Mechanisms of Melatonin in Obesity: A Review

International Journal of Molecular Sciences, Journal Year: 2021, Volume and Issue: 23(1), P. 218 - 218

Published: Dec. 25, 2021

Obesity and its complications have become a prominent global public health problem that severely threatens human health. Melatonin, originally known as an effective antioxidant, is endogenous hormone found throughout the body serves various physiological functions. In recent decades, increasing attention has been paid to unique function in regulating energy metabolism, especially glucose lipid metabolism. Accumulating evidence established relationship between melatonin obesity; nevertheless, not all preclinical clinical indicates anti-obesity effect of melatonin, which makes it remain conclude fight against obesity. this review, we summarized current knowledge obesity-related symptoms, with emphasis on underlying mechanisms. The role profile, adipose tissue, oxidative stress, inflammation, well interactions circadian rhythm, gut microbiota, sleep disorder, α7nAChR, opioidergic system, exosomes, make promising agent open new avenues intervention

Language: Английский

---

Role and Therapeutic Potential of Melatonin in Various Type of Cancers

OncoTargets and Therapy, Journal Year: 2021, Volume and Issue: Volume 14, P. 2019 - 2052

Published: March 1, 2021

Abstract: Cancer is a large group of diseases and the second leading cause death worldwide. Lung, prostate, colorectal, stomach, liver cancers are most common types cancer in men, whereas breast, lung, cervical, thyroid among women. Presently, various treatment strategies, including surgical resection combined with chemotherapy, radiotherapy, nanotherapy, immunotherapy, have been used as conventional treatments for patients cancer. However, clinical outcomes advanced-stage disease remain relatively unfavorable owing to emergence chemoresistance, toxicity, other undesired detrimental side effects. Therefore, new therapies overcome these limitations indispensable. Recently, there has considerable evidence from experimental studies suggesting that melatonin can be prevent treat Studies confirmed mitigates pathogenesis by directly affecting carcinogenesis indirectly disrupting circadian cycle. Melatonin (MLT) nontoxic exhibits range beneficial effects against via apoptotic, antiangiogenic, antiproliferative, metastasis-inhibitory pathways. The combination drugs improves drug sensitivity cancers, solid liquid tumors. In this manuscript, we will comprehensively review some cellular, animal, human literature provide oncostatic anticancer properties. Further, comprehensive compiles available data analyzing history, epidemiology, risk factors, therapeutic effect, significance, alone or chemotherapeutic agents well underlying molecular mechanisms its effect skin, liver, ovarian cancers. Nonetheless, interest readership clarity ease reading, discussed overall mechanism activity different We ended report general conclusions future perspectives. Keywords: receptors, antioxidant, anticancer, apoptosis, angiogenesis, metastasis, therapy,

Language: Английский

---

Revisiting the role of melatonin in human melanocyte physiology: A skin context perspective

Journal of Pineal Research, Journal Year: 2022, Volume and Issue: 72(3)

Published: Feb. 8, 2022

The evolutionarily ancient methoxyindoleamine, melatonin, has long perplexed investigators by its versatility of functions and mechanisms action, which include the regulation vertebrate pigmentation. Although first discovered through potent skin-lightening effects in amphibians, melatonin's role human skin hair follicle pigmentation impact on melanocyte physiology remain unclear. Synthesizing our limited current understanding this role, we specifically examine melanogenesis, oxidative biology, mitochondrial function, senescence, pigmentation-related clock gene activity, with emphasis skin, yet without ignoring instructive pointers from nonhuman species. Given strict dependence epithelial microenvironment, underscore that responses to melatonin are best interrogated a physiological tissue context. Current evidence suggests some metabolites inhibit both, melanogenesis (via reducing tyrosinase activity) proliferation stimulating membrane receptors (MT1, MT2). We discuss whether putative melanogenesis-inhibitory may occur via activation Nrf2-mediated PI3K/AKT signaling, estrogen receptor-mediated and/or melanocortin-1 receptor- cAMP-dependent melatonin-regulated changes peripheral genes regulate namely Bmal1 Per1. Melatonin also accumulate melanocytes where they exert net cyto- senescence-protective as well antioxidative operating free radical scavengers, synthesis activity ROS scavenging enzymes other antioxidants, promoting DNA repair, enhancing function. argue it is clinically biologically important definitively clarify cell culture-based observations translate into melatonin-induced pigmentary context, is, epidermis follicles ex vivo, confirmed clinical trial results. After defining major open questions field, close suggesting how begin answering them relevant, currently available preclinical situ research models.

Language: Английский

---

Physiological Rhythms and Biological Variation of Biomolecules: The Road to Personalized Laboratory Medicine

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(7), P. 6275 - 6275

Published: March 27, 2023

The concentration of biomolecules in living systems shows numerous systematic and random variations. Systematic variations can be classified based on the frequency as ultradian (<24 h), circadian (approximately 24 infradian (>24 which are partly predictable. Random biological known between-subject that among set points an analyte from different individuals within-subject variation, is variation around individuals' points. cannot predicted but estimated using appropriate measurement statistical procedures. Physiological rhythms analytes could considered essential elements predictive, preventive, particularly personalized laboratory medicine. This review aims to summarize research have been done about types physiological rhythms, variations, their effects tests. We searched PubMed Web Science databases for rhythm articles English without time restrictions with terms "Biological Within-subject Between-subject Ultradian Circadian rhythm, Infradian rhythms". It was concluded that, effective management predicting, preventing, personalizing medicine, safe valid interpretation patients' test results, both measurands should simultaneously.

Language: Английский

---

m6A methylation-induced NR1D1 ablation disrupts the HSC circadian clock and promotes hepatic fibrosis

Pharmacological Research, Journal Year: 2023, Volume and Issue: 189, P. 106704 - 106704

Published: Feb. 20, 2023

The roles of nuclear receptor subfamily 1 group d member (NR1D1) and the circadian clock in liver fibrosis remain unclear. Here, we showed that genes, especially NR1D1, were dysregulated mice with carbon tetrachloride (CCl4)-induced fibrosis. In turn, disruption exacerbated experimental NR1D1-deficient more sensitive to CCl4-induced fibrosis, supporting a critical role NR1D1 development. Validation at tissue cellular levels was primarily degraded by N6-methyladenosine (m6A) methylation model, this result also validated rhythm-disordered mouse models. addition, degradation further inhibited phosphorylation dynein-related protein 1-serine site 616 (DRP1S616), resulting weakened mitochondrial fission function increased DNA (mtDNA) release hepatic stellate cell (HSC), which turn activated cGMP-AMP synthase (cGAS) pathway. Activation cGAS pathway induced local inflammatory microenvironment stimulated progression. Interestingly, overexpression observed DRP1S616 restored, HSCs, improved Taken together, our results suggest targeting may be an effective approach prevention management.

Language: Английский

---

Bile acid metabolism and circadian rhythms

AJP Gastrointestinal and Liver Physiology, Journal Year: 2020, Volume and Issue: 319(5), P. G549 - G563

Published: Sept. 9, 2020

Circadian rhythms are biological systems that synchronize cellular circadian oscillators and regulate nutrient absorption utilization. Bile acids important modulators facilitate energy metabolism. acid metabolism related to metabolic diseases, their intersections have not been summarized clearly up now. This review summarizes the molecular association between bile points out future perspectives potential therapeutic targets in diseases.

Language: Английский

---

The interplay between mast cells, pineal gland, and circadian rhythm: Links between histamine, melatonin, and inflammatory mediators

Journal of Pineal Research, Journal Year: 2020, Volume and Issue: 70(2)

Published: Oct. 6, 2020

Abstract Our daily rhythmicity is controlled by a circadian clock with specific set of genes located in the suprachiasmatic nucleus hypothalamus. Mast cells (MCs) are major effector that play protective role against pathogens and inflammation. MC distribution activation associated rhythm via two pathways, IgE/FcεRI‐ IL‐33/ST2‐mediated signaling. Furthermore, there robust oscillation between MC‐specific genes. Melatonin hormone derived from amino acid tryptophan produced primarily pineal gland near center brain, histamine biologically active amine synthesized decarboxylation histidine L‐histidine decarboxylase enzyme. previously reported to modulate rhythms pathways incorporating various modulators which nuclear factor–binding κ light‐chain gene B cells, NF‐κB, common key factor. NF‐κB interacts core disrupts production pro‐inflammatory cytokine mediators such as IL‐6, IL‐13, TNF‐α. Currently, has been no study evaluating interdependence melatonin respect oscillations MCs. Accumulating evidence suggests restoring MCs targeting may be promising therapeutic strategy for MC‐mediated inflammatory diseases. This review summarizes recent findings circadian‐mediated functional roles paradigms, well potentials signaling MC‐dependent

Language: Английский

---

Melatonin supplementation in the management of obesity and obesity-associated disorders: A review of physiological mechanisms and clinical applications

Pharmacological Research, Journal Year: 2020, Volume and Issue: 163, P. 105254 - 105254

Published: Oct. 17, 2020

Language: Английский

---

Synergistic potential of dual andrographolide and melatonin targeting of metastatic colon cancer cells: Using the Chou-Talalay combination index method

European Journal of Pharmacology, Journal Year: 2021, Volume and Issue: 897, P. 173919 - 173919

Published: Feb. 9, 2021

Language: Английский

---

Melatonin Prevents against Ethanol-Induced Liver Injury by Mitigating Ferroptosis via Targeting Brain and Muscle ARNT-like 1 in Mice Liver and HepG2 Cells

Journal of Agricultural and Food Chemistry, Journal Year: 2022, Volume and Issue: 70(40), P. 12953 - 12967

Published: Sept. 27, 2022

The circadian clock acts a pivotal part in human daily physiology and metabolism. Excess alcohol consumption disturbs the rhythm of several metabolism-related genes liver. Melatonin is member foremost hormones secreted by pineal gland with numerous pharmacological properties quite number diseases. However, its potential roles possible mechanisms ethanol-induced ferroptosis are still not clear completely. Ethanol feeding studies were performed upon chronic-plus-binge ethanol protocol C57BL/6 mice or without intraperitoneal injection administration melatonin. HepG2 cells primary hepatocytes subjected to investigation for results showed that melatonin dramatically ameliorated liver injury decreased makers induced ethanol. Meanwhile, effectively reversed misalignment caused Additionally, accelerated Nrf2 nuclear translocation further activated downstream anti-ferroptosis proteins including FTH, FPN, HO-1, SLC7A11 ethanol-changed tissues cells. impact on protection was offset brain muscle ARNT-like 1 (BMAL1) knockdown notably blocked Nrf2-ARE pathway. Altogether, this study revealed could alleviate impeding via reprogramming protein BMAL1 subsequently activating emergence novel protective effects mechanism may provide new dimension prevention intervention against associated

Language: Английский

---