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1.
RNA-seq, de novo transcriptome assembly and flavonoid gene analysis in 13 wild and cultivated berry fruit species with high content of phenolics.
Thole, V, Bassard, JE, Ramírez-González, R, Trick, M, Ghasemi Afshar, B, Breitel, D, Hill, L, Foito, A, Shepherd, L, Freitag, S, et al
BMC genomics. 2019;(1):995
Abstract
BACKGROUND Flavonoids are produced in all flowering plants in a wide range of tissues including in berry fruits. These compounds are of considerable interest for their biological activities, health benefits and potential pharmacological applications. However, transcriptomic and genomic resources for wild and cultivated berry fruit species are often limited, despite their value in underpinning the in-depth study of metabolic pathways, fruit ripening as well as in the identification of genotypes rich in bioactive compounds. RESULTS To access the genetic diversity of wild and cultivated berry fruit species that accumulate high levels of phenolic compounds in their fleshy berry(-like) fruits, we selected 13 species from Europe, South America and Asia representing eight genera, seven families and seven orders within three clades of the kingdom Plantae. RNA from either ripe fruits (ten species) or three ripening stages (two species) as well as leaf RNA (one species) were used to construct, assemble and analyse de novo transcriptomes. The transcriptome sequences are deposited in the BacHBerryGEN database (http://jicbio.nbi.ac.uk/berries) and were used, as a proof of concept, via its BLAST portal (http://jicbio.nbi.ac.uk/berries/blast.html) to identify candidate genes involved in the biosynthesis of phenylpropanoid compounds. Genes encoding regulatory proteins of the anthocyanin biosynthetic pathway (MYB and basic helix-loop-helix (bHLH) transcription factors and WD40 repeat proteins) were isolated using the transcriptomic resources of wild blackberry (Rubus genevieri) and cultivated red raspberry (Rubus idaeus cv. Prestige) and were shown to activate anthocyanin synthesis in Nicotiana benthamiana. Expression patterns of candidate flavonoid gene transcripts were also studied across three fruit developmental stages via the BacHBerryEXP gene expression browser (http://www.bachberryexp.com) in R. genevieri and R. idaeus cv. Prestige. CONCLUSIONS We report a transcriptome resource that includes data for a wide range of berry(-like) fruit species that has been developed for gene identification and functional analysis to assist in berry fruit improvement. These resources will enable investigations of metabolic processes in berries beyond the phenylpropanoid biosynthetic pathway analysed in this study. The RNA-seq data will be useful for studies of berry fruit development and to select wild plant species useful for plant breeding purposes.
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2.
Acute Ingestion of a Mixed Flavonoid and Caffeine Supplement Increases Energy Expenditure and Fat Oxidation in Adult Women: A Randomized, Crossover Clinical Trial.
Nieman, DC, Simonson, A, Sakaguchi, CA, Sha, W, Blevins, T, Hattabaugh, J, Kohlmeier, M
Nutrients. 2019;(11)
Abstract
This randomized, double-blinded, crossover study measured the acute effect of ingesting a mixed flavonoid-caffeine (MFC) supplement compared to placebo (PL) on energy expenditure (EE) and fat oxidation (FATox) in a metabolic chamber with premenopausal women (n = 19, mean ± SD, age 30.7 ± 8.0 year, BMI 25.7 ± 3.4 kg/m2). The MFC supplement (658 mg flavonoids, split dose 8:30, 13:00) contained quercetin, green tea catechins, and anthocyanins from bilberry extract, and 214 mg caffeine. Participants were measured twice in a metabolic chamber for a day, four weeks apart, with outcomes including 22 h EE (8:30-6:30), substrate utilization from the respiratory quotient (RQ), plasma caffeine levels (16:00), and genotyping for the single-nucleotide polymorphism (SNP) rs762551. Areas under the curve (AUC) for metabolic data from the MFC and PL trials were calculated using the trapezoid rule, with a mixed linear model (GLM) used to evaluate the overall treatment effect. The 22 h oxygen consumption and EE were significantly higher with MFC than PL (1582 ± 143, 1535 ± 154 kcal/day, respectively, p = 0.003, trial difference of 46.4 ± 57.8 kcal/day). FATox trended higher for MFC when evaluated using GLM (99.2 ± 14.0, 92.4 ± 14.4 g/22 h, p = 0.054). Plasma caffeine levels were significantly higher in the MFC versus PL trial (5031 ± 289, 276 ± 323 ng/mL, respectively, p < 0.001). Trial differences for 22 h EE and plasma caffeine were unrelated after controlling for age and body mass (r = -0.249, p = 0.139), and not different for participants with the homozygous allele 1, A/A, compared to C/A and C/C (p = 0.50 and 0.56, respectively). In conclusion, EE was higher for MFC compared to PL, and similar to effects estimated from previous trials using caffeine alone. A small effect of the MFC on FATox was measured, in contrast to inconsistent findings previously reported for this caffeine dose. The trial variance for 22 h EE was not significantly related to the variance in plasma caffeine levels or CYP1A2*1F allele carriers and non-carriers.
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3.
A randomised double-blind placebo-controlled feasibility trial of flavonoid-rich cocoa for fatigue in people with relapsing and remitting multiple sclerosis.
Coe, S, Cossington, J, Collett, J, Soundy, A, Izadi, H, Ovington, M, Durkin, L, Kirsten, M, Clegg, M, Cavey, A, et al
Journal of neurology, neurosurgery, and psychiatry. 2019;(5):507-513
Abstract
UNLABELLED The impact of flavonoids on fatigue has not been investigated in relapsing and remitting multiple sclerosis (RRMS). OBJECTIVE To determine the feasibility and estimate the potential effect of flavonoid-rich cocoa on fatigue and fatigability in RRMS. METHODS A randomised double-blind placebo-controlled feasibility study in people recently diagnosed with RRMS and fatigue, throughout the Thames Valley, UK (ISRCTN69897291). During a 6-week intervention participants consumed a high or low flavonoid cocoa beverage daily. Fatigue and fatigability were measured at three visits (weeks 0, 3 and 6). Feasibility and fidelity were assessed through recruitment and retention, adherence and a process evaluation. RESULTS 40 people with multiple sclerosis (10 men, 30 women, age 44±10 years) were randomised and allocated to high (n=19) or low (n=21) flavonoid groups and included in analysis. Missing data were <20% and adherence to intervention of allocated individuals was >75%. There was a small effect on fatigue (Neuro-QoL: effect size (ES) 0.04, 95% CI -0.40 to 0.48) and a moderate effect on fatigability (6 min walk test: ES 0.45, 95% CI -0.18 to 1.07). There were seven adverse events (four control, three intervention), only one of which was possibly related and it was resolved. CONCLUSION A flavonoid beverage demonstrates the potential to improve fatigue and fatigability in RRMS.
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4.
Annurca apple polyphenol extract selectively kills MDA-MB-231 cells through ROS generation, sustained JNK activation and cell growth and survival inhibition.
Martino, E, Vuoso, DC, D'Angelo, S, Mele, L, D'Onofrio, N, Porcelli, M, Cacciapuoti, G
Scientific reports. 2019;(1):13045
Abstract
Polyphenols represent the most studied class of nutraceuticals that can be therapeutics for a large spectrum of diseases, including cancer. In this study, we investigated for the first time the antitumor activities of polyphenol extract from Annurca apple (APE) in MDA-MB-231 triple negative breast cancer cells, and we explored the underlying mechanisms. APE selectively inhibited MDA-MB-231 cell viability and caused G2/M phase arrest associated with p27 and phospho-cdc25C upregulation and with p21 downregulation. APE promoted reactive oxygen species (ROS) generation in MDA-MB-231 cells while it acted as antioxidant in non-tumorigenic MCF10A cells. We demonstrated that ROS generation represented the primary step of APE antitumor activity as pretreatment with antioxidant N-acetylcysteine (NAC) prevented APE-induced G2/M phase arrest, apoptosis, and autophagy. APE downregulated Dusp-1 and induced a significant increase in JNK/c-Jun phosphorylation that were both prevented by NAC. Moreover, downregulation of JNK by its specific inhibitor SP600125 significantly diminished the anticancer activity of APE indicating that ROS generation and sustained JNK activation represented the main underlying mechanism of APE-induced cell death. APE also inhibited AKT activation and downregulated several oncoproteins, such as NF-kB, c-myc, and β-catenin. In light of these results, APE may be an attractive candidate for drug development against triple negative breast cancer.
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5.
Ultrasound-Assisted Aqueous Extraction of Phenolic, Flavonoid Compounds and Antioxidant Activity of Mucuna macrocarpa Beans: Response Surface Methodology Optimization.
Aware, CB, Patil, RR, Vyavahare, GD, Gurme, ST, Jadhav, JP
Journal of the American College of Nutrition. 2019;(4):364-372
Abstract
OBJECTIVE This investigation was undertaken to optimize the effective extraction of total phenolics content (TPC), total flavonoids content (TFC), and antioxidant activity from the Mucuna macrocarpa (MM) beans. An ultrasound-assisted extraction (UAE) technique with water as an effective solvent was proposed for the response surface methodology (RSM) optimization. METHODS A three-level, two-factor central composite design (CCD) was employed to reveal the optimal points of variables. Different extraction times (5, 10, 15 minutes) and ultrasonic power levels (10, 20, 30 W) were used for the optimization. The experimental runs given by the RSM were evaluated for TPC, TFC, 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activity (RSA), and N,N-dimethyl-p-phenylenediamine (DMPD) RSA and ferric reducing antioxidant power (FRAP). RESULTS The predicted times for maximum extraction of TPC (186.61 mg GAE g-1), TFC (148.87 mg QUE g-1), and DPPH RSA (99.37%), and DMPD RSA (50.58%) and FRAP (2.38 O.D. at 593 nm) were 12.57, 12.84, 12.43, 12.97, and 13.24 min, and ultrasonic power levels were found to be 27.30, 26.76, 26.22, 27.03, and 27.84 W, respectively. Reverse-phase high-performance liquid chromatography (RP-HPLC) analysis of phenolics compounds from the RSM optimized sample showed tannic acid (48.09 ± 1.92 mg/g), gallic acid (1.17 ± 0.19 mg/g), p-coumaric acid (0.56 ± 0.03 mg/g), and p-hydroxybenzoic acid (0.049 ± 0.01 mg/g) content. CONCLUSION Water and ultrasonication were found to be an effective extraction solvent and technique. RSM was effectively employed to investigate the optimal process conditions for the maximum extraction of TPC, TFC, and antioxidant compounds from the MM beans. Further, MM beans can be explored as a prominent antioxidant source for the treatment of several disorders.
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6.
Chrysin: Pharmacological and therapeutic properties.
Naz, S, Imran, M, Rauf, A, Orhan, IE, Shariati, MA, Iahtisham-Ul-Haq, , IqraYasmin, , Shahbaz, M, Qaisrani, TB, Shah, ZA, et al
Life sciences. 2019;:116797
Abstract
Chrysin is a promising phytochemical that is categorized under the class of flavonoids based on its chemical structure. Naturally, it is widely present in propolis, honey, passion fruit, and even in mushrooms and other plant sources, whereas its synthetic counterparts are also being employed for pharmacological purposes. It has widely been employed in treatment of various degenerative disorders and provides cytotoxic and anti-inflammatory functions. Its antioxidant and disease preventing abilities are attributed to its structural diversity arising in ring-A and absence of oxygenation in B and C ring. In this review, the scientific studies are being reported emphasizing benefits and its allied health claims on chrysin in numerous metabolic malfunctions.
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7.
Bioactive food compounds, epigenetics and chronic disease prevention: Focus on early-life interventions with polyphenols.
Silva, LBAR, Pinheiro-Castro, N, Novaes, GM, Pascoal, GFL, Ong, TP
Food research international (Ottawa, Ont.). 2019;:108646
Abstract
Consumption of bioactive compounds such as polyphenols, isothiocyanates, sulfur-containing compounds and terpenoids, found in fruits and vegetables, is associated with prevention of chronic disease. These bioactive food compounds elicit their protective effects through complex mechanisms at the cellular and molecular, including epigenetic levels. According to the Developmental Origins of Health and Disease (DOHaD) paradigm, in utero exposure to stressors such as malnutrition through maternal diet would impair fetal development and epigenetically program increased risk of metabolic diseases and some cancers in adult life. In addition, a role for fathers´ diet during preconception on their offspring health and chronic disease susceptibility has also emerged. This highlights early life as a promising window of opportunity for starting dietary interventions focusing on preventing chronic diseases. However, knowledge on the potential beneficial impact of early life exposure to bioactive food compounds is limited. Among the studies that have investigated bioactive food compounds in the context of DOHaD, most have focused on the impact of dietary polyphenols. Thus, in this review we discuss experimental evidence supporting a role for the dietary polyphenols resveratrol, genistein, epigallocatechin-3-gallate and anthocyanins in chronic disease prevention considering a perspective from early-life interventions through maternal and paternal diets and focusing on epigenetics as a potential underlying mechanism.
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8.
In vitro and in vivo inhibition of maillard reaction products using amino acids, modified proteins, vitamins, and genistein: A review.
Mazumder, MAR, Hongsprabhas, P, Thottiam Vasudevan, R
Journal of food biochemistry. 2019;(12):e13089
Abstract
Maillard reaction is known to result in loss of nutrients, particularly that of essential amino acids; decrease in digestibility and safety issues due to the development of toxic compounds. Maillard reaction products are also known to cause oxidation of tissues and inflammation, thus increasing the risk of cardiovascular diseases and diabetes. The aim of this review is to present a detailed information about the role of foodborne constituents as antibrowning agents to significantly reduce the harmful compounds like advanced glycation end products (AGEs) during food processing. This review includes strategies involving addition of amino acids, aromatic compounds, vitamins, modification of amino acids, and reducing sugars as antibrowning agents to reduce the AGEs. The role of Food borne functional ingredients such as catechin, epicathechin, luteolin, and ferulic acids as inhibitors of AGEs is also discussed. Among the naturally occurring inhibitors, genistein could be a crucial and safe agent to reduce reactive intermediates. PRACTICAL APPLICATIONS Maillard reaction leads to changes in food color, protein functionality, protein digestibility, and loss of nutrient from foods. Maillard reaction products (MRPs) is also reported to be associated with various inflammatory conditions and may contribute to the progress of chronic diseases, including diabetes. It is hence necessary to reduce the MRPs, in both food and biological products, to offset this phenomenon. Among the strategies adopted till date, chemical agents could inhibit reactive carbonyl species and reactive oxygen species, but also are known to elicit serious side effects. Dietary flavonoids could be a very good inhibitor of MRPs both in biological and in food systems. It could be suggested that dietary flavonoids and isoflavones can be used as antibrowning agents in food and pharmaceutical industries particularly for targeted and sustained release of hypoglycemic drug in the intestines.
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9.
Ultrasound-assisted aqueous extraction of total flavonoids and hydroxytyrosol from olive leaves optimized by response surface methodology.
Yao, Q, Shen, Y, Bu, L, Yang, P, Xu, Z, Guo, X
Preparative biochemistry & biotechnology. 2019;(9):837-845
Abstract
Olive leaves were often extracted with methanol or ethanol at different proportions. In this study, ultrasound-assisted aqueous extraction was adopted for olive leaf extraction. The yields of total flavonoids (TF) and hydroxytyrosol (HT) were optimized by central composite experimental design. Two second-order polynomial equations were established to quantify the relationship between the responses and the processing parameters. Under the optimal condition of extracting at 60 °C for 60 min with the solvent-to-material ratio of 40, TF and HT amounted to 57.31 ± 0.35 and 1.80 ± 0.02 mg/g dry leaves (DL), respectively. The scavenging rate of all extracts against α, α-diphenyl-β-picrylhydrazyl (DPPH) and hydroxyl free radicals was screened. The integrated scores, representing both active ingredients and antioxidant capacity of the extracts, were calculated by principle component analysis (PCA). The optimal extract gained the highest score in PCA. In addition, compared to the extracts from 80% methanol to 44% ethanol, the ultrasound-assisted aqueous extract was richer in TF, HT, and polyphenols, while it also presented stronger ferric reducing antioxidant power (FRAP), but poorer strength to quench hydroxyl radicals. The study indicated that the aqueous extract of olive leaves may present broad potential opportunities in health-care sector.
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10.
Effects of pycnogenol on cardiometabolic health: A systematic review and meta-analysis of randomized controlled trials.
Malekahmadi, M, Moradi Moghaddam, O, Firouzi, S, Daryabeygi-Khotbehsara, R, Shariful Islam, SM, Norouzy, A, Soltani, S
Pharmacological research. 2019;:104472
Abstract
AIM: Clinical trials on the effect of pycnogenol supplementation on cardiometabolic health have been controversial. We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) to evaluate the potential effect of pycnogenol supplementation on cardiometabolic profile. METHODS PubMed, Scopus, and ISI Web of Science databases were searched until October 2018. RCTs that evaluated the effects of pycnogenol on cardiometabolic parameters were included. DerSimonian and Laird random-effect models were used to compute the weighted mean differences (WMDs) and 95% confidence intervals (CIs). RESULTS Twenty-four RCTs including 1594 participants were included in the meta-analysis. Pycnogenol significantly reduced fasting blood glucose (WMD: -5.86 mg/dl; 95% CI: -9.56, -2.15), glycated hemoglobin (WMD = -0.29%, 95%CI: -0.56, -0.01), systolic blood pressure (WMD: -2.54 mmhg; 95% CI: -4.08, -0.99), diastolic blood pressure (WMD: -1.76 mmhg; 95% CI: -3.12, -0.41), body mass index (WMD: -0.47 kg/m2; 95% CI: -0.90, -0.03), LDL cholesterol (WMD: -7.12 mg/dl; 95% CI: -13.66, -0.58) and increased HDL cholesterol (WMD: 3.27 mg/dl; 95% CI: 0.87, 5.66). CONCLUSION This meta-analysis suggests that pycnogenol may have a role in preventing cardiometabolic disease. However, further well-designed RCTs are recommended to evaluate its long-term effects and explore the optimal duration of use and dosage.