Functional interplay of melatonin in the bile duct and gastrointestinal tract to mitigate disease development: An overview

Prevalence of bile duct and gastrointestinal (GI) tract associated diseases is increasing globally. Commonly, the bile duct epithelial cell (cholangiocytes) malfunction and its uncontrolled proliferation often cause liver fibrosis and tumorigenesis, particularly the cholangiocarcinoma. Specifically, GI tract is constantly under diverse endogenous and exogenous stressors which interrupt GI physiological functions and promote inflammation, tissue damage, ulceration, gastrointestinal bleeding, gastroesophageal reflux disease (GERD), irritable bowel disease (IBD) and gastritis. On the other hand, melatonin exhibits important functions in both cholangiocyte and GI tract. The abundance of melatonin generated in the GI tract and its widely distributed receptors facilitate its protective effects in GI tissues. In the most of the cases, the disease progression in GI tract, particularly in bile duct, is associated with endogenous melatonergic system suppression. Therefore, to increase the endogenous melatonin production appears a suitable strategy to retard the disease development in these tissues. Melatonin administration or, exposure to prolonged darkness not only reverse the detrimental biochemical alterations, but also inhibit cholangiocyte proliferation as well as ulceration in the GI tract. Thus, use of melatonin as a natural therapeutic agent is beneficial and exhibits advantages over other contemporary drugs in prevention and treatment of bile duct and gastrointestinal tract associated diseases.