Beneficial effects of melatonin on liver fibrosis: A systematic review of current biological evidence

Abstract

[EN] Hepatic fibrosis is a reversible response to either acute or chronic cellular injury froma wide variety of etiologies, characterized by excessive deposition of extracellularmatrix resulting in liver dysfunction and cirrhosis. Melatonin (N‐acetyl‐5‐methoxytryptamine), the main product secreted by the pineal gland, is a multitaskingindolamine with important physiological functions such as anti‐inflammatory andantioxidant actions, modulation of circadian rhythms, and immune system enhance-ment. Among the numerous biological activities of melatonin, its antifibrotic effectshave received increasingly more attention. In this study, we performed a systematicreview of publications of the last 10 years evaluating the mechanisms of action ofmelatonin against liver fibrosis. The study protocol was registered at PROSPERO(CRD42022304744). Literature research was performed employing PubMed,Scopus, and Web of Science (WOS) databases, and after screening, 29 articleswere included. Results from the selected studies provided denoted the usefulactions of melatonin on the development, progression, and evolution of liver fibrosis.Melatonin antifibrotic effects in the liver involved the reduction of profibrogenicmarkers and modulation of several cellular processes and molecular pathways,mainly acting as an antioxidant and anti‐inflammatory agent. In addition, theindolamine influenced different molecular processes, such as hepatocyte apoptosis,modulation of autophagy and mitophagy, restoration of circadian rhythms, andmodulation of microRNAs, among others. Although some limitations have beenfound regarding variability in the study design, the findings here summarized displaythe potential role of melatonin in ameliorating the development of liver fibrosis andits possible progression to liver cirrhosis and hepatocarcinoma