- Melatonin mitigates oxidative stress and preserves mitochondrial function, protecting liver from alcohol and toxin induced damage.
- Melatonin improves insulin sensitivity, regulates lipid metabolism, and reduces hepatic steatosis and pro-inflammatory cytokine signalling in NAFLD and steatohepatitis.
- Melatonin inhibits hepatic stellate cell activation to reduce fibrosis and induces apoptosis and anti-angiogenesis in HCC; large RCTs needed to confirm clinical use.
Front Pharmacol. 2026 Sep 10;17:1931181. doi: 10.3389/fphar.2026.1931181. eCollection 2026.
ABSTRACT
The hormone melatonin, secreted by the pineal gland, has attracted considerable interest due to its potential to prevent liver disorders by its strong antioxidant characteristics. This review examines the diverse functions of melatonin in maintaining liver health, with a specific emphasis on its mechanisms of action in different liver diseases. Melatonin counteracts the harmful effects of alcohol on the liver by reducing oxidative stress and maintaining the proper functioning of mitochondria. Melatonin improves insulin sensitivity and regulates lipid metabolism in metabolic liver diseases, such as non-alcoholic fatty liver disease (NAFLD), and decreasing hepatic steatosis. The anti-inflammatory properties of this substance are obtained by reducing pro-inflammatory cytokines signaling pathways, which protect against diseases such as hepatitis and steatohepatitis. In addition, melatonin demonstrates anti-fibrotic characteristics by inhibiting the activation of hepatic stellate cells and decreasing the production of fibrogenic cytokines, reducing the severity of liver fibrosis. Within the realm of hepatocellular carcinoma (HCC), melatonin triggers programmed cell death that hinders the growth of cells and represses the formation of new blood vessels, augmenting the effectiveness of traditional treatments. Research has shown that melatonin is safe and effective in treating liver problems. However, further large-scale, multicenter randomized clinical trials are required to establish the optimal therapeutic dose, treatment duration, long-term safety, and clinical efficacy of melatonin in patients with liver diseases. Future research should focus on clarifying the specific molecular targets of melatonin, enhancing its bioavailability, and creating combination therapies. The existing evidence indicates that melatonin is a potentially beneficial supplementary treatment and preventive medication for liver disorders, owing to its antioxidant, anti-inflammatory, anti-fibrotic, and metabolic regulating characteristics. Nonetheless, additional well designed clinical trials are necessary to determine its ideal therapeutic use and promote its integration into clinical practice.
PMID:42787377 | PMC:PMC13601304 | DOI:10.3389/fphar.2026.1931181
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