Plant-derived melatonin from food: a gift of nature.

In recent years, people have become increasingly interested in bioactive ingredients from plants, especially antioxidant molecules such as melatonin, which are beneficial to human health. The purpose of this article is to provide new information on plant-derived foods with a high content of melatonin. We comprehensively summarize the content of melatonin in plant-derived foods and discuss the factors that influence melatonin levels to provide new ideas on enhancement. Additionally, we describe the biosynthetic pathway of melatonin and identify its major functions. Medicinal herbs are often rich in melatonin while many vegetables and fruits exhibit somewhat lower levels with wide variations among species. The genetic traits of plants, the phenological stage of the cultivar, the photoperiod, the level of stress to which the plants are exposed at the time of harvest, exposure to agrochemicals and determination methods are the main factors affecting the melatonin content. To date, standardization of uniform sampling times and the use of suitable pretreatments as well as determination methods have not been achieved. The results of the studies reviewed highlight the potentially important role of plant melatonin in influencing the progression of human diseases. Based on the health promotional aspects of melatonin, consuming foods containing higher concentrations of tryptophan and melatonin is suggested.

[1]  R. Reiter,et al.  Clinical Trials for Use of Melatonin to Fight against COVID-19 Are Urgently Needed , 2020, Nutrients.

[2]  R. Reiter,et al.  Use of Melatonin in Oxidative Stress Related Neonatal Diseases , 2020, Antioxidants.

[3]  R. Reiter,et al.  An evolutionary view of melatonin synthesis and metabolism related to its biological functions in plants. , 2020, Journal of experimental botany.

[4]  D. Tan,et al.  Potential utility of melatonin in deadly infectious diseases related to the overreaction of innate immune response and destructive inflammation: focus on COVID-19 , 2020 .

[5]  Kai Zhao,et al.  A pneumonia outbreak associated with a new coronavirus of probable bat origin , 2020, Nature.

[6]  R. Reiter,et al.  Potential use of melatonin in skin cancer treatment: A review of current biological evidence , 2019, Journal of cellular physiology.

[7]  D. Cardinali Melatonin: Clinical Perspectives in Neurodegeneration , 2019, Front. Endocrinol..

[8]  R. Reiter,et al.  The role of melatonin in targeting cell signaling pathways in neurodegeneration , 2019, Annals of the New York Academy of Sciences.

[9]  R. Reiter,et al.  Melatonin Synthesis and Function: Evolutionary History in Animals and Plants , 2019, Front. Endocrinol..

[10]  Zhenlong Xin,et al.  Melatonin: Another avenue for treating osteoporosis? , 2019, Journal of pineal research.

[11]  S. Munné-Bosch,et al.  Biosynthesis, Metabolism and Function of Auxin, Salicylic Acid and Melatonin in Climacteric and Non-climacteric Fruits , 2019, Front. Plant Sci..

[12]  R. Reiter,et al.  Exogenous melatonin as a treatment for secondary sleep disorders: A systematic review and meta-analysis , 2019, Frontiers in Neuroendocrinology.

[13]  R. Reiter,et al.  Melatonin actions in the heart; more than a hormone , 2018, Melatonin Research.

[14]  H. Yip,et al.  Melatonin‐mediated downregulation of ZNF746 suppresses bladder tumorigenesis mainly through inhibiting the AKT‐MMP‐9 signaling pathway , 2018, Journal of pineal research.

[15]  R. Reiter,et al.  Mitochondrial functions and melatonin: a tour of the reproductive cancers , 2018, Cellular and Molecular Life Sciences.

[16]  Yuqi Feng,et al.  Metabolic analysis of the melatonin biosynthesis pathway using chemical labeling coupled with liquid chromatography‐mass spectrometry , 2018, Journal of pineal research.

[17]  G. El-Sokkary,et al.  Melatonin inhibits breast cancer cell invasion through modulating DJ‐1/KLF17/ID‐1 signaling pathway , 2018, Journal of cellular biochemistry.

[18]  M. B. Arnao,et al.  Phytomelatonin, natural melatonin from plants as a novel dietary supplement: Sources, activities and world market , 2018, Journal of Functional Foods.

[19]  Wanli W. Smith,et al.  Regulation effects of melatonin on bone marrow mesenchymal stem cell differentiation , 2018, Journal of cellular physiology.

[20]  E. A. de Almeida,et al.  Evaluation of melatonin and AFMK levels in women with breast cancer , 2018, Endocrine.

[21]  R. Reiter,et al.  Melatonin increases brown adipose tissue mass and function in Zücker diabetic fatty rats: implications for obesity control , 2018, Journal of pineal research.

[22]  S. Arribas,et al.  Teas and herbal infusions as sources of melatonin and other bioactive non-nutrient components , 2018 .

[23]  M. B. Arnao,et al.  The Potential of Phytomelatonin as a Nutraceutical , 2018, Molecules.

[24]  Yu-lin Fang,et al.  Melatonin in grapes and grape-related foodstuffs: A review. , 2017, Food chemistry.

[25]  D. Kennaway Are the proposed benefits of melatonin-rich foods too hard to swallow? , 2017, Critical reviews in food science and nutrition.

[26]  R. Reiter,et al.  Melatonin and sirtuins: A “not‐so unexpected” relationship , 2017, Journal of pineal research.

[27]  N. Zisapel Paediatric use of melatonin: Letter to the Editor regarding the manuscript "Current role of melatonin in pediatric neurology:Clinical recommendations" by Bruni et al. Eur J Paediatr Neurol. 2015 Mar;19(2):122-33. , 2017, European journal of paediatric neurology : EJPN : official journal of the European Paediatric Neurology Society.

[28]  R. Reiter,et al.  Melatonin biosynthesis in plants: multiple pathways catalyze tryptophan to melatonin in the cytoplasm or chloroplasts , 2016, Journal of pineal research.

[29]  R. Reiter,et al.  Melatonin as an antioxidant: under promises but over delivers , 2016, Journal of pineal research.

[30]  R. Reiter,et al.  On the significance of an alternate pathway of melatonin synthesis via 5‐methoxytryptamine: comparisons across species , 2016, Journal of pineal research.

[31]  Weidong Huang,et al.  Effect of Cultivar, Temperature, and Environmental Conditions on the Dynamic Change of Melatonin in Mulberry Fruit Development and Wine Fermentation. , 2016, Journal of food science.

[32]  S. Arribas,et al.  Intake of bean sprouts influences melatonin and antioxidant capacity biomarker levels in rats. , 2016, Food & function.

[33]  A. M. Troncoso,et al.  Quality control and determination of melatonin in food supplements , 2016 .

[34]  R. Reiter,et al.  Melatonin: an ancient molecule that makes oxygen metabolically tolerable , 2015, Journal of pineal research.

[35]  R. Reiter,et al.  Predominance of 2‐hydroxymelatonin over melatonin in plants , 2015, Journal of pineal research.

[36]  Haijun Zhang,et al.  Roles of melatonin in abiotic stress resistance in plants. , 2015, Journal of experimental botany.

[37]  R. Liebana,et al.  Effect of illumination on the content of melatonin, phenolic compounds, and antioxidant activity during germination of lentils (Lens culinaris L.) and kidney beans (Phaseolus vulgaris L.). , 2014, Journal of agricultural and food chemistry.

[38]  D. Acuña-Castroviejo,et al.  Melatonin and metabolic regulation: a review. , 2014, Food & function.

[39]  R. Reiter,et al.  Fundamental Issues Related to the Origin of Melatonin and Melatonin Isomers during Evolution: Relation to Their Biological Functions , 2014, International journal of molecular sciences.

[40]  M. Wang,et al.  Melatonin from different fruit sources, functional roles, and analytical methods , 2014 .

[41]  K. Back,et al.  Melatonin synthesis in rice seedlings in vivo is enhanced at high temperatures and under dark conditions due to increased serotonin N‐acetyltransferase and N‐acetylserotonin methyltransferase activities , 2014, Journal of pineal research.

[42]  Yu Zhao,et al.  Changes in melatonin levels in transgenic ‘Micro‐Tom’ tomato overexpressing ovine AANAT and ovine HIOMT genes , 2014, Journal of pineal research.

[43]  E. Bozdag,et al.  Effects of caffeic acid phenethyl ester and melatonin on distraction osteogenesis: an experimental study , 2014, SpringerPlus.

[44]  Yu Zhao,et al.  Identification of genes for melatonin synthetic enzymes in ‘Red Fuji’ apple (Malus domestica Borkh.cv.Red) and their expression and melatonin production during fruit development , 2013, Journal of Pineal Research.

[45]  J. Johns,et al.  Determination of melatonin content in traditional Thai herbal remedies used as sleeping aids , 2013, DARU Journal of Pharmaceutical Sciences.

[46]  N. Johns,et al.  Serum melatonin levels and antioxidant capacities after consumption of pineapple, orange, or banana by healthy male volunteers , 2013, Journal of pineal research.

[47]  Yu Zhao,et al.  Melatonin and its potential biological functions in the fruits of sweet cherry , 2013, Journal of pineal research.

[48]  M. F. Silva,et al.  Analytical tools for elucidating the biological role of melatonin in plants by LC‐MS/MS , 2013, Electrophoresis.

[49]  L. Tanoue,et al.  Methods for staging non-small cell lung cancer: Diagnosis and management of lung cancer, 3rd ed: American College of Chest Physicians evidence-based clinical practice guidelines. , 2013, Chest.

[50]  M. Iriti,et al.  Melatonin, melatonin isomers and stilbenes in Italian traditional grape products and their antiradical capacity , 2013, Journal of pineal research.

[51]  R. Reiter,et al.  On the free radical scavenging activities of melatonin's metabolites, AFMK and AMK , 2013, Journal of pineal research.

[52]  N. Johns,et al.  Dietary intake of melatonin from tropical fruit altered urinary excretion of 6-sulfatoxymelatonin in healthy volunteers. , 2013, Journal of agricultural and food chemistry.

[53]  M. McHugh,et al.  Effect of tart cherry juice (Prunus cerasus) on melatonin levels and enhanced sleep quality , 2012, European Journal of Nutrition.

[54]  J. Calvo,et al.  High levels of melatonin generated during the brewing process , 2012, Journal of pineal research.

[55]  M. Raggi,et al.  Content of melatonin and other antioxidants in grape‐related foodstuffs: measurement using a MEPS‐HPLC‐F method , 2012, Journal of pineal research.

[56]  Jeanne M. Marrazzo,et al.  Bacterial Communities in Women with Bacterial Vaginosis: High Resolution Phylogenetic Analyses Reveal Relationships of Microbiota to Clinical Criteria , 2012, PloS one.

[57]  Gokare A. Ravishankar,et al.  Melatonin and serotonin profiles in beans ofCoffeaspecies: Melatonin and serotonin in beans ofCoffeaspp. , 2012 .

[58]  K. Back,et al.  Tryptamine 5‐hydroxylase‐deficient Sekiguchi rice induces synthesis of 5‐hydroxytryptophan and N‐acetyltryptamine but decreases melatonin biosynthesis during senescence process of detached leaves , 2012, Journal of pineal research.

[59]  S. Paredes,et al.  Urinary 6-sulfatoxymelatonin and total antioxidant capacity increase after the intake of a grape juice cv. Tempranillo stabilized with HHP. , 2012, Food & function.

[60]  M. C. García-Parrilla,et al.  Determination of the melatonin content of different varieties of tomatoes (Lycopersicon esculentum) and strawberries (Fragariaananassa). , 2011, Food chemistry.

[61]  Á. Gil-Izquierdo,et al.  Melatonin: A new bioactive compound in wine , 2011 .

[62]  G. Mazza,et al.  Application of LC and LC-MS to the Analysis of Melatonin and Serotonin in Edible Plants , 2011, Critical reviews in food science and nutrition.

[63]  L. Fuentes-Broto,et al.  Significance and application of melatonin in the regulation of brown adipose tissue metabolism: relation to human obesity , 2011, Obesity reviews : an official journal of the International Association for the Study of Obesity.

[64]  A. Rodriguez,et al.  Jerte Valley cherry-enriched diets improve nocturnal rest and increase 6-sulfatoxymelatonin and total antioxidant capacity in the urine of middle-aged and elderly humans. , 2010, The journals of gerontology. Series A, Biological sciences and medical sciences.

[65]  Germán A. Messina,et al.  Determination of melatonin in wine and plant extracts by capillary electrochromatography with immobilized carboxylic multi‐walled carbon nanotubes as stationary phase , 2010, Electrophoresis.

[66]  M. Perlis,et al.  Effects of a tart cherry juice beverage on the sleep of older adults with insomnia: a pilot study. , 2010, Journal of medicinal food.

[67]  R. Reiter,et al.  Melatonin, cardiolipin and mitochondrial bioenergetics in health and disease , 2010, Journal of pineal research.

[68]  P. Dandona,et al.  Macronutrient intake induces oxidative and inflammatory stress: potential relevance to atherosclerosis and insulin resistance , 2010, Experimental & Molecular Medicine.

[69]  J. Calvo,et al.  The perception that beer improves sleep onset might be a motivation for some to drink heavily. Is it only melatonin that matters? Reply to Dr. Molfino , 2010 .

[70]  Hyunseung Lee,et al.  Melatonin ameliorates cerulein‐induced pancreatitis by the modulation of nuclear erythroid 2‐related factor 2 and nuclear factor‐kappaB in rats , 2010, Journal of pineal research.

[71]  A. Rodriguez,et al.  A nutraceutical product based on Jerte Valley cherries improves sleep and augments the antioxidant status in humans , 2009 .

[72]  S. Bolling,et al.  Chemical profile and antioxidant capacities of tart cherry products , 2009 .

[73]  M. C. García-Parrilla,et al.  Analysis of melatonin in foods. , 2009 .

[74]  M. B. Arnao,et al.  Chemical stress by different agents affects the melatonin content of barley roots , 2009, Journal of pineal research.

[75]  H. Ezura,et al.  Profiling of melatonin in the model tomato (Solanum lycopersicum L.) cultivar Micro‐Tom , 2009, Journal of pineal research.

[76]  J. Calvo,et al.  Melatonin present in beer contributes to increase the levels of melatonin and antioxidant capacity of the human serum. , 2009, Clinical nutrition.

[77]  D. González-Gómez,et al.  Detection and quantification of melatonin and serotonin in eight Sweet Cherry cultivars (Prunus avium L.) , 2009 .

[78]  S. Caprio,et al.  Obesity in children and adolescents. , 2008, The Journal of clinical endocrinology and metabolism.

[79]  F. Marioni,et al.  A straightforward procedure to biosynthesise melatonin using freshly chopped Achillea millefolium L. as reagent , 2008 .

[80]  C. Nagata,et al.  Consumption of vegetables alters morning urinary 6‐sulfatoxymelatonin concentration , 2008, Journal of pineal research.

[81]  S. Paredes,et al.  The effect of tryptophan administration on the circadian rhythms of melatonin in plasma and the pineal gland of rats , 2008 .

[82]  N. Banik,et al.  Activation of calpain and caspase pathways in demyelination and neurodegeneration in animal model of multiple sclerosis. , 2008, CNS & neurological disorders drug targets.

[83]  E. Sribnick,et al.  Melatonin attenuates calpain upregulation, axonal damage and neuronal death in spinal cord injury in rats , 2008, Journal of pineal research.

[84]  M. Malaguti,et al.  HPLC-F analysis of melatonin and resveratrol isomers in wine using an SPE procedure. , 2008, Journal of separation science.

[85]  R. Reiter,et al.  Melatonin as a naturally occurring co‐substrate of quinone reductase‐2, the putative MT3 melatonin membrane receptor: hypothesis and significance , 2007, Journal of pineal research.

[86]  J. Després,et al.  International Day for the Evaluation of Abdominal Obesity (IDEA): A Study of Waist Circumference, Cardiovascular Disease, and Diabetes Mellitus in 168 000 Primary Care Patients in 63 Countries , 2007, Circulation.

[87]  T. Kozai,et al.  Melatonin in Glycyrrhiza uralensis: response of plant roots to spectral quality of light and UV‐B radiation , 2006, Journal of pineal research.

[88]  M. Iriti,et al.  Melatonin content in grape: myth or panacea? , 2006 .

[89]  S. V. Anisimov,et al.  Melatonin as antioxidant, geroprotector and anticarcinogen. , 2006, Biochimica et biophysica acta.

[90]  R. Reiter,et al.  Melatonin in walnuts: influence on levels of melatonin and total antioxidant capacity of blood. , 2005, Nutrition.

[91]  B. Bahr,et al.  Proteolysis of NR2B by calpain in the hippocampus of epileptic rats , 2005, NeuroReport.

[92]  K. Narayan,et al.  Obesity, metabolic syndrome, and type 2 diabetes: emerging epidemics and their cardiovascular implications. , 2004, Cardiology clinics.

[93]  S. Haffner,et al.  Does the metabolic syndrome improve identification of individuals at risk of type 2 diabetes and/or cardiovascular disease? , 2004, Diabetes care.

[94]  Vanesa Martín,et al.  Regulation of antioxidant enzymes: a significant role for melatonin , 2004, Journal of pineal research.

[95]  P. Renard,et al.  Melatonin reduces body weight gain in Sprague Dawley rats with diet-induced obesity. , 2003, Endocrinology.

[96]  A. Slominski,et al.  Characterization of the serotoninergic system in the C57BL/6 mouse skin. , 2003, European journal of biochemistry.

[97]  D. E. Goll,et al.  The calpain system. , 2003, Physiological reviews.

[98]  Yukui Zhang,et al.  Melatonin in Chinese medicinal herbs. , 2003, Life sciences.

[99]  R. Reiter,et al.  Melatonin: a hormone, a tissue factor, an autocoid, a paracoid, and an antioxidant vitamin , 2003, Journal of pineal research.

[100]  G. Bubenik REVIEW: Gastrointestinal Melatonin: Localization, Function, and Clinical Relevance , 2002, Digestive Diseases and Sciences.

[101]  S. Cuzzocrea,et al.  Effects of Melatonin Treatment in Septic Newborns , 2001, Pediatric Research.

[102]  P. Saxena,et al.  The role of serotonin and melatonin in plant morphogenesis: Regulation of auxin-induced root organogenesis in in vitro-cultured explants of st. John's Wort (Hypericum perforatum L.) , 2001, In Vitro Cellular & Developmental Biology - Plant.

[103]  R. Reiter,et al.  Detection and quantification of the antioxidant melatonin in Montmorency and Balaton tart cherries (Prunus cerasus). , 2001, Journal of agricultural and food chemistry.

[104]  R. Reiter,et al.  High levels of melatonin in the seeds of edible plants: possible function in germ tissue protection. , 2000, Life sciences.

[105]  P. Saxena,et al.  Tryptophan is a precursor for melatonin and serotonin biosynthesis in in vitro regenerated St. John's wort (Hypericum perforatum L. cv. Anthos) plants , 2000, Plant Cell Reports.

[106]  A. Matsumoto,et al.  Daily Melatonin Administration to Middle-Aged Male Rats Suppresses Body Weight, Intraabdominal Adiposity, and Plasma Leptin and Insulin Independent of Food Intake and Total Body Fat1. , 2000, Endocrinology.

[107]  T. Saido,et al.  A putative mechanism of demyelination in multiple sclerosis by a proteolytic enzyme, calpain. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[108]  A. Tomlinson,et al.  On-line HPLC-tandem mass spectrometry structural characterization of case-associated contaminants of L-tryptophan implicated with the onset of eosinophilia myalgia syndrome. , 1998, Toxicology letters.

[109]  R. Reiter Cytoprotective properties of melatonin: presumed association with oxidative damage and aging. , 1998, Nutrition.

[110]  A. Tomlinson,et al.  Structural characterization of contaminants found in commercial preparations of melatonin: similarities to case-related compounds from L-tryptophan associated with eosinophilia-myalgia syndrome. , 1998, Chemical research in toxicology.

[111]  P. Saxena,et al.  Melatonin in feverfew and other medicinal plants , 1997, The Lancet.

[112]  M. Baudry,et al.  Regional distribution and time-course of calpain activation following kainate-induced seizure activity in adult rat brain , 1996, Brain Research.

[113]  R. Reiter,et al.  Melatonin in edible plants identified by radioimmunoassay and by high performance liquid chromatography‐mass spectrometry , 1995, Journal of pineal research.

[114]  T B Shea,et al.  Calcium‐Activated Neutral Proteinase (Calpain) System in Aging and Alzheimer's Disease a , 1994, Annals of the New York Academy of Sciences.

[115]  G. Huether Melatonin Synthesis in the Gastrointestinal Tract and the Impact of Nutritional Factors on Circulating Melatonin , 1994, Annals of the New York Academy of Sciences.

[116]  R. Nixon,et al.  Widespread activation of calcium-activated neutral proteinase (calpain) in the brain in Alzheimer disease: a potential molecular basis for neuronal degeneration. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[117]  R. Reiter,et al.  Pineal melatonin: cell biology of its synthesis and of its physiological interactions. , 1991, Endocrine reviews.

[118]  G. Lynch,et al.  Distribution of calcium‐activated protease calpain in the rat brain , 1990, The Journal of comparative neurology.

[119]  A. Matus,et al.  Distribution of calpains I and II in rat brain , 1986, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[120]  H. Weissbach,et al.  Enzymatic O-Methylation of N-Acetylserotonin to Melatonin , 1960, Science.

[121]  A. Lerner,et al.  ISOLATION OF MELATONIN, THE PINEAL GLAND FACTOR THAT LIGHTENS MELANOCYTES1 , 1958 .

[122]  R. Reiter,et al.  Melatonin: A potential therapeutic agent against COVID-19 , 2021 .

[123]  M. B. Arnao,et al.  Phytomelatonin: Searching for Plants with High Levels for Use as a Natural Nutraceutical , 2015 .

[124]  R. Reiter,et al.  Functional roles of melatonin in plants, and perspectives in nutritional and agricultural science. , 2012, Journal of experimental botany.

[125]  M. Posmyk,et al.  Melatonin in plants , 2008, Acta Physiologiae Plantarum.

[126]  Josep M. Guerrero,et al.  Melatonin is a phytochemical in olive oil , 2007 .

[127]  D. Clarke,et al.  Melatonin and sleep disorders associated with intellectual disability: a clinical review. , 2007, Journal of intellectual disability research : JIDR.

[128]  Jan Nedergaard,et al.  Brown adipose tissue: function and physiological significance. , 2004, Physiological reviews.

[129]  F. Badria Melatonin, serotonin, and tryptamine in some egyptian food and medicinal plants. , 2002, Journal of medicinal food.

[130]  B. Poeggeler,et al.  Effect of tryptophan administration on circulating melatonin levels in chicks and rats: evidence for stimulation of melatonin synthesis and release in the gastrointestinal tract. , 1992, Life sciences.

[131]  H. Weissbach,et al.  Biosynthesis of melatonin: enzymic conversion of serotonin to N-acetylserotonin. , 1960, Biochimica et biophysica acta.