Inflammatory Bowel Disease (IBD), is a debilitating progressive chronic inflammatory
disorder of the small intestine and colon characterized by alternative phases of clinical
relapse and remission. IBD includes two types, Crohn's Disease (CD) and Ulcerative
Colitis (UC), CD can affect any part of the gastrointestinal tract, whereas UC involves
only rectum and colon.
UC is a chronic idiopathic inflammatory disease characterized by relapsing and remitting
mucosal inflammation involving the colon and the rectum. The peak age of disease onset is
between ages 30 years and 40 years. Although the exact etiology of UC remains uncertain,
a combination of patient's immune response, genetics, microbiome, and environment plays
an important role in the development of the inflammation. The incidence of UC is
similarly in men and women, but varies with ethnicity. UC has the highest incidence in
the USA, UK and Sweden. In Egypt, the prevalence is low, but newly diagnosed cases are
increasing rapidly.
The most common signs and symptoms of UC include bloody stool, diarrhea, vomiting,
fatigue, abdominal pain, fever, weight loss with enhanced risk of colorectal cancer and
several extra intestinal manifestations (e.g., arthritis, uveitis, and skin disease).
Symptoms are often non-specific, and patients frequently suffer from long-lasting
subclinical disease activity that is difficult to monitor and treat.
A chronic uncontrolled immune response is the net result of excessive immune activity of
effector lymphocytes with increased production of pro-inflammatory cytokines, while
regulatory immune cells and mediators fail to maintain tissue homeostasis. Chronically
active inflammation is directly coupled to the generation and release by immune cells of
reactive oxygen species (ROS), serving as important signaling molecules that contribute
to their immunological functions. The continuous release of ROS in the local
microenvironment of actively inflamed mucosal lesions causes extensive cellular and
molecular damage, leading to intestinal inflammation and increased tissue destruction.
Oxidative stress which is an imbalance between ROS and antioxidant activity as the result
of either ROS overproduction or a decreased antioxidant activity, has been proposed as
one of the major mechanism involved in the pathophysiology of UC. Once the free radicals
are formed, this reactive species begins to interact with the molecular complexes causing
cellular oxidative damage. Under physiological conditions, their generation is controlled
by the antioxidant system, which consists of enzymes such as superoxide dismutase (SOD),
catalase, and glutathione peroxidase (GPX).
Increased ROS have destructive effects which can affect lipids, proteins, and nucleic
acids that causes lipid peroxidation, enzymatic dysfunction, and DNA strand break
products. These destructive effects can be removed by antioxidant balance, which acts
like free radical scavengers or cellular oxidation inhibitors. The main cellular
antioxidant enzymes involved in the inhibition are catalase, SOD, and GPX. Activated
neutrophils and macrophages are responsible for ROS generation, and their levels can be
correlated with the severity of inflammation. It has been shown that IL 1 and TNFα
cytokines can be inhibited by antioxidants administered to patients with
UlcerativeColitis.
The American College of Gastroenterology (ACG) recommends performing a complete blood
count (CBC), and measuring inflammatory markers such as c-reactive protein (CRP),
erythrocyte sedimentation rate (ESR). It also recommends measuring Liver transaminases
(aspartate and alanine aminotransferase). Measurement of fecal calprotectin is useful for
screening intestinal inflammation associated with disease activity.
Silymarin (milk thistle), an extract obtained from Silybum marianum seeds, is one of
these natural sources containing a complex of flavonolignans with a potent intracellular
antioxidant property. The first usage of Milk thistle was for its hepatoprotective and
antioxidant activities, but in the recent years its benefit has been reported in control
of immune based murine colitis by healing of bowel histology and reduction of bowel
inflammatory cytokines especially TNF-α, interleukin-1β (IL-1β), and nuclear factor κB
(NF-κB). Silymarin has numerous health benefits and exerts its effects via various
molecular mechanisms. Silymarin has anti-viral, immunomodulation, anti-inflammatory
effects as well as antioxidant properties by scavenging free radicals and increasing the
glutathione concentrations, anti-arthritis, antidiabetic, protective and wound healing
effects.