptive pathway in cancer. However, persistent ER stress triggers the apoptotic pathway. Therefore, blocking the adaptive pathway of ER stress or facilitating the apoptotic pathway could be an anti-cancer strategy. Recently, natural products and their derivatives have been reported to have anti-cancer effects via ER stress. Here, we address mechanisms of ER stress-mediated apoptosis and highlight strategies for cancer therapy by utilizing ER stress. Furthermore, we summarize anti-cancer activity of the natural products via ER stress in six major types of cancers globally (lung, breast, colorectal, gastric, prostate and liver cancer). This review deepens the understanding of ER stress mechanisms in major cancers as well as the suppressive impact of natural products against cancers via ER stress. Full article
(This article belongs to the Special Issue Phytochemicals in Health and Disease)
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