Multiple strategies of melatonin protecting against cardiovascular injury related to inflammation: A comprehensive overview

The onset and progression of baneful chronic diseases are often accompanied by a torrent of uncontrolled inflammatory reactions. Although inflammation is a natural response to detect, eliminate, and counterpoise the harmful insults to physiological integrity, a persistent inflammation causes tissue damage or more serious disorders, for example, the atherosclerosis and myocardial infarction. Inflammation often occurs in the cardiovascular system, but are also caused by other disorders including metabolic syndrome, autoimmune diseases, AIDS, and cancer that can affect the cardiac health. To effectively treat heart diseases a potent remedy is necessary which not only suppresses the inflammation but also prevents inflammation-associated cardio-pathogenesis. The ubiquitous antioxidant molecule melatonin has both anti-inflammatory and cardioprotective activities. Melatonin executes its anti-inflammatory activity by its antioxidant function or by targeting multiple intracellular signalling cascades such as modulating cytokine profile, blocking inflammasome activation and apoptosis. Lipid dysregulation and endothelial dysfunction that play a crucial role in the pathogenesis of atherosclerosis, insulin resistance, and diabetes are prevented by melatonin. Attenuation of mitochondrial and ER stress by melatonin is also pertinent to its cardioprotective action. Additionally, melatonin by its immuno-stimulatory activity can suppress inflammaging and immuno-senescence in HIV patients and thereby averts chronic inflammation-induced cardiovascular abnormality in these subjects. Modulation of cytokine profile and decrease in MMP-9 secretion by melatonin is beneficial in autoimmune conditions. In addition to its anti-tumour potency, melatonin can reduce chemotherapy-induced cardio-toxicity in cancer patients. This review, therefore, provides a concise summary of the currently available information appertaining to the roles of melatonin in mitigation of chronic inflammation and its effect on cardiovascular integrity.