PMID: 

PLoS One. 2013 ;8(4):e62026. Epub 2013 Apr 24. PMID: 23637957

Abstract Title: 

Impact of oral typhoid vaccination on the human gut microbiota and correlations with s. Typhi-specific immunological responses.

Abstract: 

The resident microbial consortia of the human gastrointestinal tract play an integral role in modulating immune responses both locally and systemically. However, detailed information regarding the effector immune responses after vaccine administration in relation to the gastrointestinal microbiota is absent. In this study, the licensed oral live-attenuated typhoid vaccine Ty21a was administered in a clinical study to investigate whether oral immunization resulted in alterations of the microbiota and to identify whether a given microbiota composition, or subsets of the community, are associated with defined S. Typhi-specific immunological responses. The fecal microbiota composition and temporal dynamics were characterized using bacterial 16S rRNA pyrosequencing from individuals who were either immunized with the Ty21a typhoid vaccine (n = 13) or served as unvaccinated controls (n = 4). The analysis revealed considerable inter- and intra-individual variability, yet no discernible perturbations of the bacterial assemblage related to vaccine administration were observed. S. Typhi-specific cell mediated immune (CMI) responseswere evaluated by measurement of intracellular cytokine production using multiparametric flow cytometry, and humoral responses were evaluated by measurement of serum anti-LPS IgA and IgG titers. Volunteers were categorized according to the kinetics and magnitude of their responses. While differencesin microbial composition, diversity, or temporal stability were not observed among individuals able to mount a positive humoral response, individuals displaying multiphasic CMI responses harbored more diverse, complex communities. In line with this preliminary observation, over two hundred operational taxonomic units (OTUs) were found to differentiate multiphasic and late CMI responders, the vast majority of which classified within the order Clostridiales. These results provide an unprecedented view into the dramatic temporal heterogeneity of both the gut microbiota and host immune responses.

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PMID: 

Med J Aust. 2011 Sep 19 ;195(6):318-20. PMID: 21929484

Abstract Title: 

Adverse events associated with 2010 CSL and other inactivated influenza vaccines.

Abstract: 

The 2010 trivalent influenza vaccine (TIV) manufactured by CSL Biotherapies (CSL) was associated with increased febrile reactions, including febrile convulsions, among Australian children. CSL is one of the few manufacturers that use deoxycholate as the virus-splitting agent in the manufacture of TIV. Clusters of adverse events following immunisation (AEFI) have been previously linked to other deoxycholate-split TIV formulations in Europe and Canada. We hypothesise that suboptimal virus splitting or other mechanisms related to the use of deoxycholate may have played a role in adverse events linked to the 2010 CSL TIV. This hypothesis garners support from a recent United States Food and Drug Administration warning letter indicating that CSL failed to determine optimal splitting conditions for new virus strains and that assays to assess virus splitting had not been validated. While there may be other causes, the use of deoxycholate should be further explored. Comprehensive and timely investigations of AEFI, especially those involving children, are necessary to prevent their recurrence and to maintain public confidence in vaccination programs.

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PMID: 

J Physiol Pharmacol. 2018 Jun ;69(3). Epub 2018 Aug 22. PMID: 30149369

Abstract Title: 

Oligonol prevented the relapse of dextran sulfate sodium-ulcerative colitis through enhancing NRF2-mediated antioxidative defense mechanism.

Abstract: 

Repeated bouts of ulcerative colitis featured troublesome course of inflammatory bowel disease leading to fatal colitis-associated cancer, which is strongly associated with oxidative stress and sustained inflammation. Since oligonol, low molecular weighted polyphenol extracted from fruit lychee, showed antioxidative and anti-inflammatory actions, we hypothesized that oligonolcan prevent relapse of colitis. We compared oligonol with current gold standard therapeutics, sulfasalazine in preventive efficacy of relapse. First, dextran sulfate sodium (DSS)-induced colitis were made following pretreatment with oligonol, 10, 50, and 100 mg/kg for 7 days to measure therapeutic effect of oligonol and relapse model via repeated DSS administration was made following with either 50 mg/kg oligonol or 30 mg/kg sulfasalazine to explore relapse preventing action of oligonol in C57BL/6 mice. Detailed changes in colon were measured to explain molecular mechanisms. Pretreatment of 10, 50, 100 mg/kg oligonol (p.o.), significantly reduced DSS-induced colitis; total pathologic scores, colon length, and clinical symptom scores (P

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PMID: 

Phytother Res. 2018 Dec ;32(12):2541-2550. Epub 2018 Oct 2. PMID: 30280446

Abstract Title: 

Oligonol, a low-molecular-weight polyphenol derived from lychee peel, attenuates diabetes-induced pancreatic damage by inhibiting inflammatory responses via oxidative stress-dependent mitogen-activated protein kinase/nuclear factor-kappa B signaling.

Abstract: 

This study investigated the effects of oligonol, a low-molecular-polyphenol derived from lychee peel, against diabetes-induced pancreatic damage via oxidative stress-induced inflammation. Oligonol was orally administered at 10 or 20 mg/kg body weight/day for 10 days to streptozotocin-induced diabetic rats, and the rats were compared with nondiabetic and diabetic control rats. The diabetic rats showed loss of body weight and increased pancreatic weight, and the oral administration of oligonol attenuated these parameters. Moreover, the administration of oligonol caused a significant decrease in the serum glucose level and a significant increase in the serum and pancreatic insulin and C-peptide levels in the diabetic rats. Oligonol also significantly reduced the enhanced levels of reactive oxygen species and 2-thiobarbituric acid reactive substance, which are oxidative stress biomarkers, in the serum and pancreas. Oligonol treatment reduced the overexpression of phospho-p38, phospho-ERK1/2, phospho-inhibitor of nuclear factor-kappa B (NF-κB), NF-κBp65, and NF-κBp65-induced inflammatory protein such as cyclooxygenase-2, inducible nitric oxide synthase, tumor necrosis factor-α, and interleukin-6. Furthermore, oligonol treatment led to significantly attenuated histological damage in the pancreas. On the basis of these results, we conclude that a plausible mechanism of oligonol's antidiabetic action may be itsantioxidative stress-related anti-inflammatory action.

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PMID: 

Nutr Cancer. 2019 ;71(1):141-148. Epub 2019 Jan 11. PMID: 30633587

Abstract Title: 

Oligonol, a Low Molecular Weight Polyphenol, Enhances Apoptotic Cell Death in Ovarian Cancer Cells via Suppressing NF-κB Activation.

Abstract: 

BACKGROUND: Oligonol, a low molecular weight polyphenol derived from lychee fruit, not only has anti-inflammatory effects in various disease conditions but also has antitumor-promoting effects. We evaluate the nuclear factor-kappa B (NF-κB)-related anticancer effect of oligonol in ovarian cancer using SKOV-3 cells.METHODS: Cell viability was examined after oligonol treatment using MTT assay and reactive oxygen species (ROS) production measurement. Subsequently, apoptotic cell death was visualized by the TdT-mediated dUTP nick-end labeling (TUNEL) method. The effect of oligonol on the NF-κB signaling pathway was evaluated using western blot analysis and luciferase activity measurement of p65, an NF-κB subunit.RESULTS: Cell viability significantly decreased after oligonol treatment of 72 h. Apoptosis-related markers were highly expressed in oligonol-treated cells, and increased apoptosis after oligonol treatment was also confirmed using the TUNEL assay. Western blotting results showed the expression of NF-κB signaling pathway factors, p-ERK, TRAF2, and p-IκBα, increased following treatment with oligonol, whereas p65 and COX-2 expression decreased. Immunofluorescence imaging results showed p65 luciferase activity in the nucleus as well as a shift to cytoplasmic expression.CONCLUSION: Oligonol treatment significantly enhances apoptotic cell death in SKOV-3 cells, with the suppression of NF-κB activation, which plays an essential role in this anticancer effect.

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PMID: 

Mol Nutr Food Res. 2019 05 ;63(10):e1801102. Epub 2019 Feb 28. PMID: 30793867

Abstract Title: 

Oligonol Alleviates Sarcopenia by Regulation of Signaling Pathways Involved in Protein Turnover and Mitochondrial Quality.

Abstract: 

SCOPE: Oligonol has been shown to moderate mitochondrial biogenesis, protein synthesis, and protein degradation in diabetic mice in a previous study. It is therefore hypothesized that oligonol alleviated sarcopenia by regulating pathways involved in protein turnover and mitochondrial quality.METHODS AND RESULTS: The 32-week-old senescence-accelerated mouse prone 8 (SAMP8) mice are fed with chow diet containing 200 mg kgoligonol for 8 weeks. Oligonol supplementation increased skeletal muscle mass, cross-sectional areas, and grip strength in SAMP8 mice. Oligonol increased phosphorylation of AKT/mTOR/p70sk6, inhibited nuclear localization of FoxO3a and NFκB, and decreased transcription of MuRF-1 and MAFbx in skeletal muscle of SAMP8 mice. Downregulation of mitochondrial biogenesis genes (PGC-1α and Tfam) and mitochondrial fusion genes (Mfn2 and Opa1), loss of PINK1, overexpression of Atg13, LC3-II, and p62, and abundant accumulation of autophagosomes and lysosomes in skeletal muscle of SAMP8 mice are limited by oligonol. Furthermore, oligonol reduced expression of released cytochrome c and cleaved caspase-9 in skeletal muscle of SAMP8 mice.CONCLUSION: Regulating pathways involved in protein synthesis and degradation, mitochondrial biogenesis, mitochondrial fusion/fission, autophagy, and mitochondria-dependent apoptosis by oligonol contribute to positive protein turnover and mitochondrial quality, thus increasing muscle mass and strength in SAMP8 mice.

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PMID: 

Phytomedicine. 2010 Nov ;17(13):1047-56. PMID: 20554190

Abstract Title: 

Oligonol a low molecular weight polyphenol of lychee fruit extract inhibits proliferation of influenza virus by blocking reactive oxygen species-dependent ERK phosphorylation.

Abstract: 

The emergence of resistance to anti-influenza drugs calls for the search for new antiviral molecules with different resistance profiles. Polyphenolic compounds are found in various plants and have antiviral and antioxidative properties. We tested the hypothesis that oligonol, a lychee fruit-derived low molecular weight polyphenol, possesses anti-influenza effects by inhibiting phosphorylation of extracellular-signal-regulated kinases (ERK). Real time PCR, plaque assay, and immunofluorescence techniques were used to study the effects of oligonol on proliferation of influenza virus. Oligonol inhibits influenza virus proliferation by blocking attachment of the virus to MDCK cells and by suppression of nuclear export of influenza virus ribonucleoprotein (RNP). Infection of MDCK cells with influenza virus leads to an increase in production of reactive oxygen species (ROS) and induction of a ROS-dependent ERK phosphorylation. Inhibition of ERK activation by a dominant negative mutant of ERK or N-acetyl-cysteine (NAC) leads to inhibition of influenza RNP nuclear export. Phorbol 12-myristate 13-acetate (PMA) induces ROS production, ERK phosphorylation and enhances influenza proliferation in MDCK cells. Oligonol and NAC inhibit PMA-induced ERK phosphorylation and ROS production. Our studies suggest that the underlying mechanism for the inhibitory effect of oligonol on influenza virus RNP nuclear export is blocking of ROS-dependent induction of ERK phosphorylation.

PMID: 

Avicenna J Phytomed. 2016 Jul-Aug;6(4):458-267. PMID: 27516987

Abstract Title: 

The effect of Allium sativum (Garlic) extract on infectious bronchitis virus in specific pathogen free embryonic egg.

Abstract: 

OBJECTIVE: Garlic is a plant has been used as a flavor, and anti-microbial and anti-diarrheal agent. Infectious bronchitis virus (IBV) is a coronavirus. The available vaccines against IBV cannot cover new variants. This study evaluated the inhibitory effects of garlic extract on IBV.MATERIALS AND METHODS: The constituents of garlic extract were detected by gas chromatography. This study was done in four groups of embryonic SPF eggs; first group was used for virus titration; second group received the mixture of different virus titration and constant amount of garlic extract; third group received 10(-3) titration of virus and after 8 hr received garlic extract and the last group received different dilutions of garlic extract.RESULTS: Based on our results, in the second group, IBV vaccine strain (4/91) at all titration and M41 in 10(-2) and 10(-3) titration and in the third group both variants of virus the embryonic Index (EI) was significantly increased.CONCLUSION: The garlic extract had inhibitory effects on IBV in the chickens embryo.

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PMID: 

Clin Ther. 2000 Feb ;22(2):209-21. PMID: 10743980

Abstract Title: 

Efficacy of oral long-term N-acetylcysteine in chronic bronchopulmonary disease: a meta-analysis of published double-blind, placebo-controlled clinical trials.

Abstract: 

OBJECTIVE: This meta-analysis was performed to assess the possible prophylactic benefit of prolonged treatment with oral N-acetylcysteine (NAC) in chronic bronchitis (CB) based on qualifying clinical trials. Treatment of acute exacerbations with NAC was not investigated.
BACKGROUND: Prolonged treatment with oral NAC has been investigated in a number of studies of patients with CB. NAC prevented acute exacerbations and symptoms of CB in some but not all trials.
METHODS: The trials included in this analysis were selected from a MEDLINE search of the period from January 1, 1980, through June 30, 1995; references in the articles retrieved in the initial search; and consultation with 2 experts. Selection was based on the following criteria: published, double-blind, placebo-controlled, chronic bronchopulmonary disease, duration of therapy>or =2 months, and data sufficient to calculate an outcome variable permitting direct comparison of studies (effect size) for both NAC and placebo groups. The primary end point was the incidence of acute exacerbations in 7 of 8 trials and clinical assessment in the other. In 7 studies, inclusion criteria were based on Medical Research Council criteria for CB, with an additional criterion in some trials. For the meta-analysis, the end points of individual trials were transformed into an effect size as a common outcome.
RESULTS: Of 21 trials initially identified, 8 qualified for inclusion. References from the 8 papers and consultation with the experts produced 8 additional publications, 1 of which qualified for inclusion. NAC was administered orally at a daily dose of 400 mg (1 study), 600 mg (5 studies), or 1200 mg (1 study). One other trial used a dose of 600 mg 3 times per week. The duration of treatment was 3 months (1 study),>or =5 months (2 studies), or 6 months (7 studies). The results of this meta-analysis showed a statistically significant effect size for NAC compared with placebo. The overall value of effect size was -1.37 (95% CI, -1.5 to -1.25). Sensitivity analyses did not significantly alter these results. In a subset analysis of trials with the number of acute exacerbations as a clinical end point, a mean difference of -0.32 clinical event (95% CI, -0.50 to -0.18) was found (ie, a 23% decrease in the number of acute exacerbations compared with placebo).
CONCLUSION: These findings suggest that a prolonged course of oral NAC prevents acute exacerbations of CB, thus possibly decreasing morbidity and health care costs.

PMID: 

Nutrients. 2020 Jan 23 ;12(2). Epub 2020 Jan 23. PMID: 31979305

Abstract Title: 

The Impact of Coconut Oil and Epigallocatechin Gallate on the Levels of IL-6, Anxiety and Disability in Multiple Sclerosis Patients.

Abstract: 

BACKGROUND: Due to the inflammatory nature of multiple sclerosis (MS), interleukin 6 (IL-6) is high in blood levels, and it also increases the levels of anxiety related to functional disability. Epigallocatechin gallate (EGCG) decreases IL-6, which could be enhanced by the anti-inflammatory effect of high ketone bodies after administering coconut oil (both of which are an anxiolytic). Therefore, the aim of this study was to assess the impact of coconut oil and EGCG on the levels of IL-6, anxiety and functional disability in patients with MS.METHODS: A pilot study was conducted for four months with 51 MS patients who were randomly divided into an intervention group and a control group. The intervention group received 800 mg of EGCG and 60 mL of coconut oil, and the control group was prescribed a placebo. Both groups followed the same isocaloric Mediterranean diet. State and trait anxiety were determined before and after the study by means of the State-Trait Anxiety Inventory (STAI). In addition, IL-6 in serum was measured using the ELISA technique and functional capacity was determined with the Expanded Disability Status Scale (EDSS) and the body mass index (BMI).RESULTS: State anxiety and functional capacity decreased in the intervention group and IL-6 decreased in both groups.CONCLUSIONS: EGCG and coconut oil improve state anxiety and functional capacity. In addition, a decrease in IL-6 is observed in patients with MS, possibly due to the antioxidant capacity of the Mediterranean diet and its impact on improving BMI.

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