Melatonin promotes gastric healing by modulating the components of matrix metalloproteinase signaling pathway: a novel scenario for gastric ulcer management

Over the past few decades, since the induction of antibiotics and proton pump inhibitors (PPI) as a therapeutic tool in controlling gastropathy, a substantial decline in the incidence of gastric ulcer and its related manifestations has been achieved globally. However, there are a lot of skeptics on the steady rise in the list of complications following long-term use of these drugs, especially in chronic and elderly patients. Hence, the search for a sustainable cure for these gastropathies has never actually ended; this let us consider that melatonin, an endogenous antioxidant, might have a utility in this respect. Although researchers have linked melatonin with accelerated post ulcerative wound healing, many of these studies have failed to identify the confounding factors and plausible healing mechanisms. In this review, we attempt to identify the underline mechanisms as to the protective effects of melatonin on a variety of gastropathies. Based on the evidence, we select the matrix metalloproteinases (MMPs) to be the main targets of melatonin. MMPs play a key role in maintaining the balance between extracellular matrix degradation and tissue remodeling, therefore, they act as the integral connection between the ulcer manifestation and healing. Thus, gastric ulceration occurs where this balance is disrupted. Melatonin can preserve this balance during the onset of gastric ulcers. In this review, we have also discussed the effects of melatonin on the different isoforms of MMPs and their roles in gastric ulceration, respectively. We hope that this will bestow us with a better understanding of the development of the gastric ulcer, as well as its cure.