Beneficial Effect of Silymarin in Ulcerative Colitis

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.