The hormone melatonin, known for regulating circadian rhythms, is explored for its broader functions, including immune-modulation, anti-inflammatory, and antioxidant effects. Recent studies suggest melatonin’s potential therapeutic benefits in treating complications related to diabetes, cancer, Alzheimer’s disease, immune disorders, and heart diseases, focusing on vascular biology. Melatonin is produced not only in the pineal gland but also in various organs. Its synthesis involves several steps, starting from the amino acid tryptophan. It highlights the function of MT1 and MT2 melatonin receptors and their signaling pathways in physiology and disease. The section emphasizes melatonin’s antioxidative properties and its potential applications in reducing oxidative stress and inflammation, particularly in cardiovascular diseases. It reviews the therapeutic perspective of melatonin receptors in treating conditions like atherosclerosis and endothelial dysfunction. Specific comments: 1. The introduction provides a clear overview of melatonin’s functions. Could you elaborate on how melatonin’s role in vascular biology is currently understood in the scientific community? 2. Figure 2 outlines the melatonin synthesis pathway. Is there any recent research that provides further insight into this process, particularly in non-pineal tissues? 3. The paper mentions age-related variations in melatonin levels. How might these variations affect vascular health across different age groups? 4. The authors discussed the functions of melatonin receptors MT1 and MT2. Can you provide more details on how these receptors specifically contribute to cardiovascular protection? 5. The antioxidant properties of melatonin are well-noted. Could the paper include a comparison with other antioxidants to highlight melatonin’s unique benefits? 6. The anti-inflammatory effects of melatonin are mentioned. It would be beneficial to include a discussion on the interplay between melatonin and common inflammatory markers in vascular diseases. 7. The therapeutic potential of melatonin in treating vascular dysfunction is intriguing. Could future research directions be suggested for clinical applications? 8. While melatonin is generally considered safe, could you discuss any known side effects or recommended dosages for vascular health applications? 9. Some of the figures are not labeled properly or are too small to read. I recommend revising these figures to make them more clear and readable.