PMID: 

Cell Mol Neurobiol. 2019 May 30. Epub 2019 May 30. PMID: 31147852

Abstract Title: 

Pretreatment of Grape Seed Proanthocyanidin Extract Exerts Neuroprotective Effect in Murine Model of Neonatal Hypoxic-ischemic Brain Injury by Its Antiapoptotic Property.

Abstract: 

Grape seed proanthocyanidin extract (GSPE), an active component extracted from the grape, has been reported to demonstrate antioxidant, anti-inflammatory, anticancer, and antiapoptosis effects. However, little is known about the role of GSPE on neonatal hypoxic-ischemic (HI) brain injury. The aim of this study was to evaluate the neuroprotective effect of GSPE pretreatment on neonatal HI brain injury in mice. A modified Rice-Vannucci method was performed to induce neonatal HI brain injury in the 7-day-old mouse pups pretreated with GSPE or vehicle. The infarct volumes were determined by TTC staining. TUNEL staining was used to detect cells apoptosis, and the expressions of apoptosis-related proteins: bax, bcl2, and cleaved caspase-3 were assayed by Western blot. Behavioral tests were also conducted to assess the functional recovery after injury. We showed that the brain damage and neurobehavioral outcomes improvement was observed in GSPE pretreated group. GSPE was proved to suppress apoptosis through inhibition of bax and cleaved caspase-3 expression. It demonstrates that GSPE could alleviate brain damage maybe through its antiapoptotic activity in a neonatal HI brain injury model, and GSPE has the potential to be a new drug for effective prevention of this disorder.

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PMID: 

J Nutr. 2019 Jun 8. Epub 2019 Jun 8. PMID: 31175811

Abstract Title: 

Grape Seed Proanthocyanidin Affects Lipid Metabolism via Changing Gut Microflora and Enhancing Propionate Production in Weaned Pigs.

Abstract: 

BACKGROUND: It is not clear whether dietary grape seed proanthocyanidin (GSP) affects mammalian lipid metabolism via the gut microbiota.OBJECTIVE: The aim of this study was to evaluate the contribution of the gut microbiota to the effect of dietary GSP.METHODS: This study was divided into 3 separate experiments using Duroc × Landrace × Yorkshire pigs (50% male) weaned at day 28 and then fed the same basal diet (NC). In Experiment 1, 90 pigs were fed NC or NC with 250 mg GSP/kg (GSP) or 400 mg betaine/kg [positive control (PC)] for 28 d. In Experiment 2, 30 pigs were fed NC, GSP, or GSP with antibiotics (GSP + Abx) diets for 14 d. In Experiment 3, pigs were fed NC, NC plus 1 g sodium propionate/kg (SP), or NC plus 1 g sodium butyrate/kg (SB) diet for 14 d. Serum biochemical indexes, SCFA concentrations, and microbial composition were determined.RESULTS: In Experiment 1, compared with the GSP group, visceral adipocyte area was higher in the NC (28.6%) and PC (18.2%) groups (P ≤ 0.05). Colonic propionate and butyrate concentrations were 30.2% and 3.6% higher in the GSP group than in the NC group, respectively (P ≤ 0.05). In Experiment 2, compared with the GSP group, the NC group had a 108% higher Firmicutes to Bacteroidetes ratio and had 50.4%, 61.2%, and 82.3% lower abundance of Akkermansia, Alistipes, and Bacteroides, respectively (P ≤ 0.05); antibiotics removed these effects of GSP. In Experiment 3, serum peptide YY was 19.5% higher in the SP group than in the NC group (P ≤ 0.05), and it did not differ between the SB and NC groups (P > 0.05).CONCLUSIONS: GSP affected lipid metabolism in weaned pigs, which is associated with changed gut microbiota and enhanced microbial propionate production. These findings provide potential mechanisms for GSP intake to improve lipid metabolism.

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PMID: 

Bioorg Med Chem Lett. 2019 Jul 23. Epub 2019 Jul 23. PMID: 31371134

Abstract Title: 

Inhibition ofβ-amyloid-induced neurotoxicity by planar analogues of procyanidin B3.

Abstract: 

Reactive oxygen species (ROS) are known to be produced during the amyloid beta (Aβ) aggregation process. Both ROS production and Aβ fibril formation can result in nerve cell injury. Proanthocyanidins are oligomers of catechin that can act as inhibitors of Aβ aggregation. Procyanidin B3 (Cat-Cat), the dimer of (+)-catechin, can easily cross the blood-brain barrier. Previously,we synthesized two derivatives of Cat-Cat, namely Cat-PCat and PCat-PCat, in which the geometry of one or both catechin molecules in Cat-Cat was constrained to be planar. The antioxidative activities of Cat-PCat and PCat-PCat were found to be stronger than that of Cat-Cat, with PCat-PC at exhibiting the most potent activity. These compounds are predicted to protect against Aβ-induced neurotoxicity via inhibition of Aβ aggregation as well as by antioxidative effects toward Aβ-induced intracellular ROS generation. PCat-PCat exhibited the most potent neuroprotective effects against Aβ-induced cytotoxicity, which resulted from inhibition of β-sheet structure formation during the Aβ aggregation process. PCat-PCat may be a promising lead compound for the treatment of Alzheimer's disease.

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PMID: 

BMC Chem. 2019 Dec ;13(1):21. Epub 2019 Feb 4. PMID: 31384770

Abstract Title: 

Antitumor effect of proanthocyanidin induced apoptosis in human colorectal cancer (HT-29) cells and its molecular docking studies.

Abstract: 

Proanthocyanidin (PAC) is a promising compound that has displayed its potent antineoplastic properties with a specific intrinsic pathway. This precise us to explore the phyto-preventive effect of PAC against colon cancer (HT-29). The results showed that PAC inhibited the cell growth and GIvalue was found to be 6.25 μM for 24 h exposure, when correlated to the normal cell line does not have toxicity was noticed. The linguistic differences, similarly membrane blebbing, cell shrinkage fragmented nuclear bodies and mitochondrial membrane were observed in AO/EtBr and DAPI staining. The features of regular mechanical apoptotic characterization was analyzed by DNA fragmentation. The cell cycle arrest at G2/M phases was detected using FACS analysis. The early and late apoptotic cells were observed by using Annexin V/PI staining. The ligand-protein interaction and docking studies were performed using Schrodinger's software. The QPLD analysis of docking studies revealed that PAC exhibited better binding affinity of – 5.23, – 5.17 and – 4.43, – 4.47 kcal/mol against BCL-XL, CDK2 and were compared with 5-FU respectively, which significantly reveals the anticancerous activity of Proanthocyanidin compound. Thus, the PAC compound provides future application of therapeutic option in the treatment of colon cancers.

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PMID: 

Antiviral Res. 2011 Dec ;92(3):447-52. Epub 2011 Oct 13. PMID: 22020306

Abstract Title: 

Inhibition of viral RNA synthesis in canine distemper virus infection by proanthocyanidin A2.

Abstract: 

Canine distemper virus (CDV) is a contagious and multisystemic viral disease that affects domestic and wild canines as well as other terrestrial and aquatic carnivores. The disease in dogs is often fatal and no specific antiviral therapy is currently available. In this study, we evaluated the in vitro antiviral activity against CDV of proanthocyanidin A2 (PA2), a phenolic dimer belonging to the class of condensed tannins present in plants. Our results showed that PA2 exerted in vitro antiviral activity against CDV with a higher selectivity index compared to ribavirin, included in our study for the previously tested anti-CDV activity. The time of addition assay led us to observe that PA2 was able to decrease the viral RNA synthesis and to reduce progeny virus liberation, at different times post infection suggesting multiple mechanisms of action including inhibition of viral replicative complex and modulation of the redox milieu. These data suggest that PA2, isolated from the bark of Aesculus hippocastanum, has potential usefulness as an anti-CDV compound inhibiting viral replication.

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PMID: 

Res Vet Sci. 2013 Oct ;95(2):717-24. Epub 2013 May 8. PMID: 23664014

Abstract Title: 

In vitro inhibition of canine distemper virus by flavonoids and phenolic acids: implications of structural differences for antiviral design.

Abstract: 

Infection caused by canine distemper virus (CDV) is a highly contagious disease with high incidence and lethality in the canine population. Antiviral activity of flavonoids quercetin, morin, rutin and hesperidin, and phenolic cinnamic, trans-cinnamic and ferulic acids were evaluated in vitro against the CDV using the time of addition assay to determine which step of the viral replicative cycle was affected. All flavonoids displayed great viral inhibition when they were added at the times 0 (adsorption) and 1h (penetration) of the viral replicative cycle. Both quercetin and hesperidin presented antiviral activity at the time 2h (intracellular). In the other hand, cinnamic acid showed antiviral activity at the times 0 and 2h while trans-cinnamic acid showed antiviral effect at the times -1h (pre-treatment) and 0 h. Ferulic acid inhibited CDV replicative cycle at the times 0 and 1h. Our study revealed promising candidates to be considered in the treatment of CDV. Structural differences among compounds and correlation to their antiviral activity were also explored. Our analysis suggest that these compounds could be useful in order to design new antiviral drugs against CDV as well as other viruses of great meaning in veterinary medicine.

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PMID: 

Evid Based Complement Alternat Med. 2018 ;2018:7092416. Epub 2018 Aug 6. PMID: 30174714

Abstract Title: 

Comparison betweenAntiviral Effect of Mexican Propolis and Three Commercial Flavonoids against Canine Distemper Virus.

Abstract: 

Propolis is a resin that honey bees () produce by mixing wax, exudates collected from tree shoots, pollen, and enzymes. It has been used for its biological properties against pathogenic microorganisms including those of viral origin. In the present study, we demonstrate the antiviral effect of Mexican propolis, as well as of the three commercial flavonoids (quercetin, naringenin, and pinocembrin) present in its composition, in cell cultures infected with Canine Distemper Virus. The treatments were carried out with propolis, flavonoids individually, and a mixture of the three flavonoids at three different times. Antiviral activity was evaluated by the inhibition of the relative expression of the virus nucleoprotein gene (Real-Time qPCR) and by the determination of cellular viability (MTT assay). Propolis applied before infection decreased viral expression (0.72 versus 1.0, 1.65, and 1.75 relative expressions) and correlated with increased cell viability (0.314 versus 0.215, 0.259, and 0.237 absorbance units (AU)). The administration of a flavonoid mixture containing the three commercial flavonoids before infection induces a slight decrease in viral expression (0.93 versus 1, 1.42, and 1.82 relative expressions); however, it does not improve cellular viability (0.255 versus 0.247, 0.282, and 0.245 AU). Quercetin administrated at the same time of infection decreases viral expression (0.90 versus 1.0, 3.25, and 1.02 relative expressions) and improves cellular viability (0.294 versus 0.240, 0.250, and 0.245 AU). Pinocembrin and naringenin individually did not show any antiviral activity at the administration times evaluated in this study. The present work is the firststudy of the effect of propolis in Canine Distemper Virus and demonstrated the antiviral activity of Mexican propolis, in addition to the synergy that exists between the three flavonoids on cell viability and the expression of the nucleoprotein virus gene.

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PMID: 

Clin Exp Hypertens. 2019 ;41(3):292-298. Epub 2018 Aug 17. PMID: 30118326

Abstract Title: 

Therapeutic potentials of propolis and pollen on biochemical changes in reproductive function of L-NAME induced hypertensive male rats.

Abstract: 

BACKGROUND: Hypertension is described as increased blood pressure based on changed hemodynamics and associated with an increased oxidative damage to reproductive function. This work is to determine therapeutic and protective effects of apitherapy products (propolis and pollen) on reproductive functions of L-NAME-induced hypertensive male rats.METHODS: Experimental animals were indiscriminately separated into four groups of seven rats in each group: (I) Control, (II) L-NAME, (III) L-NAME+ propolis and (IV) L-NAME+ pollen. At the end of the experimental applications, the rats were decapitated by anesthesia and biochemical analyzes were performed on the removed testicular tissues.RESULTS: The levels of TOS, NF-κB and MDA in the L-NAME group compared to control have increased (p 

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PMID: 

Life Sci. 2018 Oct 15 ;211:40-50. Epub 2018 Sep 8. PMID: 30205096

Abstract Title: 

Malaysian propolis, metformin and their combination, exert hepatoprotective effect in streptozotocin-induced diabetic rats.

Abstract: 

AIMS: Hepatic oxidative stress and weak antioxidant defence system resulting in hepatic lesion, has been reported in diabetic rats. The present study investigated the possible hepatoprotective effects of Malaysian propolis (MP) in diabetic rats, on the background that MP has been reported to have anti-hyperglycemic, antioxidant and anti-inflammatory effects.MATERIALS AND METHODS: Sprague-Dawley rats were randomly divided into 5 groups, namely: normal control (NC), diabetic control (DC), diabetic on 300 mg/kg b.w. MP, diabetic on 300 mg/kg b.w. metformin, and diabetic on MP and metformin combined therapy. Treatment was done orally for 4 weeks, and NC and DC groups received distilled water as vehicle.KEY FINDINGS: Results showed increased fasting blood glucose and serum markers of hepatic lesion (aspartate aminotransferase, alkaline phosphatase, alanine aminotransferase and gamma-glutamyl transferase), increased hepatic lactate dehydrogenase activity, decreased hepatic superoxide dismutase, catalase, glutathione peroxidase, glutathione-S-transferase and glutathione reductase activities, increased immunoexpressions of nuclear factor kappa B, tumor necrosis factor-α, interleukin(IL)-1β and caspase-3, and decreased immunoexpressions of IL-10 and proliferating cell nuclear antigen in the liver of DC group. Histopathology of the liver revealed numerous hepatocytes with pyknotic nuclei and inflammatory infiltration, while periodic acid-schiff staining decreasedin the liver of DC group. Treatment with MP attenuated these negative effects and was comparable to metformin. Furthermore, these effects were better attenuated in the combined therapy-treated diabetic rats.SIGNIFICANCE: Malaysian propolis attenuates hepatic lesion in DM and exerts a synergistic protective effect with the anti-hyperglycemic medication, metformin.

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PMID: 

Eur J Cancer Prev. 2007 Feb ;16(1):71-6. PMID: 17220707

Abstract Title: 

Adverse health indicators correlating with sparsely populated areas in Sweden.

Abstract: 

Earlier studies on health characteristics in Sweden have pointed at a sudden trend change in general health indicators around 1997. The decline was worse in areas with less estimated coverage by the mobile phone system; that is, areas where the average output power from mobile phone handsets is expected to be higher. In this study, health parameters were related to the population density, which is a well defined, rather than an estimated variable. Statistics were obtained from different authorities in Sweden. Data were correlated to the population densities in the 21 different counties of Sweden as well as to estimates of average mobile phone output power. Several health quality measures showed that people in sparsely populated counties in Sweden (as well as in Denmark and Norway) have suffered more illness, and lengthier recovery than people in more densely populated areas since 1997. This is in strong contrast to the situation 20 years ago, when the countryside was the healthiest place in which to live. The indicators strongly correlated with estimated mobile phone area coverage and estimated power output. The indicator statistics suggest that the decline in health in Sweden is not a primary consequence of low population density by itself, but that other factors related to population density are causative. The two factors having the strongest correlation with decreased health quality were the estimated average power output from mobile phones (positive correlation) and the reported coverage from the global system for mobile communication base stations (negative correlation) in each county.

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