Re: Research: Scientists discover anti-inflammatory polyphenols in apple peels

[Kofi]

Given the role of CXCR3 in mediating this effect, apple polyphenols may
be of interest to Celiac patients and type I diabetics. Also note this
may be mimicking the effects of vitamin D3.

It's funny. The only two fruits I can stomach are green apples and
grapefruit. I found out recently grapefruit contains a PPARalpha
agonist. Now I know green apples are directly beneficial for colitis.


Celiac disease is an immune-mediated enteropathy triggered by gliadin, a
component of the grain protein gluten. Gliadin induces an
MyD88-dependent zonulin release that leads to increased intestinal
permeability, a postulated early element in the pathogenesis of celiac
disease. We aimed to establish the molecular basis of gliadin
interaction with intestinal mucosa leading to intestinal barrier
impairment. METHODS: Alpha-gliadin affinity column was loaded with
intestinal mucosal membrane lysates to identify the putative
gliadin-binding moiety. In vitro experiments with chemokine receptor
CXCR3 transfectants were performed to confirm binding of gliadin and/or
26 overlapping 20mer alpha-gliadin synthetic peptides to the receptor.
CXCR3 protein and gene expression were studied in intestinal epithelial
cell lines and human biopsy specimens. Gliadin-CXCR3 interaction was
further analyzed by immunofluorescence microscopy, laser capture
microscopy, real-time reverse-transcription polymerase chain reaction,
and immunoprecipitation/Western blot analysis. Ex vivo experiments were
performed using C57BL/6 wild-type and CXCR3(-/-) mouse small intestines
to measure intestinal permeability and zonulin release. RESULTS:
Affinity column and colocalization experiments showed that gliadin binds
to CXCR3 and that at least 2 alpha-gliadin 20mer synthetic peptides are
involved in this binding. CXCR3 is expressed in mouse and human
intestinal epithelia and lamina propria. Mucosal CXCR3 expression was
elevated in active celiac disease but returned to baseline levels
following implementation of a gluten-free diet. Gliadin induced physical
association between CXCR3 and MyD88 in enterocytes. Gliadin increased
zonulin release and intestinal permeability in wild-type but not
CXCR3(-/-) mouse small intestine. CONCLUSIONS: Gliadin binds to CXCR3
and leads to MyD88-dependent zonulin release and increased intestinal
permeability [PMID 18485912]

insulitic lesions were characterized by presence of beta cells, elevated
levels of the chemokine CXCL10 and infiltration of lymphocytes
expressing the corresponding chemokine receptor CXCR3 in all pancreatic
lesions of type 1 diabetes patients, regardless of enterovirus infection
of beta cells [PMID 20059481]

CXCR3 is downregulated by sympathetic flow (ADRB1) in the skin, which
activates NK cells and PDCs [PMID 17716858]

heparin inhibits the production of CXCR3 ligands by disrupting IFN-gamma
responses and also interfering with binding of ligands to CXCR3, thus
limiting arteriosclerotic inflammation [PMID 16940188]

Vitamin D has been associated with a decreased risk of multiple
sclerosis (MS). In this study, serum 1, 25-dihydroxyvitamin D (1,
25-(OH)2 vitD) and 25-hydroxyvitamin D (25-OH vitD), regulatory T cell
percentages and naive and memory T helper cell subsets were measured in
26 patients with multiple sclerosis, 21 who were not on treatment with
disease modifying therapy. These studies showed an inverse correlation
between 25-OH vitD levels and Treg cell percentages and a direct
correlation between Treg cell percentages and 1, 25-(OH)2 vitD:25-OH
vitD ratios. In addition, 25-OH vitD levels correlated directly and 1,
25-(OH)2 vitD:25-OH vitD ratios correlated inversely with CXCR3+ naive T
helper cell percentages and CXCR3+naive:CXCR3+ memory T helper cell
ratios. All together, these data demonstrate that vitamin D measurements
can reflect measures of immune status among patients with MS [PMID
19539379]


J Leukoc Biol. 2011 Dec;90(6):1043-54. Epub 2011 Jun 21.Related
Citations, LinkOut

Apple polyphenols require T cells to ameliorate dextran sulfate
sodium-induced colitis and dampen proinflammatory cytokine expression.
* Skyberg JA,
* Robison A,
* Golden S,
* Rollins MF,
* Callis G,
* Huarte E,
* Kochetkova I,
* Jutila MA,
* Pascual DW.

1. Montana State University, P.O. Box 173610, Bozeman, MT 59717-3610,
USA.

Human IBD, including UC and Crohn's disease, is characterized by a
chronic, relapsing, and remitting condition that exhibits various
features of immunological inflammation and affects at least one/1000
people in Western countries. Polyphenol extracts from a variety of
plants have been shown to have immunomodulatory and anti-inflammatory
effects. In this study, treatment with APP was investigated to
ameliorate chemically induced colitis. Oral but not peritoneal
administration of APP during colitis induction significantly protected
C57BL/6 mice against disease, as evidenced by the lack of weight loss,
colonic inflammation, and shortening of the colon. APP administration
dampened the mRNA expression of IL-1beta, TNF-alpha, IL-6, IL-17, IL-22,
CXCL9, CXCL10, CXCL11, and IFN-gamma in the colons of mice with colitis.
APP-mediated protection requires T cells, as protection was abated in
Rag-1(-/-) or TCRalpha(-/-) mice but not in IL-10(-/-), IRF-1(-/-),
muMT, or TCRdelta(-/-) mice. Administration of APP during colitis to
TCRalpha(-/-) mice actually enhanced proinflammatory cytokine
expression, further demonstrating a requirement for TCRalphabeta cells
in APP-mediated protection. APP treatment also inhibited CXCR3
expression by TCRalphabeta cells, but not B or NK cells, in the colons
of mice with colitis; however, depletion of CD4(+) or CD8(+) T cells
alone did not abolish APP-mediated protection. Collectively, these
results show that oral administration of APP protects against
experimental colitis and diminishes proinflammatory cytokine expression
via T cells.

PMID: 21693591


In article
<839be234-5839-4b0f...@da3g2000vbb.googlegroups.com>,
zumone2002 <zumon...@yahoo.com> wrote:

> http://www.eurekalert.org/pub releases/2011-11/foas-sda113011.php
>
> Scientists discover anti-inflammatory polyphenols in apple peels
> New research published in the Journal of Leukocyte Biology suggests
> that oral ingestion of apple polyphenols can suppress T cell
> activation and ameliorate experimental colitis in mice
>
> Bethesda, MD稀ere's another reason why "an apple a day keeps the
> doctor away"蟻ccording to new research findings published in the
> Journal of Leukocyte Biology (https://www.jleukbio.org), oral
> ingestion of apple polyphenols (antioxidants found in apple peels) can
> suppress T cell activation to prevent colitis in mice. This study is
> the first to show a role for T cells in polyphenol-mediated protection
> against an autoimmune disease and could lead to new therapies and
> treatments for people with disorders related to bowel inflammation,
> such as ulcerative colitis, Crohn's disease and colitis-associated
> colorectal cancer.
>
> "Many people with colitis use some form of dietary supplement to
> complement conventional therapies, but most of the information on the
> health effects of complementary medicine remains anecdotal. Also,
> little is known about exactly how these therapies work, if they work
> at all," said David W. Pascual, Ph.D., a researcher involved in the
> work from the Department of Immunology and Infectious Diseases at
> Montana State University in Bozeman, Montana. "Our results show that a
> natural product found in apple peels can suppress colonic inflammation
> by antagonizing inflammatory T cells to enhance resistance against
> autoimmune disease."
>
> To make this discovery, scientists used a chemically induced model of
> colitis with Dextran sulfate sodium (DSS), researchers administered an
> oral placebo to one group of mice, and the other group of mice was
> given an oral dose of apple polyphenols every day during the course of
> the disease. Results showed that mice treated orally with apple
> polyphenols were protected from colitis. Importantly, scientists also
> found that the treated mice had fewer activated T cells in their
> colons. In mice lacking T cells, apple polyphenols were unable to
> protect against colitis or suppress proinflammatory cytokine
> expression, indicating apple polyphenols protect against colitis via
> the suppression of T cell activation and/or recruitment.
>
> "It appears that the old adage rings true in more ways than one," said
> John Wherry, Ph.D., Deputy Editor of the Journal of Leukocyte Biology,
> "In addition to the obvious health benefits of the nutrients and fiber
> in fruits and vegetables, this study indicates that even something as
> relatively common as the apple contains other healthy ingredients that
> can have serious therapeutic value."
>
> --
> Luke

[lon]

'Young' home grown (or proven organic) green skinned apples would be the
most beneficial ?

>> Bethesda, MD‹Here's another reason why "an apple a day keeps the
>> doctor away"‹according to new research findings published in the