Melatonin: Translation of Ongoing Studies Into Possible Therapeutic Applications Outside Sleep Disorders

Leelaviwat, Natnicha; Mekraksakit, Poemlarp; Cross, Kristina M.; Landis, Dylan; McLain, Madison; Sehgal, Laveena; Payne, Drew

doi:10.1016/j.clinthera.2022.03.008

Cited by 6 publications

(3 citation statements)

References 203 publications

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“…The melatonin is further metabolized into 6-hydroxymelatonin (6OH-MEL) by human cytochrome P450 family [ 4 ]. Evidence shows that various biological properties of melatonin, such as the circadian clock [ 5 , 6 , 7 ], sleep regulation [ 8 , 9 ], anti-inflammatory properties [ 10 , 11 , 12 ], immune modulation [ 13 , 14 , 15 ], and anti-cancer activities [ 16 , 17 , 18 ], have been well revealed. Nevertheless, the clinical and immunological function of the cytochrome P450 family in cancer remains unclear.…”

Section: Introductionmentioning

confidence: 99%

CYP1B1: A Novel Molecular Biomarker Predicts Molecular Subtype, Tumor Microenvironment, and Immune Response in 33 Cancers

Yuan

Liu

Dai

et al. 2022

Cancers

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Background: Cytochrome P450 Family 1 Subfamily B Member 1 (CYP1B1) is a critical metabolic enzyme of melatonin. Although melatonin has been identified to exhibit tumor suppressing activity, the role and mechanism of the clinical and immunological characteristics of CYP1B1 in cancer remain unclear. Methods: In this study, RNA expression and clinical data were obtained from The Cancer Genome Atlas (TCGA) across 33 solid tumors. The expression, survival, immune subtype, molecular subtype, tumor mutation burden (TMB), microsatellite instability (MSI), biological pathways, and function in vitro and vivo were evaluated. The predictive value of CYP1B1 in immune cohorts was further explored. Results: We found the dysregulated expression of CYP1B1 was associated with the clinical stage and tumor grade. Immunological correlation analysis showed CYP1B1 was positively correlated with the infiltration of lymphocyte, immunomodulator, chemokine, receptor, and cancer-associated fibroblasts (CAFs) in most cancer. Meanwhile, CYP1B1 was involved in immune subtype and molecular subtype, and was connected with TMB, MSI, neoantigen, the activation of multiple melatonergic and immune-related pathways, and therapeutic resistance. Conclusions: Together, this study comprehensively revealed the role and mechanism of CYP1B1 and explored the significant association between CYP1B1 expression and immune activity. These findings provide a promising predictor and molecular target for clinical immune treatment.

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Section: Introductionmentioning

confidence: 99%

CYP1B1: A Novel Molecular Biomarker Predicts Molecular Subtype, Tumor Microenvironment, and Immune Response in 33 Cancers

Yuan

Liu

Dai

et al. 2022

Cancers

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“…Melatonin is a natural hormone synthesized by the pineal gland and controlled by the circadian rhythm [ 10 ]. Some reports found that Plasmodium becomes more synchronized by melatonin [ 11 , 12 ].…”

Section: Introductionmentioning

confidence: 99%

Antimalarial effect of synthetic endoperoxide on synchronized Plasmodium chabaudi infected mice

Aly

Matsumori²,

Dinh³

et al. 2023

Parasit Host Dis

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The discovery of new antimalarial drugs can be developed using asynchronized Plasmodium berghei malaria parasites in vivo in mice. Studies on a particular stage are also required to assess the effectiveness and mode of action of drugs. In this report, we used endoperoxide 6-(1,2,6,7-tetraoxaspiro [7.11] nonadec-4-yl) hexan-1-ol (N-251) as a model antimalarial compound on P. chabaudi parasites. We examined the antimalarial effect of N-251 against ring-stage- and trophozoite-stage-rich P. chabaudi parasites and asynchronized P. berghei parasites using the 4-day suppressive test. The ED50 values were 27, 22, and 22 mg/kg, respectively, and the antimalarial activity of N-251 was verified in both rodent malaria parasites. To assess the stage-specific effect of N-251 in vivo, we evaluated the change of parasitemia and distribution of parasite stages using ring-stage- and trophozoite-stage-rich P. chabaudi parasites with one-day drug administration for one life cycle. We discovered that the parasitemias decreased after 13 and 9 hours post-treatment in the ring-stage- and trophozoite-stage-rich groups, respectively. Additionally, in the ring-stage-rich N-251 treated group, the ring-stage parasites hindered trophozoite parasite development. For the trophozoite-stage-rich N-251 treated group, the distribution of the trophozoite stage was maintained without a change in parasitemia until 9 hours. Because of these findings, it can be concluded that N-251 suppressed the trophozoite stage but not the ring stage. We report for the first time that N-251 specifically suppresses the trophozoite stage using P. chabaudi in mice. The results show that P. chabaudi is a reliable model for the characterization of stage-specific antimalarial effects.

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“…Melatonin effectively shortened the time to fall asleep, reduced the time of light sleep, increased the time of deep sleep, improved sleep quality, and helped people stay awake after waking up. Additionally, there is good evidence that melatonin can be used to treat ischemia-reperfusion injury, primary headache, and fibromyalgia and can control blood sugar and blood pressure (Leelaviwat et al, 2022). Melatonin is increasingly valued by patients and clinicians due to its antioxidant and antiaging properties.…”

Section: Introductionmentioning

confidence: 99%

The role of melatonin in the development of postmenopausal osteoporosis

Yang

Qiu²,

Cao³

et al. 2022

Front. Pharmacol.

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Melatonin is an important endogenous hormone that modulates homeostasis in the microenvironment. Recent studies have indicated that serum melatonin levels are closely associated with the occurrence and development of osteoporosis in postmenopausal women. Exogenous melatonin could also improve bone mass and increase skeletal strength. To determine the underlying mechanisms of melatonin in the prevention and treatment of postmenopausal osteoporosis, we performed this review to analyze the role of melatonin in bone metabolism according to its physiological functions. Serum melatonin is related to bone mass, the measurement of which is a potential method for the diagnosis of osteoporosis. Melatonin has a direct effect on bone remodeling by promoting osteogenesis and suppressing osteoclastogenesis. Melatonin also regulates the biological rhythm of bone tissue, which benefits its osteogenic effect. Additionally, melatonin participates in the modulation of the bone microenvironment. Melatonin attenuates the damage induced by oxidative stress and inflammation on osteoblasts and prevents osteolysis from reactive oxygen species and inflammatory factors. As an alternative drug for osteoporosis, melatonin can improve the gut ecology, remodel microbiota composition, regulate substance absorption and maintain metabolic balance, all of which are beneficial to the health of bone structure. In conclusion, our review systematically demonstrates the effects of melatonin on bone metabolism. Based on the evidence in this review, melatonin will play a more important role in the diagnosis, prevention and treatment of postmenopausal osteoporosis.

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Melatonin: Translation of Ongoing Studies Into Possible Therapeutic Applications Outside Sleep Disorders

Cited by 6 publications

References 203 publications

CYP1B1: A Novel Molecular Biomarker Predicts Molecular Subtype, Tumor Microenvironment, and Immune Response in 33 Cancers

CYP1B1: A Novel Molecular Biomarker Predicts Molecular Subtype, Tumor Microenvironment, and Immune Response in 33 Cancers

Antimalarial effect of synthetic endoperoxide on synchronized Plasmodium chabaudi infected mice

The role of melatonin in the development of postmenopausal osteoporosis

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