PMID: 

Food Funct. 2019 Nov 1 ;10(11):7103-7120. Epub 2019 Oct 17. PMID: 31621765

Abstract Title: 

Isolation of strawberry anthocyanin-rich fractions and their mechanisms of action against murine breast cancer cell lines.

Abstract: 

The aim of this study was the evaluation of the effects of strawberry anthocyanin extract treatment on two in vitro models of murine breast cancer cell lines, in an attempt to detect a specific pathway (AMP-activated protein kinase or AMPK) through which strawberries exert their anticancer activity. The anticancer activity of purified anthocyanin extracts from an Alba cultivar on two murine cancer cell lines, N202/1A (with high levels of the HER2/neu oncogene) and N202/1E (with low levels of the HER2/neu oncogene), was evaluated after 48 and 72 h of treatment. The cell viability and apoptosis, intracellular ROS rates, and cell oxidative damage were assessed. Western blot assays were performed to analyze the expression of several proteins related to apoptosis, autophagy, metastasis, the oxidative status, mitochondrial functionality, and the AMPK pathway. This study demonstrated that the anthocyanin extract of Alba strawberry shows an antiproliferative effect on cancer cells, through the induction of apoptosis and oxidative stress, by stimulating different molecular pathways. This study is one of the first studies that have tried to deepen the understanding of a candidate pathway for the explanation of the effects of strawberry on cancer cells. A relationship between the AMPK pathway and the anticancer effects of strawberries was demonstrated.

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PMID: 

Food Funct. 2020 Jan 9. Epub 2020 Jan 9. PMID: 31915782

Abstract Title: 

Strawberry (Fragaria× ananassa cv. Romina) methanolic extract promotes browning in 3T3-L1 cells.

Abstract: 

In recent years, the conversion of white adipocytes to brown-like adipocytes by pharmacological and dietary compounds has gained attention as an effective strategy to fight obesity. Strawberry bioactive compounds present several biological activities including antioxidant, anti-inflammatory, anti-cancer, anti-atherosclerotic and antiadipogenic properties. However, to the best of our knowledge, the possible role of strawberry bioactive compounds in white adipose tissue (WAT) browning has never been explored. Our results demonstrated that a strawberry methanolic extract (SE) significantly reduced 3T3-L1 pre-adipocytes differentiation, and down-regulated the mRNA expression of the adipogenic transcription factors CCAAT/enhancer-binding protein (C/REB-α) and peroxisome proliferation-activated receptor (PPAR-γ). It also down-regulated the mRNA expression of resistin and angiotensinogen, two genes considered as markers of white adipocytes, while increased the mRNA expression of pyruvate dehydrogenase lipoamide kinase isozyme 4 (PDK4) and uncoupling protein 1 (UCP1) which, conversely, are brown adipocyte-specific markers. Likewise, SE stimulated AMP-activated protein kinase (AMPKα), sirtuin 1 (Sirt1) and the peroxisome proliferator activated receptor gamma coactivator 1-alpha (PGC-1α), suggesting a possible increase in mitochondrial biogenesis. It also stimulated oxygen consumption rate and uncoupled respiration. Taken together, all these results suggest that SE induces brown fat-like phenotype in 3T3-L1 cells and may have potential therapeutic implications for treatment and/or prevention of obesity.

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PMID: 

Oxid Med Cell Longev. 2019 ;2019:3457846. Epub 2019 Feb 18. PMID: 30911345

Abstract Title: 

Indicaxanthin from(L. Mill) Inhibits Oxidized LDL-Mediated Human Endothelial Cell Dysfunction through Inhibition of NF-B Activation.

Abstract: 

Oxidized low-density lipoproteins (oxLDL) play a pivotal role in the etiopathogenesis of atherosclerosis through the activation of inflammatory signaling events eventually leading to endothelial dysfunction and senescence. In the present work, we investigated the effects of indicaxanthin, a bioavailable, redox-modulating phytochemical fromfruits, with anti-inflammatory activity, against oxLDL-induced endothelial dysfunction. Human umbilical vein cord cells (HUVEC) were stimulated with human oxLDL, and the effects of indicaxanthin were evaluated in a range between 5 and 20M, consistent with its plasma level after a fruit meal (7M). Pretreatment with indicaxanthin significantly and concentration-dependently inhibited oxLDL-induced cytotoxicity; ICAM-1, VCAM-1, and ELAM-1 increase; and ABC-A1 decrease of both protein and mRNA levels. From a mechanistic perspective, we also provided evidence that the protective effects of indicaxanthin were redox-dependent and related to the pigment efficacy to inhibit NF-B transcriptional activity. In conclusion, here we demonstrate indicaxanthin as a novel, dietary phytochemical, able to exert significant protective vascular effects, at nutritionally relevant concentrations.

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PMID: 

Chem Biol Interact. 2019 Sep 1 ;310:108734. Epub 2019 Jul 2. PMID: 31276661

Abstract Title: 

Isorhamnetin glycoside isolated from Opuntia ficus-indica (L.) MilI induces apoptosis in human colon cancer cells through mitochondrial damage.

Abstract: 

This work aimed to evaluate the mechanisms involved in the apoptosis induction of isorhamnetin-3-O-glucosyl-pentoside (IGP) in metastatic human colon cancer cells (HT-29). To achieve this, we assessed phosphatidylserine (PS) exposure, cell membrane disruption, chromatin condensation, cell cycle alterations, mitochondrial damage, ROS production, and caspase-dependence on cell death. Our results showed that IGP induced cell death on HT-29 cells through PS exposure (48%) and membrane permeabilization (30%) as well as nuclear condensation (54%) compared with control cells. Moreover, IGP treatment induced cell cycle arrest in G2/M phase. Bax/Bcl-2 ratio increased and the loss of mitochondrial membrane potential (63%) was observed inIGP-treated cells. Finally, as apoptosis is a caspase-dependent cell death mechanism, we used a pancaspase-inhibitor (Q-VD-OPh) to demonstrate that the cell death induced by IGP was caspase-dependent. Overall these results indicated that IGP induced apoptosis through caspase-dependent mitochondrialdamage in HT-29 colon cancer cells.

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PMID: 

Nat Prod Res. 2019 Nov 12:1-5. Epub 2019 Nov 12. PMID: 31711321

Abstract Title: 

Isolation and characterization of opuntiol from(L. Mill) and its antiproliferative effect in KB oral carcinoma cells.

Abstract: 

In this study, we isolated and characterized a novel bioactive flavonol from the cactus pad ofIndica (L. Mill) (OFI) by chromatography techniques. The isolated compound was characterized by FT-IR,H andC NMR spectroscopy. Single-crystal XRD results illustrate that the obtained flavonol was opuntiol (6-hydroxymethyl-4-methoxy-2-pyran-2-one) and it was found to be near planar except for the H atoms of the methylene and methyl groups. The crystal packing was stabilized by C-H….O and O-H….O intermolecular hydrogen bonds. The isolated opuntiol significantly inhibited KB cells proliferation and its ICvalue was found to be 30 µM. Further, we noticed that opuntiol significantly induced ROS generation and subsequently altered MMP in KB cells. Western blot analysis and morphological observations by fluorescence microscope indicate the apoptotic inducing potential of opuntiol in KB cells.

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PMID: 

Oxid Med Cell Longev. 2019 ;2019:1568720. Epub 2019 Nov 15. PMID: 31827668

Abstract Title: 

Effectiveness ofL.Seed Oil in the Protection and the Healing of Experimentally Induced Gastric Mucosa Ulcer.

Abstract: 

Gastric ulcer is a painful lesion of the gastric mucosa which can be disabling, or even more very serious in the case of a perforation of the stomach and internal hemorrhage. Traditional pharmacopeias have shown the efficacy of various plant extracts in the treatment of this pathology. Some extracts from(OFI) have been proven to have medicinal therapeutic benefits. The aim of this study was to investigate the preventive and curative effects of OFI seed oil extracted by cold pressing on an ethanol-induced gastric ulcer model in rats. Gastroprotective activities of the oil were assessed as pretreatments prior to ethanol gavage of Wistar rats compared to reference drugs. Two oil dose effects were tested. Ulcer and gastric parameters were measured (ulcerated areas (mm), % of ulcer inhibition, gastric juice volume and pH, and mucus weight). Macroscopical and microscopical assessments of the stomachs as well as gastric biopsy histological studies were carried out. OFI oil exhibited a high efficiency in the protection of the cytoarchitecture and function of the gastric mucosa against the severe damages provoked by ethanol intake. Ulcerated areas were very significantly reduced and the % of ulcer inhibition was the highest under OFI oil pretreatment. Mucus production was stimulated, gastric juice volume was reduced, and its pH was increased. Histopathological examination of H&E-stained biopsies collected from gastric mucosae from the different experimental groups confirmed the gastroprotective efficacy of OFI oil against ethanol-induced symptoms such as inflammation and damages like bleeding, erosions, lesions, necrosis, and ulcers. Furthermore, OFI oil treatment speeded-up the reduction of the surface of ethanol-induced ulcerated areas in a dose-dependent manner, leading to a time gain in the healing process. The healing rate reached 91% on day 2 and 99% on day 3, and a complete heal was attained at the fourth day under OFI oil treatment, while ulcer areas were still partially unhealed in all the other groups. The therapeutic effects of OFI oil against gastric ulcer could be mediated by its varied bioactive compounds that we have demonstrated in the analytical study. They could act synergistically or in a delayed manner to optimize the healing process through protective antioxidant properties, as well as an antagonism against histamine H-receptors, a stimulation of the signaling pathways necessary for mucus and bicarbonate production, and reduction of inflammatory processes in the gastric mucosa. Additionally, OFI oil fatty acids (especially unsaturated) and triacylglycerols contribute to the reconstruction and the repair of the cell membrane lipid bilayer during the gastric ulcer healing process.

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PMID: 

Mol Nutr Food Res. 2019 Apr 29:e1801347. Epub 2019 Apr 29. PMID: 31034714

Abstract Title: 

Pear Extract and Malaxinic Acid Reverse Obesity, Adipose Tissue Inflammation, and Hepatosteatosis in Mice.

Abstract: 

SCOPE: Obesity and diabetes are major public health problems and are emerging as pandemics. Considerable evidence suggests that pear fruit consumption is associated with a lower risk of obesity-related complications. Thus, the present study is conducted to investigate the therapeutic potential of pear extract (PE) for reversing obesity and associated metabolic complications in high-fat diet-induced obese mice.METHODS AND RESULTS: Obesity is induced in male C57BL/6 mice fed a high-fat diet for 11 weeks. After the first 6 weeks on the diet, obese mice are administered vehicle or PE for 5 weeks. PE treatment decreases body weight gain, expands white adipose tissue (WAT), and causes hepatic steatosis in obese mice, as well as inhibits adipogenesis and lipogenesis. Impaired glucose tolerance and insulin resistance are improved by PE. In addition, PE reduces macrophage infiltration and expression of pro-inflammatory genes and deactivates mitogen-activated protein kinases in WAT. Finally, malaxinic acid is identified as an active component responsible for the anti-obesity effects of PE in mice.CONCLUSION: The results demonstrate that PE supplementation ameliorates diet-induced obesity and associated metabolic complications and suggest the health-beneficial effects of both pear fruits and malaxinic acid in counteracting these diseases.

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PMID: 

J Integr Med. 2020 Jan ;18(1):59-67. Epub 2019 Dec 6. PMID: 31874814

Abstract Title: 

Effects of Citrullus colocynthis L. in a rat model of diabetic neuropathy.

Abstract: 

OBJECTIVE: This study investigated the biochemical, histopathological and physiological effects of Citrullus colocynthis on peripheral neuropathy in rats with streptozotocin (STZ)-induced diabetes.METHODS: Seventy adult male Sprague-Dawley rats were included in the present study. Diabetes was induced in 60 rats, with a single intraperitoneal injection of STZ (65 mg/kg). After 4 weeks, the diabetic rats were assessed for neuropathy. Then, the diabetic rats with neuropathy were randomly divided into 6 groups for a 4-week treatment with gabapentin, oral administration of C. colocynthis fruit pulp powder (100 and 300 mg/kg per day), topical preparations asoil-based solution and ointment, or placebo. Changes in metabolic, physiological, biochemical and histological parameters were considered as treatment outcomes.RESULTS: Metabolic outcomes (body weight and blood glucose level) were improved in the C. colocynthis-treated groups as compared to placebo. Tail-flick and hot-plate tests also had lower latency in the C. colocynthis-treated groups. Measurement of oxidative stress markers (malondialdehyde, superoxide dismutase and catalase) showed the antioxidant effect of C. colocynthis. Histological evaluation of the sciatic nerve showed that C. colocynthis decreased the number of demyelinated and degenerated nerve fibers. Among the C. colocynthis-treated groups, the one receiving 100 mg/kg power per day orally had the best treatment outcomes.CONCLUSION: The present study showed that C. colocynthis fruit, through its antioxidant and hypoglycemic activities, has a positive effect in the treatment of diabetic neuropathy.

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PMID: 

Br J Nutr. 2014 Jan 28 ;111(2):353-62. Epub 2013 Jul 19. PMID: 23866068

Abstract Title: 

Fruit and vegetable intake and risk of CHD: results from prospective cohort studies of Chinese adults in Shanghai.

Abstract: 

The protective effects of fruits and vegetables against CHD have been suggested by many epidemiological studies among Western populations. However, prospective data are lacking for Asian populations. In the present study, we examined the associations of fruit and vegetable intake with CHD incidence among 67 211 women (aged 40-70 years) and 55 474 men (aged 40-74 years) living in Shanghai, China. Food intake was assessed using validated FFQ through in-person interviews. Coronary events (non-fatal myocardial infarction or fatal CHD) were identified by biennial home visits and further confirmed by medical record review. During a mean follow-up period of 9·8 and 5·4 years, 148 events in women and 217 events in men were documented and verified. After adjustment for potential confounders, women in the highest quartile of total fruit and vegetable intake (median 814 g/d) had a hazard ratio (HR) of0·62 (95 % CI 0·38, 1·02) for CHD (P for trend = 0·04) compared with those in the lowest quartile (median 274 g/d). This association was primarily driven by fruits (HR for the highest v. the lowest intake in women: 0·62, 95 % CI 0·37, 1·03). The strength of the association was attenuated after further controlling for history of diabetes or hypertension. For men, no significant association was found for fruit and vegetable intake when analysed either in combination or individually. The present findings suggest that a high consumption of fruits may reduce CHD risk in Chinese women.

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PMID: 

Inflammation. 2019 Nov 18. Epub 2019 Nov 18. PMID: 31741196

Abstract Title: 

Walnut-Associated Fatty Acids Inhibit LPS-Induced Activation of BV-2 Microglia.

Abstract: 

Walnuts have high levels of the omega-3 fatty acid alpha-linolenic acid (C18:3n-3, ALA) and the omega-6 fatty acid linoleic acid (C18:2n-6, LA). Previous research has demonstrated that pre-treatment of BV-2 microglia with walnut extract inhibited lipopolysaccharide (LPS)-induced activation of microglia. As an extension of that study, the effects of walnut-associated fatty acids on BV-2 microglia were assessed. BV-2 murine microglia cells were treated with LA, ALA, or a combination of LA+ALA prior to or after exposure to LPS. Nitric oxide (NO) and tumor necrosis factor-alpha (TNF-alpha) were measured in cell-conditioned media. Cyclooxeganse-2 (COX-2) and inducible nitric oxide synthase (iNOS) expression were assessed in BV-2 microglia. Both LA and ALA protected against LPS-induced increases in NO, iNOS, COX-2, and TNF-alpha when used before LPS exposure. When BV-2 microglia were treated with fatty acids after LPS, only COX-2 and TNF-alpha were significantly attenuated by the fatty acids. There was no synergism of LA+ALA, as the LA+ALA combination was no more effective than LA or ALA alone. Fatty acids, like those found in walnuts, may protect against production of cytotoxic intermediates and cell-signaling molecules from microglia and may prove beneficial for preventing age- or disease-related neurodegeneration.

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