PMID: 

Food Chem. 2018 Dec 15 ;269:618-627. Epub 2018 Jul 3. PMID: 30100480

Abstract Title: 

Antioxidant and antidiabetic activity of blackberry after gastrointestinal digestion and human gut microbiota fermentation.

Abstract: 

Blackberry fruit contains high levels of polyphenols particularly anthocyanins which contribute to its biological activities. Bioavailability of polyphenols especially anthocyanins is generally low, it has been proposed that metabolites from polyphenol biotransformation under colonic fermentation are components that exert health benefits. In this study, blackberry was subjected to simulated gastrointestinal digestion and gut microbiota fermentation at different time intervals (0-48 h) to study the changes in bioactive components, its antioxidant and antidiabetic activities. Phenolic compounds, during digestion and fermentation were also analysed. Gut metabolites of blackberry significantly increased the glucose consumption and glycogen content in HepG2 cells. Furthermore, gut metabolites ameliorated high glucose plus palmitic acid-induced ROS overproduction, mitochondrial membrane collapse, and glutathione depletion in HepG2 cells. The mechanism of antidiabetic activity of blackberry was via its potent antioxidant activity. Therefore, our results suggest that blackberry could be recommended as a functional food due to potential antioxidant and antidiabetic activity.

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PMID: 

J Agric Food Chem. 2018 Oct 31 ;66(43):11390-11397. Epub 2018 Oct 22. PMID: 30346163

Abstract Title: 

Neolignans from Red Raspberry ( Rubus idaeus L.) Exhibit Enantioselective Neuroprotective Effects against HO-Induced Oxidative Injury in SH-SY5Y Cells.

Abstract: 

Red raspberry has been well-known for its nutritional purpose. Although this fruit has been reported for its potent antioxidant activity and health-promoting properties, systematic studies responsible for the bioactive constituents were still insufficient. In the current study, three pairs of dihydrobenzofuran-type enantiomeric neolignans (1a/1b-3a/3b), including two new compounds (1b and 2a), were isolated from the fruit of Rubus idaeus. The structures of these enantiomers were determined through spectroscopic methods and quantum mechanical calculations. Biologically, enantiomers 2a and 2b exhibited significant enantioselective protective effects against HO-induced neurotoxicity at 50μM (2a, 86.72 ± 1.17%; 2b, 69.70 ± 1.59%). The underlying mechanism study demonstrated that enantiomer 2a is able to attenuate HO-induced apoptosis, reactive oxygen species (ROS) generation, and mitochondrial dysfunction in SH-SY5Y cells. Overall, these findings provide a valuable foundation for the understanding of neuroprotective activities of red raspberry and further investigation on its potential application values.

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PMID: 

Int J Food Sci Nutr. 2019 Mar 20:1-12. Epub 2019 Mar 20. PMID: 30892114

Abstract Title: 

Effect of blackberry juice (Rubus fruticosus L.) on anxiety-like behaviour in Wistar rats.

Abstract: 

The present study evaluated the effects of blackberry juice that is rich in different concentrations of anthocyanins and polyphenols (2.6 mg/kg anthocyanins, 14.57 mg/kg polyphenols; 5.83 mg/kg anthocyanins, 27.10 mg/kg polyphenols; 10.57 mg/kg anthocyanins, 38.40 mg/kg polyphenols) on anxiety-like behaviour in Wistar rats. The rats were treated with blackberry juice for 21 days and then tested in the elevated plus maze,locomotor activity test and forced swim test. The results were compared with a reference anxiolytic drug diazepam (2.0 mg/kg) and vehicle (8.7 ml/kg). The intermediate dose of blackberry juice exerted an anxiolytic-like effect that was similar to diazepam, without affecting locomotive activity.The low and high doses of blackberry juice exerted no significant effects on anxiety-like behaviour compared with vehicle. In the forced swim test, both the high and intermediate doses of blackberry juice reduced total immobility time, suggesting a protective effect against behavioural changes thatare induced by acute stress. These findings suggest a potential therapeutic effect of blackberry juice on anxiety that is associated with a stressful event.

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PMID: 

Evid Based Complement Alternat Med. 2016 ;2016:5698685. Epub 2016 Dec 22. PMID: 28101119

Abstract Title: 

In Vitro Antiproliferative and Antioxidant Effects of Extracts fromLeaves and Their Quality Evaluation.

Abstract: 

The present study was performed to evaluate the effect of different extracts and subfractions fromleaves on two human colon cancer cell lines obtained from two stages of the disease progression lines HT29 and SW948. Tested samples inhibited the viability of cells, both HT29 and SW948 lines, in a concentration-dependent manner. The most active was the ethyl acetate fraction which, applied at the highest concentration (250 g/mL), decreased the viability of cells (HT29 and SW948) below 66%. The extracts and subfractions were also investigated for antioxidant activities on DPPH and FRAP assays. All extracts, with the exception of water extract at a dose of 250 g/mL, almost totally reduced DPPH. The highest Feion reduction was shown for the diethyl and ethyl acetate fractions. It was more than 6.5 times higher (at a dose 250 g/mL) as compared to the control. The LC-MS studies of the analysed preparations showed that all samples contain a wide variety of polyphenolics, among which ellagitannins turned out to be the main constituents with dominant ellagic acid, sanguiin H-6, and flavonol derivatives.

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PMID: 

Am J Chin Med. 2017 ;45(7):1557-1572. Epub 2017 Sep 25. PMID: 28946771

Abstract Title: 

Rubus idaeus Inhibits Migration and Invasion of Human Nasopharyngeal Carcinoma Cells by Suppression of MMP-2 through Modulation of the ERK1/2 Pathway.

Abstract: 

Nasopharyngeal carcinoma (NPC) is characterized by a high incidence of metastasis in the neck lymph nodes, resulting in a poor prognosis and posing challenges for treatment. In this study, we investigated the in vitro antimetastatic properties of Rubus idaeus extract (RIE) on human nasopharyngeal carcinoma cells. HONE-1, NPC-39 and NPC-BM cells were subjected to RIE treatment, and effects on the migration and invasion of tumor cells were analyzed. The results showed that RIE suppressed the migration and invasion of NPC cells. Gelatin zymography assay, Western blotting and real-time PCR showed that matrix metalloproteinases-2 (MMP-2) enzyme activity, protein expression and mRNA levels were down-regulated by RIE treatment. To identify the signaling pathway, mitogen-activated protein kinase proteins were examined, which showed that phosphorylation of ERK1/2 was inhibited after the treatment of RIE. In summary, our data showed that RIE inhibited the migration and invasion of NPC cells by suppressing the expression of MMP-2 by down-regulating the ERK1/2 signaling pathway, suggesting that Rubus idaeus may serve as chemotherapeutic and chemopreventive agent for NPC.

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PMID: 

Food Chem. 2018 Aug 15 ;257:143-149. Epub 2018 Feb 24. PMID: 29622190

Abstract Title: 

Structural characterization of blackberry wine polysaccharides and immunomodulatory effects on LPS-activated RAW 264.7 macrophages.

Abstract: 

Three polysaccharide fractions were isolated from blackberry wine. The crude extract BWPs was obtained with ethanol precipitation and freeze-thawing process, it was then submitted to Fehling treatment, giving soluble BWPFs and insoluble BWPFp fractions. These fractions were characterized by Gas Chromatography-Mass Spectrometry (GC-MS) and Nuclear Magnetic Resonance (NMR). Major polysaccharides were identified for each fraction: mannan, type II arabinogalactan and type I rhamnogalacturonan for BWPs, a mannan formed by a major chain ofα-Manp(1 → 6)-linked units, O-2 substituted with α-d-Manp(1 → 2)-linked side chains for BWPFp and a AG II formed by a major chain of β-d-Galp(1 → 3)-linked, substituted at O-6 by side chains of the β-d-Galp(1 → 6)-linked, which then are substituted at O-3 by non-reducingunits of α-l-Araf and a RG I, formed by [→4)-α-d-GalpA-(1 → 2)-α-l-Rhap-(1→]for BWPFs. Anti-inflammatory effects of polysaccharide fractions were evaluated in RAW 264.7 cells. Fractions markedly reduced nitric oxide (NO) and pro-inflammatory cytokine production (TNF-α and IL-1β) in LPS-treated cells.

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PMID: 

Molecules. 2018 Aug 21 ;23(9). Epub 2018 Aug 21. PMID: 30134638

Abstract Title: 

Raspberry Polyphenolic Extract Regulates Obesogenic Signals in Hepatocytes.

Abstract: 

The aim of this in vitro study was to examine the effect of raspberry polyphenolic extract on the immune-metabolic molecular mechanisms activated by obesity-related signals in hepatocytes (HB-8965). Alterations in endosomal/lysosomal activity (neutral red uptake assay, NR), the expression of selected genes involved with lipid oxidation, and metabolism and inflammation processes in the liver were studied. Hepatocytes were treated with plasma collected from Wistar rats that were fed a high-fat diet (HF), raspberry polyphenolic extract (PP), serine-type protease inhibitors as an agonist of TLR4 (TD) or a combination of PP with HF or TD treatments. The PP added to the experimental treatments modulated hepatic immune-metabolic mechanisms through the upregulation of STAT1, ANGPTL4, and CD44, as well as considerably reducing the NR uptake and downregulation of COX-2 and the multifunctional protein AhR. The kinetic analysis of AhR expression revealed that HF-related molecular mechanisms activated AhR mRNA expression earlier than PP initiated the regulatory effect. In conclusion, PP might be considered a valuable dietary agent that regulates obesity-related signals in hepatocytes. Moreover, taking AhR kinetic behavior into consideration, it can be assumed that PP might modulate the severity of the HF-induced downstream metabolic signaling of AhR.

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PMID: 

Food Res Int. 2019 Aug ;122:627-634. Epub 2019 Jan 15. PMID: 31229121

Abstract Title: 

Blackberry (Rubus ulmifolius Schott): Chemical composition, phenolic compounds and antioxidant capacity in two edible stages.

Abstract: 

The berries of the genus Rubus has been highlighted as important source of bioactive and health promoting constituents, however, information about chemical composition and antioxidant potential of the specie Rubus ulmifolius are still scarce. In this regard, this study aimed to assess the physicochemical characteristics, total monomeric anthocyanins (TMA), individual phenolics, minerals, sugars, and antioxidant properties of mature and fully mature R. ulmifolius. With the advance of maturation, changes in the physicochemical composition suggest pleasant characteristics for consumption especially in the fully mature stage. High levels of TMA and sugars (fructose and glucose) were also verified in the fully mature stage, as well as, expressive antioxidant potential, with values of 241.06 μM Fe gfor ferric reducing antioxidant power and 28.22 mg gallic acid equivalent gfor Folin-Ciocalteu reducing capacity (all expressed in dry matter, DM). In contrast, minerals (potassium, calcium, sodium) and most of the studied phenolic compounds showed the highest concentrations in mature fruits. Among the phenolics investigated, 26 compounds were identified and quercetin and isoquercitrin were the predominant phenolic compounds in the fruit. The results reinforce the nutritive and antioxidant potential of Rubus ulmifolius in both maturation stages studied.

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PMID: 

Oxid Med Cell Longev. 2019 ;2019:6797921. Epub 2019 Jun 3. PMID: 31281587

Abstract Title: 

Increased Oxidative Stress Induced byBioactive Compounds Induce Apoptotic Cell Death in Human Breast Cancer Cells.

Abstract: 

Bioactive compounds from plants represent good candidate drugs for the prevention and treatment of various forms of cancer. Berries are rich sources of bioactive compounds, and there has been an increasing interest in the study of therapeutic action of wild berries. Oxidants are generated continuously in biological system as a result of physiological process. When there is an imbalance between oxidants and antioxidants, it leads to a condition called oxidative stress. Natural compounds as inducers of oxidative stress are able to modulate the physiological functions of cancer cells leading to cell death or survival. The aim of this study was to evaluate the induction of apoptosis by isolated bioactive compounds (1-(2-hydroxyphenyl)-4-methylpentan-1-one (C1) and 2-[(3-methylbutoxy) carbonyl] benzoic acid (C2)) fromagainst MCF-7 breast cancer cells. The exposure of C1 and C2 reduced viability (ICof C1: 4.69; C2: 8.36 g/mL) and proliferation. Cytochrome c release from mitochondria and changes in mitochondrial membrane potential of treated cells supported the intrinsic apoptotic cell death. Reactive oxygen species (ROS) production after treatment with C1 and C2 was found to be higher and induced nuclear damage. Expression of apoptotic proteins after the treatments was significantly upregulated as indicated using immunofluorescence (caspase 9, p53, and Bax), western blotting (p53, cleaved PARP, cytochrome c, and Bax), and ELISA (caspase 9) analysis. Overall, C1 was more cytotoxic, increased the ROS production in dichlorodihydrofluorescein diacetate assay, and induced apoptosis in breast cancer cells. These results illustrate that berry bioactive compounds have strong chemopreventive potential. In this article, we provide information on prooxidant and anticancer activities ofbioactive compounds. Natural products have always demonstrated a significant contribution to the development of several cancer chemotherapeutic drugs. Most of these compounds are known to affect the redox state of the cell; and studies on these compounds have focused on their antioxidant property instead of prooxidant properties.

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PMID: 

Nutr Neurosci. 2019 Jul 20:1-11. Epub 2019 Jul 20. PMID: 31328696

Abstract Title: 

Red raspberry () supplementation mitigates the effects of a high-fat diet on brain and behavior in mice.

Abstract: 

Research has shown that berries may have the ability to reverse, reduce, or slow the progression of behavioral dysfunction associated with aging and neurodegenerative disease. In contrast, high-energy and high-fat diets (HFD) may result in behavioral deficits like those seen in aging animals. This research examined whether red raspberry () mitigates the effects of HFD on mouse brain and behavior.Eight-week-old mice consumed a HFD (60% calories from fat) or a control diet (CD) with and without 4% freeze-dried red raspberry (RB). Behavioral tests and biochemical assays of brain tissue and serum were conducted.After 12 weeks on the diets, mice fed CD and HFD had impaired novel object recognition, but mice on the RB-supplemented diets did not. After approximately 20 weeks on the diets, mice fed HFD + RB had shorter latencies to find the escape hole in the Barnes maze than the HFD-fed mice. Interleukin (IL)-6 was significantly elevated in the cortex of mice fed HFD; while mice fed the CD, CD + RB, and HFD + RB did not show a similar elevation. There was also evidence of increased brain-derived neurotrophic factor (BDNF) in the brains of mice fed RB diets. This reduction in IL-6 and increase in BDNF may contribute to the preservation of learning and memory in HFD + RB mice.This study demonstrates that RB may protect against the effects HFD has on brain and behavior; however, further research with human subjects is needed to confirm these benefits.

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