And effective therapy for inflammatory bowel disease August 25, 2003(Bethesda,
md)Inflammatory bowel disease(Ibd)Refers to crohn's disease and ulcerative
colitis, debilitating illnesses characterized by chronic recurrent ulceration of
the bowel, abdominal pain, digestive problems, diarrhea or constipation.The
national institutes of health estimates that some two million americans suffer
from visitthisuser'swebsite this
disorder, which is of unknown origin, but likely caused by a combination of
genetic, environmental, and immunologic factors. Medical researchers have made
considerable efforts to establish a genetic linkage between crohn's disease and
the nod2 protein associated with programmed cell death and activation of nf b, a
transcription factor involved in the production of cytokines and chemokines
necessary for inflammation. Regulation of nf b function has been documented by
several agents used in the management of ibd, such as corticosteroids,
sulfasalazine, and 5aminosalicylates(5ASA).Furthermore, antisense
oligonucleotides directed against the p65 subunit(A polypeptide contributing to
the activation of nf b)Have been shown to diminish disease activity in an animal
model of colitis.Recent work has shown that dietary constituents such as
curcumin may also potently inhibit nf b and diminish attenuate proinflammatory
molecule expression.Curcumin is a component of the spice turmeric(Curcuma
longa)Used in curries and mustard, whose antiinflammatory properties have been
recognized for years.These effects are related, in part, to inhibition of the
activities of the cyclooxygenase, lipoxygenase, and nf b beats by dre pro
sale in several cell systems.Furthermore, its role in the attenuation of
colonic cancer in animal models has also been established. Management of ibd
involves the use of 5asa and immunosuppressives such as corticosteroids and
6mercaptopurine as well as its precursor azathioprine.Novel agents such as
monoclonal antibodies against tnf have been developed and demonstrate clinical
efficacy.However, these agents are expensive and not without side
effects.Consequently, there is a need for alternative agents that may be equally
or more effective as well as being cheaper.Both curcumin and sulfasalazine
target ikk molecules;The importance of inhibition of i?B kinase complex by
curcumin has never been tested in ibd.Here researchers show that this compound
has beneficial effects in a rat model of ibd, opening the door to possible
future human studies. A new study http://www.teamskyuser.co.uk/ The
new study now provides the first evaluation of curcumin and its effects on nf b
in an experimental model of ibd.Salh, k.Assi, k.Parhar, d.Owen, and a.Gmezmuoz,
at the jack bell research centre at the vancouver general hospital, and
v.Templeman and k.Jacobson of the department of pediatric gastroenterology,
children and women's hospital, all in vancouver, british columbia, canada.Their
findings appear in the july 2003 edition of the american journal of
physiologygastrointestinal and liver physiology.Sevenweekold c3h mice had
inflammation induced with instillation of 100 l of dnb(60 mg/ml)In 50% ethanol
with control animals receiving 100 l of 50% ethanol alone.After this, they were
kept in position for 30 seconds before being returned to their cages.On day 5,
postinduction was conducted for evaluation of the colitis.Test groups of five
mice had curcumin added to their diet at a concentration of 0.25% beginning five
days before the DNB instillation. Several parameters were determined in the
inflamed mucosa.Animals were weighed daily after induction of colitis and the
data shown are representative of all experiments.There was a clear reduction in
the amount of weight loss in the animals pretreated with curcumin. Curcumin
improves intestinal cell function in dnbinduced colitis.After treatment of
animals, colons were harvested and histological evaluation was carried out after
staining with hematoxylin and eosin.There was mucosal ulceration, thickening of
the wall, and significant infiltration with inflammatory cells in the dnbtreated
animals that is reduced in those animals pretreated with curcumin. When animals
were pretreated with curcumin, there was a clear reduction in dna binding, thus
verifying that curcumin does indeed inhibit nf b activation in the colon in
vivo.These findings indicate for the first time that curcumin is able to impact
on an important transcriptional mechanism in the gastrointestinal tract.In
addition to the demonstration that it is able to diminish inflammatory activity
in ibd, the canadian team demonstrated it can reduce nf b dna binding activity
as well as inhibiting the activation of p38 mapk antibodies and that the
antiinflammatory effects of curcumin involve a reduction in myeloperoxidase
activity, a reduction in the number of infiltrating neutrophils, as well as a
reduced expression of the message for il1. Precisely how curcumin achieves its
effects is not clear.It has been shown to possess free radical
scavenging(Antioxidant)Properties in addition to its known effects on the
activation of nf b.Its in vivo effects may well rely on a complementation of
these two and other activities. Although curcumin has been shown to be safe up
to levels as high as 10 percent(100, 000 ppm), the researchers showed
effectiveness at a concentration as low as 0.25 percent.This dose was well
tolerated with no reduction in dietary intake.Further work will help to clarify
the optimal dose for this and other models of ibd. This research proves that
curcumin may prove to be a cheap, welltolerated, and effective therapy for
inflammatory bowel disease.This food ingredient has for generations been
regarded as a potent antiinflammatory within many eastern civilizations.It is
equally intriguing that the same agent is a potent antineoplastic agent.It may
hold promise for the treatment of ibd in humans. Source:July 2003 edition of the
american journal of physiologygastrointestinal and liver physiology. The
american physiological society(Aps)Was founded in 1887 to foster basic and
applied science, much of it relating to human health.The bethesda, mdbased
society has more than 10, 000 members and publishes 3, 800 articles in its 14
peerreviewed journals every year.
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