Journal of Pineal Research最新文献

{"title":"Circadian Rhythm Timing and Associations With Sleep Symptoms in People With Insomnia","authors":"Hannah Scott,&nbsp;Nicole Lovato,&nbsp;Maria Comas,&nbsp;Delwyn Bartlett,&nbsp;Ronald R. Grunstein,&nbsp;Leon Lack,&nbsp;Christopher J. Gordon","doi":"10.1111/jpi.70069","DOIUrl":"https://doi.org/10.1111/jpi.70069","url":null,"abstract":"<p>Circadian rhythmicity plays a crucial role in regulating sleep timing and continuity, but it may be altered in people with insomnia. This study tested whether dim-light melatonin onset (DLMO) timing is associated with sleep difficulties in insomnia. In total, 128 people diagnosed with insomnia disorder were recruited. Participants completed daily sleep diaries and wore an actigraph for up to 14 days before the laboratory visit to estimate mean sleep continuity (e.g., sleep latency, sleep duration) and sleep timing (sleep onset time and wake time from diaries, bedtime from diaries and actigraphy). After a sleep study, participants underwent salivary melatonin collection to estimate DLMO on the following night. Regressions and analyses of variances on tertile groups tested associations between DLMO (clock times and phase angle differences between DLMO and sleep timing) and sleep continuity and timing. There were associations between DLMO and sleep timing, <i>r</i>_<i>(s)</i> = 0.27–0.37, but not with sleep continuity. The phase angle between sleep onset time and DLMO was associated with sleep latency, sleep duration, and sleep efficiency, <i>r</i>_<i>(s)</i> = −0.32 to 0.41. Participants with a longer phase angle between DLMO and sleep onset time (&gt; 3 h; i.e., greater delays) had longer sleep latencies (<i>Mean diff</i> = 43.21 min, <i>SE</i> = 12.99, <i>p</i> = 0.004) and shorter sleep durations (<i>Mean diff</i> = −65.66 min, <i>SE</i> = 20.75, <i>p</i> = 0.006) than participants with a shorter phase angle (&lt; 2 h). Other phase angles (DLMO and mid-sleep, wake time) were not consistently associated with sleep continuity. Melatonin onset timing is associated with sleep timing in insomnia disorder. Larger phase angle differences between sleep onset and DLMO are linked to poorer sleep continuity. These findings highlight the importance of considering circadian alignment and its impact on sleep in understanding the pathophysiology of insomnia and in developing targeted treatment interventions.</p>","PeriodicalId":198,"journal":{"name":"Journal of Pineal Research","volume":"77 5","pages":""},"PeriodicalIF":6.3,"publicationDate":"2025-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jpi.70069","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144773802","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multivariate Data Analysis Methods and Their Application in Lipidomics: A Gentle Comment on Appropriateness and Reliability Criteria","authors":"Anna Migni,&nbsp;Desirée Bartolini,&nbsp;Giada Marcantonini,&nbsp;Roccaldo Sardella,&nbsp;Mario Rende,&nbsp;Alessia Tognoloni,&nbsp;Maria Rachele Ceccarini,&nbsp;Francesco Galli","doi":"10.1111/jpi.70068","DOIUrl":"https://doi.org/10.1111/jpi.70068","url":null,"abstract":"<p>In response to Yoshiyasu Takefuji's critique regarding the use of Principal Component Analysis (PCA) and Partial Least Squares Discriminant Analysis (PLS-DA) in the study “Melatonin Repairs the Lipidome of Human Hepatocytes Exposed to Cd and Free Fatty Acid-Induced Lipotoxicity,” we provide a methodological clarification. PCA and PLS-DA are well-established, widely validated tools for exploratory analysis of high-dimensional omics data, including lipidomics data. Although these methods are linear, they are appropriate for capturing systematic and directional variations in complex biological systems, particularly in controlled in vitro models like ours. Our analytical approach integrates PCA and PLS-DA with rigorous statistical testing, data transformations, and biological validation, ensuring robustness and biological relevance of the findings. We reaffirm that these methods represent a standard, reliable practice in lipidomics, and the potential of nonlinear techniques does not diminish the appropriateness or utility of linear multivariate models when applied with scientific rigor.</p>","PeriodicalId":198,"journal":{"name":"Journal of Pineal Research","volume":"77 4","pages":""},"PeriodicalIF":8.3,"publicationDate":"2025-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jpi.70068","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144672721","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Proteomic Signatures Underlying Sleep, Circadian Activity Patterns, and Major Chronic Diseases","authors":"Jiahe Wei,&nbsp;Hanzhang Wu,&nbsp;Ying Zheng,&nbsp;Bingtao Weng,&nbsp;Yao Xiao,&nbsp;Christian Benedict,&nbsp;Ningjian Wang,&nbsp;Xiang-Hang Luo,&nbsp;Xiao Tan","doi":"10.1111/jpi.70067","DOIUrl":"https://doi.org/10.1111/jpi.70067","url":null,"abstract":"<p>Rest-activity rhythm and sleep may serve as potential intervention targets for a variety of diseases. However, the underlying biological mechanisms of rest-activity rhythm, sleep, and their proteomic associations with multiple diseases remain largely unexplored. Here, using data from approximately 10 000 participants in the UK Biobank with accelerometer-derived measures and proteomics profiles, we characterized the proteomic signatures of rest-activity and sleep and explored their associations with health outcomes. We found that the proteins associated with rest-activity and sleep were mainly enriched in inflammation, immune response and complement system. Most rest-activity and sleep measures, along with their associated proteomic signatures, were significantly associated with incident diabetes, cardiovascular disease, chronic kidney disease, respiratory diseases, and extended life expectancy. Several proteins, such as ADM and CA14, were observed to mediate multiple associations across distinct rest-activity and sleep measures. The impact of rest-activity and sleep measures on chronic diseases and mortality may be mediated through diverse biological pathways involving multiple proteins. These findings reveal potential mechanisms underlying these complex relationships and provide novel insights for the development of targeted intervention strategies.</p>","PeriodicalId":198,"journal":{"name":"Journal of Pineal Research","volume":"77 4","pages":""},"PeriodicalIF":8.3,"publicationDate":"2025-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jpi.70067","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144666260","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Direct Peritoneal Resuscitation and Melatonin in the Treatment of Abdominal Sepsis-Induced Lung Injury via Macrophage Metabolic Reprogramming","authors":"Zhirong Zhao,&nbsp;Jiamin Ji,&nbsp;Lan Ming,&nbsp;Zhaofeng Luo,&nbsp;Mingyi Li,&nbsp;Yuan Chen,&nbsp;Ran Sun,&nbsp;Weiting Lu,&nbsp;Weiliang Tian,&nbsp;Fan Yang,&nbsp;Qian Huang","doi":"10.1111/jpi.70066","DOIUrl":"https://doi.org/10.1111/jpi.70066","url":null,"abstract":"<div>\u0000 \u0000 <p>Abdominal sepsis and the resultant lung injury lead to high mortality rates, with macrophage metabolic dysfunction and subsequent immune dysregulation being key contributing factors. The clarification of the therapeutic value of direct peritoneal resuscitation (DPR) combined with melatonin in regulating macrophage metabolic reprogramming is crucial for the development of potential treatment strategies. Lipopolysaccharide exposure led to a decrease in mitochondrial membrane potential (MMP) of macrophage, morphological changes in mitochondria, and a substantial accumulation of reactive oxygen species (ROS) within the cells. Melatonin protects the stability of the mitochondrial electron transport chain (ETC) by enhancing the synthesis of Uqcrc1, thereby restoring macrophage function. Silencing Uqcrc1 effectively blocked this protective effect. In the rat sepsis model, DPR combined with melatonin enhanced the survival of alveolar macrophages (AMs) and reduced lung tissue damage. Importantly, in the DPR combined with melatonin treated group, the macrophage metabolic reprogramming was evident through enhanced oxidative phosphorylation and increased adenosine triphosphate (ATP) synthesis, both of which contributed to improved immune function and reduced inflammation. It is found that melatonin promotes the synthesis of Uqcrc1, stabilizing the ETC in macrophages. The combination of DPR and melatonin alleviated sepsis-induced lung injury in rats by modulating macrophage metabolic reprogramming.</p>\u0000 </div>","PeriodicalId":198,"journal":{"name":"Journal of Pineal Research","volume":"77 4","pages":""},"PeriodicalIF":8.3,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144624382","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Functional Characterization of GNA1 as a Serotonin N-Acetyltransferase Reveals a Key Role in the Serotonin to Melatonin Pathway in Saccharomyces cerevisiae","authors":"Qingjian Zhang,&nbsp;Dongfeng Cheng,&nbsp;Xianghua Tang,&nbsp;Yibo Li,&nbsp;Nanyu Han,&nbsp;Wei Xu,&nbsp;Junmei Ding","doi":"10.1111/jpi.70065","DOIUrl":"https://doi.org/10.1111/jpi.70065","url":null,"abstract":"<div>\u0000 \u0000 <p>Melatonin (<i>N</i>-acetyl-5-methoxytryptamine) is an evolutionarily conserved molecule with diverse physiological functions across prokaryotes, plants, and animals, including circadian rhythms regulation in animals and developmental modulation in plants. Although the biosynthetic pathways of melatonin have been well elucidated in mammals and plants, the enzymatic mechanisms underlying microbial melatonin synthesis remain largely unexplored. <i>Saccharomyces cerevisiae</i>, a genetically tractable eukaryotic model, provides a valuable system for elucidating fungal melatonin biosynthesis. In this study, we identified the <i>GNA1</i> gene as a potential serotonin <i>N</i>-acetyltransferase candidate in <i>S. cerevisiae</i> through genome-wide comparative analysis. The GNA1 protein was heterologously expressed in <i>Escherichia coli</i> BL21(DE3), purified, and subjected to detailed enzymatic characterization. In vitro assays revealed that GNA1 exhibits acetyltransferase activity toward both serotonin and 5-methoxytryptamine (5-MT), with maximal catalytic efficiency observed at 30°C and pH 8.5. Substrate specificity and kinetic analyses demonstrated a pronounced preference for 5-MT, supporting a biosynthetic route in which serotonin undergoes <i>O</i>-methylation before acetylation by GNA1 to yield melatonin. This study provides the first biochemical evidence linking GNA1 to melatonin biosynthetic pathway in yeast and offers new insights into microbial melatonin biosynthesis, highlighting its potential evolutionary and metabolic significance.</p></div>","PeriodicalId":198,"journal":{"name":"Journal of Pineal Research","volume":"77 4","pages":""},"PeriodicalIF":8.3,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144367283","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Melatonin Prevents Tumor Growth: The Role of Genes Controlling the Circadian Clock, the Cell Cycle, and Angiogenesis","authors":"Skarleth Cardenas-Romero,&nbsp;Nadia Saderi,&nbsp;Oscar Daniel Ramirez-Plascencia,&nbsp;Adrián Baez-Ruiz,&nbsp;Omar Flores-Sandoval,&nbsp;Carolina Escobar Briones,&nbsp;Roberto C. Salgado-Delgado","doi":"10.1111/jpi.70064","DOIUrl":"https://doi.org/10.1111/jpi.70064","url":null,"abstract":"<p>Recent evidence highlights the protective role of melatonin in a variety of pathological conditions, including multiple types of cancer. Epidemiological studies increasingly suggest that exposure to light at night suppresses melatonin synthesis in night-shift and rotating-shift workers, potentially elevating their risk of cancer development. Experimental data further indicate that melatonin can inhibit the proliferation of tumor cells, including glioblastoma-like stem cells. In the present study, we investigated the effect of melatonin on the expression of genes involved in regulating the circadian rhythm, cell cycle progression, and angiogenesis in rats exposed to constant light, a model of circadian disruption. Our findings demonstrate that melatonin administration significantly inhibited tumor growth and reduced the vascularization associated with circadian rhythm disturbance. Molecular analysis revealed that melatonin altered the circadian expression of several genes affecting tumor biology, including <i>p53, TNF-α</i>, <i>Per2</i>, <i>VEGF-A</i>, <i>PDGF-C</i>, and <i>Ang</i>, which are involved in circadian rhythms, cell cycle, and angiogenesis regulation. These results strengthen the existing hypothesis that circadian disruption contributes to tumor progression and suggest that melatonin exerts anticancer effects by modulating circadian gene expression and angiogenesis. Our findings provide further insight into the mechanism by which melatonin may exert oncostatic effects and highlight its potential as a therapeutic agent in cancers associated with circadian rhythm disruption.</p>","PeriodicalId":198,"journal":{"name":"Journal of Pineal Research","volume":"77 4","pages":""},"PeriodicalIF":8.3,"publicationDate":"2025-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jpi.70064","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144292517","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Melatonin Enhances Aquaporin 4 and Alpha-Syntrophin Interaction by Inhibiting Cyclin-Dependent Kinase 5 Activity to Preserve Glymphatic Function in Neonatal Hypoxic-Ischemic Encephalopathy","authors":"Yuan Li,&nbsp;Qingqing Ye,&nbsp;Weitian Lu,&nbsp;Tingsong Li,&nbsp;Shilong Tang,&nbsp;Ting Wei,&nbsp;Pengyu Xiao,&nbsp;Xingfeng Chen,&nbsp;Xiaojuan Wang,&nbsp;Xiaoran Jiang,&nbsp;Mosaab Mohamed Elmahdi,&nbsp;Juan Huang","doi":"10.1111/jpi.70063","DOIUrl":"https://doi.org/10.1111/jpi.70063","url":null,"abstract":"<div>\u0000 \u0000 <p>The glymphatic system is a critical waste clearance system in the brain, playing an essential role in maintaining homeostasis within the central nervous system. Aquaporin 4 (AQP4), an indispensable component of the glymphatic system, is vital for ensuring the proper function of this system. Melatonin has been proven to be protective in treating hypoxic-ischemic encephalopathy (HIE). The aim of this study was to examine if alterations occur in the glymphatic system function in the brain of HIE model rats, and to determine whether melatonin can enhance the function of the glymphatic system by regulating AQP4, along with elucidating the mechanisms underlying melatonin's effects on AQP4. 10-day-old rat pups were subjected to hypoxic-ischemic (HI) injury; melatonin and roscovitine (an inhibitor of cyclin-dependent kinase 5) were injected intraperitoneally at 10 min following HI induction. At 24 h post-HI, intracisternal tracer infusion, neurobehavioral tests, immunofluorescence staining, western blot analysis, Evans blue (EB) permeability assay, brain water content test, ELISA detection, and co-immunoprecipitation tests were performed. At 28 days post-HI, neurobehavioral tests, intracisternal EB infusion, Nissl staining, and cerebral blood flow (CBF) evaluations were performed. The results showed that melatonin improved neurological function, restored glymphatic function, maintained blood–brain barrier integrity, alleviated brain edema, increased CBF, and reduced brain atrophy; both melatonin and roscovitine inhibited cyclin-dependent kinase 5 (CDK5) activity, enhanced the interaction between AQP4 and alpha-syntrophin (α-Syn), and maintained AQP4 polarity. In conclusion, the current study suggests that melatonin may enhance the interaction between AQP4 and α-Syn by inhibiting CDK5 activity after HI to maintain glymphatic function.</p>\u0000 </div>","PeriodicalId":198,"journal":{"name":"Journal of Pineal Research","volume":"77 4","pages":""},"PeriodicalIF":8.3,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144273177","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Standardized and Calibrated Light Stimuli via Head-Mounted Displays for Investigating the Nonvisual Effects of Light","authors":"Maydel Fernandez-Alonso,&nbsp;Manuel Spitschan","doi":"10.1111/jpi.70051","DOIUrl":"https://doi.org/10.1111/jpi.70051","url":null,"abstract":"<p>Light influences human physiology profoundly, affecting the circadian clock and suppressing the endogenous hormone melatonin. Experimental studies often employ either homogenous full-field stimulation, or overhead illumination, which are hard to standardize across studies and laboratories. Here, we present a novel technique to examine nonvisual responses to light using virtual-reality (VR) head-mounted displays (HMDs) for delivering standardized and calibrated light stimuli to observers in a reproducible and controlled manner. We find that VR HMDs are well-suited for delivering standardized stimuli defined in luminance and across time, with excellent properties up to 10 Hz. We examine melatonin suppression to continuous luminance-defined light stimuli in a sample of healthy participants (<i>n</i> = 32, mean ± SD age: 27.2 ± 5.6), and find robust melatonin suppression in 24 out of 32 participants (75% of the sample). Our findings demonstrate that VR HMDs are well-suited for studying the mechanisms underlying human nonvisual photoreception in a reproducible and standardized fashion.</p>","PeriodicalId":198,"journal":{"name":"Journal of Pineal Research","volume":"77 4","pages":""},"PeriodicalIF":8.3,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jpi.70051","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144206920","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Newly Characterized Phytomelatonin Transporter Promotes Tolerance Against Multiple Inorganic Pollutants in Nicotiana benthamiana","authors":"Aditya Banerjee,&nbsp;Aryadeep Roychoudhury","doi":"10.1111/jpi.70061","DOIUrl":"https://doi.org/10.1111/jpi.70061","url":null,"abstract":"<div>\u0000 \u0000 <p>Melatonin is a known pleiotropic antioxidant and signaling molecule, found in both plants and animals. Although melatonin was found to translocate via the human glucose transporter 1 (GLUT1), any mechanism of transporter-mediated uptake of melatonin has remained unknown in plants. In the present manuscript, we found an orthologue of GLUT1 in tobacco and established its role as a functional phytomelatonin transporter (MelT) using fluorescence tracking, via melatonin-conjugated quantum dot nanoparticles. Overexpression of <i>NtMelT</i> in the model plant <i>Nicotiana benthamiana</i> showed increased uptake of the conjugated nanofluorophores to a maximum of 5.4-fold in roots and 2.1-fold in leaves, while application of <i>N</i>-ethylmaleimide (inhibitor of glucose transporter) suppressed their translocation. This ensured the specificity of NtMelT for transporting melatonin. Due to increased uptake and distribution, the transgenic lines maintained a maximum of 4.6-fold more endogenous melatonin. The transgenics were tolerant against arsenic, copper, lead, nickel, and fluoride toxicity. Increased activity of the enzymatic antioxidants detoxified excess reactive oxygen species and alleviated the associated physiological injuries. Translocation of melatonin significantly reduced bioaccumulation of the toxic pollutants and ensured normal flowering and seed setting in the transgenic plants. Overall, the present research provides a solution for safe rice cultivation under polluted environment.</p>\u0000 </div>","PeriodicalId":198,"journal":{"name":"Journal of Pineal Research","volume":"77 4","pages":""},"PeriodicalIF":8.3,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144190850","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Melatonin: A Potential Therapy for Osteoporosis With Insights Into Molecular Mechanisms","authors":"Ko-Hsiu Lu,&nbsp;Yi-Hsien Hsieh,&nbsp;Renn-Chia Lin,&nbsp;Meng-Ying Tsai,&nbsp;Shun-Fa Yang","doi":"10.1111/jpi.70062","DOIUrl":"https://doi.org/10.1111/jpi.70062","url":null,"abstract":"<p>Melatonin is a versatile neurohormone with diverse molecular functions, including sleep regulation, inflammation reduction, antioxidant activity, immune modulation, and anticancer properties. In bone metabolism, it promotes osteoblast formation, inhibits osteoclast activity, and synchronizes skeletal tissue rhythms to support bone health. As melatonin is not yet clinically used for osteoporosis and concerns about the current treatments' side effects remain, this review highlights its role in modulating osteoblast and osteoclast interactions, particularly through regulation of the receptor activator of nuclear factor-κB ligand and osteoprotegerin, to achieve bone-forming and antiresorptive effects. These effects have been demonstrated across various concentrations in diverse cell types and In Vivo models. Furthermore, melatonin safeguards the bone microenvironment by mitigating oxidative stress and inflammation, protecting osteoblasts, preventing bone loss, and maintaining the gut microbiota and brain–gut–bone axis. These attributes underscore melatonin's potential as an effective alternative or complementary therapy for promoting bone health and managing osteoporosis. Future research is needed to determine optimal dosing and timing for maximum efficacy.</p>","PeriodicalId":198,"journal":{"name":"Journal of Pineal Research","volume":"77 4","pages":""},"PeriodicalIF":8.3,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jpi.70062","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144190849","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}