Melatonin as a Potential Multitherapeutic Agent

Abstract

Melatonin (N-acetyl-5-methoxytryptamine, MEL) is a hormone produced by the pineal gland that was discovered many years ago. The physiological roles of this hormone in the body are varied. The beneficial effects of MEL administration may be related to its influence on mitochondrial physiology. Mitochondrial dysfunction is considered an important factor in various physiological and pathological processes, such as the development of neurodegenerative and cardiovascular diseases, diabetes, various forms of liver disease, skeletal muscle disorders, and aging. Mitochondrial dysfunction induces an increase in the permeability of the inner membrane, which leads to the formation of a permeability transition pore (mPTP) in the mitochondria. The long-term administration of MEL has been shown to improve the functional state of mitochondria and inhibit the opening of the mPTP during aging. It is known that MEL is able to suppress the initiation, progression, angiogenesis, and metastasis of cancer as well as the sensitization of malignant cells to conventional chemotherapy and radiation therapy. This review summarizes the studies carried out by our group on the combined effect of MEL with chemotherapeutic agents (retinoic acid, cytarabine, and navitoclax) on the HL-60 cells used as a model of acute promyelocytic leukemia. Data on the effects of MEL on oxidative stress, aging, and heart failure are also reported.

Melatonin supplementation improves N‐terminal pro‐B‐type natriuretic peptide levels and quality of life in patients with heart failure with reduced ejection fraction: Results from MeHR trial, a randomized clinical trial

“…In experimental studies, melatonin administration inhibited the opening of mitochondrial permeability transition pores in myocytes of the aging ischemic hearts and reversed the functional and biochemical changes in ischemic HF models. 4 , 5 In addition, melatonin prevented myocyte apoptosis and autophagy dysfunction by Atg5‐ and Akt/mTOR‐dependent pathways in pressure overload‐induced cardiac hypertrophy. 22 Also, it protected against diabetic cardiomyopathy via the key melatonin receptor, retinoid‐related orphan receptor α, through various downstream signaling pathways.…”

“…Recently, it has been shown that melatonin has beneficial effects on the cardiovascular system by its cytoprotective and antioxidant properties and by ameliorating mitochondrial dysfunction and regulating the endocrine system, such as SNS and RAAS. 3 , 4 , 5 , 6 Regarding the field of HF, numerous studies demonstrated that melatonin supplementation prevents the development or progression of the disease in animal models of both ischemic and nonischemic HF. 5 Also, observational studies in humans have shown lower melatonin levels in patients with severe HF or those with hypertensive cardiomyopathy who developed HF.…”

Serum metabolomics analysis of deficiency pattern and excess pattern in patients with rheumatoid arthritis

“…Among the specific metabolites of RA DP, 5-methoxytryptamine as the intermediate of melatonin showed a decreasing trend. Melatonin secreted by the pineal gland widely exists in the body, which has the function of scavenging reactive oxygen species and active nitrogen and plays a certain role in hormone secretion, biological rhythm, anti-free radical damage and anti-aging [ 35 , 36 ]. Previous study has found that the level of melatonin with Heart-spleen Deficiency Pattern, one type of CM DPs, is lower than that of normal people, reflecting that melatonin has a certain correlation with DP [ 37 ].…”

Melatonin and Pathological Cell Interactions: Mitochondrial Glucose Processing in Cancer Cells

“…The recent discovery of melatonin in mitochondria [52,112] of healthy cells and its synthesis in these organelles contributes to limiting ROS destruction as melatonin directly scavenges ROS [71,109,[166][167][168] and also stimulates antioxidant enzyme expression. Many studies have confirmed the ability of melatonin to reduce damage to key mitochondrial constituents including proteins of the ETC and the mitochondrial genome [65,168,169], which normally appears under conditions of high oxidative stress. Melatonin's ability to stimulate mitochondrial superoxide dismutase 2 (SOD2) follows its deacetylation signaled by upregulation of the major mitochondrial deacetylase, SIRT3 [168,170,171].…”