PMID: 

J Environ Pathol Toxicol Oncol. 2019 ;38(2):153-163. PMID: 31679278

Abstract Title: 

Rutin Protects against Doxorubicin-Induced Cognitive Dysfunction While Retaining the Anticancer Potential of Dox in a Murine Model of N-Methyl-N-Nitrosourea – Induced Mammary Carcinoma.

Abstract: 

Chemobrain is a significant post-chemotherapy complication for which no approved treatments are available. We had previously identified that rutin inhibits doxorubicin (Dox-) -induced cognitive decline in healthy rats. However, it was important to also establish that it does so in rats with mammary carcinoma without compromising Dox's antitumor potential. Mammary carcinoma was induced in female rats by intraperitonial administration of N-methyl-N-nitrosourea (i.p.). Rats that developed mammary carcinoma were treated with Dox after pretreatment with vehicle or rutin. After Dox exposure (50 days), episodic and spatial memory was assessed using the novel object recognition task and the Morris water maze, respectively. Tumor progression was evaluated by measurement of tumor weight and volume and histological analysis. Blood samples were collected to estimate hematological parameters. Oxidative status and TNF-α levels were estimated in brain homogenates. Dox treatment significantly reduced tumor size and volume. Pretreatment with rutin did not significantly alter Dox's tumor suppression potential, suggesting that it does not influence Dox's anticancer activity. In addition, rutin ameliorated Dox-inducedcognitive decline, myelosuppression, and brain oxidative stress. The present study indicates that rutin protects against Dox-induced cognitive decline and myelosuppression without affecting its antitumor potential.

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PMID: 

Curr Drug Discov Technol. 2019 Nov 5. Epub 2019 Nov 5. PMID: 31692437

Abstract Title: 

Moringa Oleifera in Malnutrition: A Comprehensive Review.

Abstract: 

Nutritional deficiency is a major concern in developing countries resulting in serious health consequences like mental and physical growth retardation. Moringa oleifera(Moringa), a nutritious plantgrowing in tropical regions of developing countries, is a candidate for overcoming nutritional deficiency. Moringa leaves are rich in protein including Sulphur containing amino acids.It contains high amounts of vitamin C than oranges, higher concentration of vitamin A than carrots, higher calcium content than milk and more potassium than bananas. Moreover, there is 9 times more iron in moringa than spinach, 4 times more fiber than oat. This review is enlightening and exploring the nutritional diversification of Moringa oleifera and other benefits which make it a better choice to use in our daily diet to combat the situation of malnutrition.

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PMID: 

Biomolecules. 2019 Nov 5 ;9(11). Epub 2019 Nov 5. PMID: 31694300

Abstract Title: 

Curcumin Ameliorates Lead-Induced Hepatotoxicity by Suppressing Oxidative Stress and Inflammation, and Modulating Akt/GSK-3β Signaling Pathway.

Abstract: 

Lead (Pb) is a toxic heavy metal pollutant with adverse effects on the liver and other body organs. Curcumin (CUR) is the principal curcuminoid of turmeric and possesses strong antioxidant and anti-inflammatory activities. This study explored the protective effect of CUR on Pb hepatotoxicity with an emphasis on oxidative stress, inflammation and Akt/GSK-3β signaling. Rats received lead acetate and CUR and/or ascorbic acid (AA) for seven days and samples were collected for analyses. Pb(II) induced liver injury manifested by elevated serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) and lactate dehydrogenase (LDH), as well as histopathological alterations, including massive hepatocyte degeneration and increased collagen deposition. Lipid peroxidation, nitric oxide, TNF-α and DNA fragmentation were increased, whereas antioxidant defenses were diminished in the liver of Pb(II)-intoxicated rats. Pb(II) increased hepatic NF-κB and JNK phosphorylation and caspase-3 cleavage, whereas Akt and GSK-3β phosphorylation was decreased. CUR and/or AA ameliorated liver function, prevented tissue injury, and suppressed oxidative stress, DNA damage, NF-κB, JNK and caspase-3. In addition, CUR and/or AA activated Akt and inhibited GSK-3β in Pb(II)-induced rats. In conclusion, CUR prevents Pb(II) hepatotoxicity via attenuation of oxidative injury and inflammation, activation of Akt and inhibition of GSK-3β. However, further studies scrutinizing the exact role of Akt/GSK-3β signaling are recommended.

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PMID: 

Front Biosci (Landmark Ed). 2020 Jan 1 ;25:480-497. Epub 2020 Jan 1. PMID: 31585898

Abstract Title: 

Lonicerin prevents inflammation and apoptosis in LPS-induced acute lung injury.

Abstract: 

Acute lung injury (ALI) is a life-threatening condition caused by severe inflammation of lung tissues. We hypothesized that lipopolysaccharide induced acute lung inflammation and injury in mice might be controlled by lonicerin (LCR), a plant flavonoid that impacts immunity, oxidative stress, and cell proliferation. LCR reduced pathological changes including pulmonary edema, elevation of protein in bronchoalveolar lavage, inflammation, pro-inflammatory gene expression, expression of toll-like receptor 4/nuclear factor-kappa B, apoptosis, and significantly reduced mortality. Together, the results suggest that LCR might be a potential and effective candidate for the treatment of ALI that acts by inhibiting inflammation and apoptosis.

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PMID: 

J Appl Toxicol. 2019 01 ;39(1):117-145. Epub 2018 Sep 14. PMID: 30216481

Abstract Title: 

Review of polyphenol-rich products as potential protective and therapeutic factors against cadmium hepatotoxicity.

Abstract: 

Recently, the growing attention of the scientific community has been focused on the threat to health created by environmental pollutants, including toxic metals such as cadmium (Cd), and on the need of finding effective ways to prevent and treat the unfavorable health effects of exposure to them. Particularly promising for Cd, and thus arousing the greatest interest, is the possibility of using various ingredients present in plants, including mainly polyphenolic compounds. As the liver is one of the target organs for this toxic metal and disturbances in the proper functioning of this organ have serious consequences for health, the aim of the present review was to discuss the possibility of using polyphenol-rich food products (e.g., chokeberry, black and green tea, blueberry, olive oil, rosemary and ginger) as the strategy in protection from this xenobiotic hepatotoxicity and treatment of this heavy metal-induced liver damage. Owing to the ability of polyphenols to bind ions of Cd and the strong antioxidative potential of these compounds, as well as their abundance in dietary products, it seems to be of high importance to consider the possibility of using polyphenols as potential preventive and therapeutic agents against Cd hepatotoxicity, determined by its strong pro-oxidative properties. Although most of the data on the effectiveness of polyphenols comes from studies in animals, the fact that some of them are derived from experimental models that reflect human exposure to this metal allows us to assume that some polyphenol-rich food products may be promising protective agents against Cd hepatotoxicity in humans.

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PMID: 

J Med Food. 2019 Oct ;22(10):1032-1040. Epub 2019 May 22. PMID: 31120380

Abstract Title: 

Anti-Inflammatory Action of Blueberry Polyphenols in HIG-82 Rabbit Synoviocytes.

Abstract: 

Rheumatoid arthritis (RA) is an autoimmune and chronic inflammatory disease resulting in joint destruction and disability in the adult population. The etiology of RA is not well understood and presently there is no known cure for this disease. The accumulation and proliferation of fibroblast-like synoviocytes may be involved in cartilage destruction. Bothandstudies support an anti-inflammatory role of dietary polyphenols, the bioactive constituents found in fruits and vegetables. The objective of this study was to investigate the anti-inflammatory role of blueberry polyphenols (BBPs) using rabbit synoviocytes stimulated with tumor necrosis factor alpha (TNF). Rabbit synoviocytes (HIG-82) were treated with varying doses of BBPs and stimulated with TNF. Stimulation of rabbit synoviocytes with the proinflammatory cytokine TNFincreased cell proliferation by∼19% compared with the nonstimulated control. Cell proliferation was significantly decreased in a dose-dependent manner by the treatment with BBPs. Post-TNFstimulation, cells treated with BBPs resulted in decreases in interleukin 1 beta and nuclear factor kappa B (NFB) concentration. Reverse transcription-polymerase chain reaction analysis showed that matrix metalloproteinase 3 increased fivefold in the control TNF-stimulated group, but was decreased by threefold in the blueberry treatment group. These results suggest that downregulation of proinflammatory cytokines and transcription factor NFB by naturally occurring bioactives such as BBPs may be a potential therapeutic strategy for reducing inflammation associated with RA.

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PMID: 

J Pharmacol Sci. 2019 Sep 28. Epub 2019 Sep 28. PMID: 31640920

Abstract Title: 

Puerarin prevents progression of experimental hypoxia-induced pulmonary hypertension via inhibition of autophagy.

Abstract: 

Pulmonary arterial hypertension (PAH) is defined as elevation of mean pulmonary arterial pressure to≥25 mmHg within the low pressure pulmonary circulatory system. PAH is characterized by obstructive vascular remodeling, partially due to excessive pulmonary arterial smooth muscle cell (PASMC) proliferation. Puerarin is a natural flavonoid isolated from the herb Radix puerariae, which has been widely used for the treatment of cardiovascular and cerebrovascular disorders and diabetes. However, how puerarin mediates autophagy in the progression of pulmonary vascular remodeling is unclear. In this study, we explored the effects of puerarin in a hypoxic pulmonary hypertension (PH) rat model using immunohistochemistry, and morphometric analyses of right ventricle. In addition, cell counting kit 8 assay, western blotting and flow cytometry were employed to test cell proliferation in PASMCs, and then autophagy was tested with mRFP-GFP-LC3 fluorescence microscopy and Western blot. We found that puerarin could alleviate hypoxia-induced PH in rats and improved pulmonary histopathology, and also reduced the expression of autophagy markers in vivo and in vitro. Moreover, puerarin also ameliorated hypoxia-induced PASMC proliferation in an autophagy-dependent manner. Overall, these findingsdemonstrated that puerarin could prevent hypoxia-induced PH in rats, possibly via reducing autophagy and suppressing cell proliferation.

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PMID: 

Food Chem. 2017 Jul 15 ;227:305-314. Epub 2017 Jan 18. PMID: 28274436

Abstract Title: 

Red raspberry (Rubus idaeus L.) intake decreases oxidative stress in obese diabetic (db/db) mice.

Abstract: 

Red raspberry fruit intake was investigated on obese diabetic (db/db) mice for 8weeks. Animals fed isocaloric diets (5.3% freeze-dried raspberry, or control) were assessed for obesity-diabetes-disease risk biomarkers. Results showed that raspberry intake improved antioxidant status and lessened plasma interleukin (IL)-6 (0.3-fold of control, p0.05). Plasma levels of total cholesterol (T-CHL), low density lipoprotein-cholesterol (LDL-CHL), and resistin were higher in the raspberry group. Overall, the enhanced detoxifying cell defenses exerted by raspberry intake might be due to its polyphenolics and fibre. This study demonstrates in vivo that raspberry intake, at a dose that can be achieved by human consumption, might protect against diabetes-induced oxidative stress.

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PMID: 

Blood Adv. 2019 Nov 12 ;3(21):3261-3265. PMID: 31698457

Abstract Title: 

Cranberry A-type proanthocyanidins selectively target acute myeloid leukemia cells.

Abstract: 

Most elderly patients affected with acute myeloid leukemia (AML) will relapse and die of their disease even after achieving complete remission, thus emphasizing the urgent need for new therapeutic approaches with minimum toxicity to normal hematopoietic cells. Cranberry (Vaccinium spp.) extracts have exhibited anticancer and chemopreventive properties that have been mostly attributed to A-type proanthocyanidin (A-PAC) compounds. A-PACs, isolated from a commercially available cranberry extract, were evaluated for their effects on leukemia cell lines, primary AML samples, and normal CD34+ cord blood specimens. Our results indicated potent and specific antileukemia activity in vitro. In addition, the antileukemia activity of A-PACs extended to malignant progenitor and stem cell populations, sparing their normal counterparts. The antileukemia effects of A-PACs were also observed in vivo using patient derived xenografts. Surprisingly, we found that the mechanism of cell death was driven by activation of NF-κB. Overall, our data suggest that A-PACs could be used to improve treatments for AML by targeting leukemia stem cells through a potentially novel pathway.

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PMID: 

J Nutr. 2018 05 1 ;148(5):667-674. PMID: 29897487

Abstract Title: 

Dietary Red Raspberry Reduces Colorectal Inflammation and Carcinogenic Risk in Mice with Dextran Sulfate Sodium-Induced Colitis.

Abstract: 

BACKGROUND: Ulcerative colitis causes recurring intestinal mucosal injury and sustained inflammation, increasing the likelihood of colorectal cancer (CRC) development. Dietary red raspberry (RB) is a rich source of phytonutrients known to have anti-inflammatory activity; however, the role of RB on CRC prevention in chronic colitis has not been examined.OBJECTIVE: This study examined the effects of dietary RB supplementation on inflammation, epithelium repair, and oncogenic signaling in dextran sulfate sodium (DSS)-induced chronic colitis in mice.METHODS: Six-week-old male C57BL/6J mice were fed a control or RB (5% of dry feed weight; n = 12/group) diet for 10 wk. Starting from the fourth week, mice were administered 2 repeated cycles of 1% DSS (7-d DSS treatment plus 14-d recovery) and were monitored daily for disease activity index (DAI) score. Colonic tissues were collected at the end of the study for histochemical, immunohistochemical, and biochemical analysis of inflammation, differentiation and proliferation markers.RESULTS: RB supplementation reduced the DAI score and histologic damage (by 38.9%; P ≤ 0.01), expression of inflammatory mediators (by 20-70%; P ≤ 0.01), infiltration of CD4 T cells (by 50%; P ≤ 0.05), and α4β7 integrin and related adhesion molecules (by 33.3%; P ≤ 0.01). Furthermore, RB supplementation facilitated epithelium repair, as evidenced by enhanced goblet cell density, expression of transcription factors including Kruppel-like factor 4 (Klf4) and Hairy and enhancer of split 1 (Hes1), terminal differentiation markers, mucin 2 (Muc2), and intestinal alkaline phosphatase (by 20-200%; P ≤ 0.01). Conversely, proliferating cell nuclear antigen (by 70%; P ≤ 0.01), β-catenin, and signal transducer and activator of transcription 3 (STAT3) signaling (by 19-33%; P ≤ 0.05) were reduced by RB supplementation. In addition, RB supplementation enhanced p53 stability (by 53%) and reduced oncogenic gene expression (by 50-60%).CONCLUSION: RB supplementation reduced DAI score and the risk of CRC development during recurring colitis in mice, suggesting that RB is a possible dietary supplement for patients with ulcerative colitis and related gut inflammatory diseases.

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