{"id":13443,"date":"2023-10-23T10:49:00","date_gmt":"2023-10-23T10:49:00","guid":{"rendered":"https:\/\/www.sygnaturediscovery.com\/?post_type=journal-paper&p=13443"},"modified":"2026-01-30T10:54:30","modified_gmt":"2026-01-30T10:54:30","slug":"melatonin-and-its-metabolites-can-serve-as-agonists-on-the-aryl-hydrocarbon-receptor-and-peroxisome-proliferator-activated-receptor-gamma","status":"publish","type":"journal-paper","link":"https:\/\/www.sygnaturediscovery.com\/fr\/journal-paper\/melatonin-and-its-metabolites-can-serve-as-agonists-on-the-aryl-hydrocarbon-receptor-and-peroxisome-proliferator-activated-receptor-gamma\/","title":{"rendered":"Melatonin and Its Metabolites Can Serve as Agonists on the Aryl Hydrocarbon Receptor and Peroxisome Proliferator-Activated Receptor Gamma"},"content":{"rendered":"\n

Andrzej T Slominski,\u00a0Tae-Kang Kim,\u00a0Radomir M Slominski,\u00a0Yuwei Song,\u00a0Shariq Qayyum,\u00a0Wojciech Placha,\u00a0Zorica Janjetovic,\u00a0Konrad Kleszczy\u0144ski,\u00a0Venkatram Atigadda,\u00a0Yuhua Song,\u00a0Chander Raman,\u00a0Cornelis J Elferink,\u00a0Judith Varady Hobrath<\/strong>,\u00a0Anton M Jetten,\u00a0Russel J Reiter<\/p>\n\n\n\n

Abstract<\/strong><\/p>\n\n\n\n

Melatonin is widely present in Nature. It has pleiotropic activities, in part mediated by interactions with high-affinity G-protein-coupled melatonin type 1 and 2 (MT1 and MT2) receptors or under extreme conditions, e.g., ischemia\/reperfusion. In pharmacological concentrations, it is given to counteract the massive damage caused by MT1- and MT2-independent mechanisms. The aryl hydrocarbon receptor (AhR) is a perfect candidate for mediating the latter effects because melatonin has structural similarity to its natural ligands, including tryptophan metabolites and indolic compounds. Using a cell-based Human AhR Reporter Assay System, we demonstrated that melatonin and its indolic and kynuric metabolites act as agonists on the AhR with EC50<\/sub>‘s between 10-4<\/sup> and 10-6<\/sup> M. This was further validated via the stimulation of the transcriptional activation of the CYP1A1<\/em> promoter. Furthermore, melatonin and its metabolites stimulated AhR translocation from the cytoplasm to the nucleus in human keratinocytes, as demonstrated by ImageStream II cytometry and Western blot (WB) analyses of cytoplasmic and nuclear fractions of human keratinocytes. These functional analyses are supported by in silico analyses. We also investigated the peroxisome proliferator-activated receptor (PPAR)\u03b3 as a potential target for melatonin and metabolites bioregulation. The binding studies using a TR-TFRET kit to assay the interaction of the ligand with the ligand-binding domain (LBD) of the PPAR\u03b3 showed agonistic activities of melatonin, 6-hydroxymelatonin and N<\/em>-acetyl-N<\/em>-formyl-5-methoxykynuramine with EC50<\/sub>‘s in the 10-4<\/sup> M range showing significantly lower affinities that those of rosiglitazone, e.g., a 10-8<\/sup> M range. These interactions were substantiated by stimulation of the luciferase activity of the construct containing PPARE by melatonin and its metabolites at 10-4<\/sup> M. As confirmed by the functional assays, binding mode predictions using a homology model of the AhR and a crystal structure of the PPAR\u03b3 suggest that melatonin and its metabolites, including 6-hydroxymelatonin, 5-methoxytryptamine and N<\/em>-acetyl-N<\/em>-formyl-5-methoxykynuramine, are excellent candidates to act on the AhR and PPAR\u03b3 with docking scores comparable to their corresponding natural ligands. Melatonin and its metabolites were modeled into the same ligand-binding pockets (LBDs) as their natural ligands. Thus, functional assays supported by molecular modeling have shown that melatonin and its indolic and kynuric metabolites can act as agonists on the AhR and they can interact with the PPAR\u03b3 at high concentrations. This provides a mechanistic explanation for previously reported cytoprotective actions of melatonin and its metabolites that require high local concentrations of the ligands to reduce cellular damage under elevated oxidative stress conditions. It also identifies these compounds as therapeutic agents to be used at pharmacological doses in the prevention or therapy of skin diseases.<\/p>\n\n\n\n

Ref: Int J Mol Sci 2023<\/a><\/p>\n","protected":false},"excerpt":{"rendered":"","protected":false},"featured_media":0,"template":"","category":[679],"resource_tag":[],"class_list":["post-13443","journal-paper","type-journal-paper","status-publish","hentry","category-computer-aided-drug-design"],"acf":[],"yoast_head":"\nMelatonin and Its Metabolites Can Serve as Agonists on the Aryl Hydrocarbon Receptor and Peroxisome Proliferator-Activated Receptor Gamma - Sygnature<\/title>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"https:\/\/www.sygnaturediscovery.com\/fr\/journal-paper\/melatonin-and-its-metabolites-can-serve-as-agonists-on-the-aryl-hydrocarbon-receptor-and-peroxisome-proliferator-activated-receptor-gamma\/\" \/>\n<meta property=\"og:locale\" content=\"fr_CA\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"Melatonin and Its Metabolites Can Serve as Agonists on the Aryl Hydrocarbon Receptor and Peroxisome Proliferator-Activated Receptor Gamma - Sygnature\" \/>\n<meta property=\"og:url\" content=\"https:\/\/www.sygnaturediscovery.com\/fr\/journal-paper\/melatonin-and-its-metabolites-can-serve-as-agonists-on-the-aryl-hydrocarbon-receptor-and-peroxisome-proliferator-activated-receptor-gamma\/\" \/>\n<meta property=\"og:site_name\" content=\"Sygnature\" \/>\n<meta property=\"article:modified_time\" content=\"2026-01-30T10:54:30+00:00\" \/>\n<meta property=\"og:image\" content=\"https:\/\/www.sygnaturediscovery.com\/wp-content\/uploads\/2026\/02\/sygnature-hit-to-lead-team-collaboration-scaled.webp\" \/>\n\t<meta property=\"og:image:width\" content=\"2560\" \/>\n\t<meta property=\"og:image:height\" content=\"1707\" \/>\n\t<meta property=\"og:image:type\" content=\"image\/webp\" \/>\n<meta name=\"twitter:card\" content=\"summary_large_image\" \/>\n<meta name=\"twitter:label1\" content=\"Estimation du temps de lecture\" \/>\n\t<meta name=\"twitter:data1\" content=\"3 minutes\" \/>\n<script type=\"application\/ld+json\" class=\"yoast-schema-graph\">{\"@context\":\"https:\\\/\\\/schema.org\",\"@graph\":[{\"@type\":\"WebPage\",\"@id\":\"https:\\\/\\\/www.sygnaturediscovery.com\\\/fr\\\/journal-paper\\\/melatonin-and-its-metabolites-can-serve-as-agonists-on-the-aryl-hydrocarbon-receptor-and-peroxisome-proliferator-activated-receptor-gamma\\\/\",\"url\":\"https:\\\/\\\/www.sygnaturediscovery.com\\\/fr\\\/journal-paper\\\/melatonin-and-its-metabolites-can-serve-as-agonists-on-the-aryl-hydrocarbon-receptor-and-peroxisome-proliferator-activated-receptor-gamma\\\/\",\"name\":\"Melatonin and Its Metabolites Can Serve as Agonists on the Aryl Hydrocarbon Receptor and Peroxisome Proliferator-Activated Receptor Gamma - Sygnature\",\"isPartOf\":{\"@id\":\"https:\\\/\\\/www.sygnaturediscovery.com\\\/fr\\\/#website\"},\"datePublished\":\"2023-10-23T10:49:00+00:00\",\"dateModified\":\"2026-01-30T10:54:30+00:00\",\"breadcrumb\":{\"@id\":\"https:\\\/\\\/www.sygnaturediscovery.com\\\/fr\\\/journal-paper\\\/melatonin-and-its-metabolites-can-serve-as-agonists-on-the-aryl-hydrocarbon-receptor-and-peroxisome-proliferator-activated-receptor-gamma\\\/#breadcrumb\"},\"inLanguage\":\"fr-CA\",\"potentialAction\":[{\"@type\":\"ReadAction\",\"target\":[\"https:\\\/\\\/www.sygnaturediscovery.com\\\/fr\\\/journal-paper\\\/melatonin-and-its-metabolites-can-serve-as-agonists-on-the-aryl-hydrocarbon-receptor-and-peroxisome-proliferator-activated-receptor-gamma\\\/\"]}]},{\"@type\":\"BreadcrumbList\",\"@id\":\"https:\\\/\\\/www.sygnaturediscovery.com\\\/fr\\\/journal-paper\\\/melatonin-and-its-metabolites-can-serve-as-agonists-on-the-aryl-hydrocarbon-receptor-and-peroxisome-proliferator-activated-receptor-gamma\\\/#breadcrumb\",\"itemListElement\":[{\"@type\":\"ListItem\",\"position\":1,\"name\":\"Home\",\"item\":\"https:\\\/\\\/www.sygnaturediscovery.com\\\/fr\\\/page-daccueil\\\/\"},{\"@type\":\"ListItem\",\"position\":2,\"name\":\"Melatonin and Its Metabolites Can Serve as Agonists on the Aryl Hydrocarbon Receptor and Peroxisome Proliferator-Activated Receptor Gamma\"}]},{\"@type\":\"WebSite\",\"@id\":\"https:\\\/\\\/www.sygnaturediscovery.com\\\/fr\\\/#website\",\"url\":\"https:\\\/\\\/www.sygnaturediscovery.com\\\/fr\\\/\",\"name\":\"Sygnature Discovery\",\"description\":\"\",\"publisher\":{\"@id\":\"https:\\\/\\\/www.sygnaturediscovery.com\\\/fr\\\/#organization\"},\"alternateName\":\"Sygnature\",\"potentialAction\":[{\"@type\":\"SearchAction\",\"target\":{\"@type\":\"EntryPoint\",\"urlTemplate\":\"https:\\\/\\\/www.sygnaturediscovery.com\\\/fr\\\/?s={search_term_string}\"},\"query-input\":{\"@type\":\"PropertyValueSpecification\",\"valueRequired\":true,\"valueName\":\"search_term_string\"}}],\"inLanguage\":\"fr-CA\"},{\"@type\":\"Organization\",\"@id\":\"https:\\\/\\\/www.sygnaturediscovery.com\\\/fr\\\/#organization\",\"name\":\"Sygnature\",\"url\":\"https:\\\/\\\/www.sygnaturediscovery.com\\\/fr\\\/\",\"logo\":{\"@type\":\"ImageObject\",\"inLanguage\":\"fr-CA\",\"@id\":\"https:\\\/\\\/www.sygnaturediscovery.com\\\/fr\\\/#\\\/schema\\\/logo\\\/image\\\/\",\"url\":\"https:\\\/\\\/www.sygnaturediscovery.com\\\/wp-content\\\/uploads\\\/2025\\\/11\\\/Logo.svg\",\"contentUrl\":\"https:\\\/\\\/www.sygnaturediscovery.com\\\/wp-content\\\/uploads\\\/2025\\\/11\\\/Logo.svg\",\"width\":1,\"height\":1,\"caption\":\"Sygnature\"},\"image\":{\"@id\":\"https:\\\/\\\/www.sygnaturediscovery.com\\\/fr\\\/#\\\/schema\\\/logo\\\/image\\\/\"}}]}<\/script>\n<!-- \/ Yoast SEO plugin. -->","yoast_head_json":{"title":"Melatonin and Its Metabolites Can Serve as Agonists on the Aryl Hydrocarbon Receptor and Peroxisome Proliferator-Activated Receptor Gamma - Sygnature","robots":{"index":"index","follow":"follow","max-snippet":"max-snippet:-1","max-image-preview":"max-image-preview:large","max-video-preview":"max-video-preview:-1"},"canonical":"https:\/\/www.sygnaturediscovery.com\/fr\/journal-paper\/melatonin-and-its-metabolites-can-serve-as-agonists-on-the-aryl-hydrocarbon-receptor-and-peroxisome-proliferator-activated-receptor-gamma\/","og_locale":"fr_CA","og_type":"article","og_title":"Melatonin and Its Metabolites Can Serve as Agonists on the Aryl Hydrocarbon Receptor and Peroxisome Proliferator-Activated Receptor Gamma - Sygnature","og_url":"https:\/\/www.sygnaturediscovery.com\/fr\/journal-paper\/melatonin-and-its-metabolites-can-serve-as-agonists-on-the-aryl-hydrocarbon-receptor-and-peroxisome-proliferator-activated-receptor-gamma\/","og_site_name":"Sygnature","article_modified_time":"2026-01-30T10:54:30+00:00","og_image":[{"width":2560,"height":1707,"url":"https:\/\/www.sygnaturediscovery.com\/wp-content\/uploads\/2026\/02\/sygnature-hit-to-lead-team-collaboration-scaled.webp","type":"image\/webp"}],"twitter_card":"summary_large_image","twitter_misc":{"Estimation du temps de lecture":"3 minutes"},"schema":{"@context":"https:\/\/schema.org","@graph":[{"@type":"WebPage","@id":"https:\/\/www.sygnaturediscovery.com\/fr\/journal-paper\/melatonin-and-its-metabolites-can-serve-as-agonists-on-the-aryl-hydrocarbon-receptor-and-peroxisome-proliferator-activated-receptor-gamma\/","url":"https:\/\/www.sygnaturediscovery.com\/fr\/journal-paper\/melatonin-and-its-metabolites-can-serve-as-agonists-on-the-aryl-hydrocarbon-receptor-and-peroxisome-proliferator-activated-receptor-gamma\/","name":"Melatonin and Its Metabolites Can Serve as Agonists on the Aryl Hydrocarbon Receptor and Peroxisome Proliferator-Activated Receptor Gamma - Sygnature","isPartOf":{"@id":"https:\/\/www.sygnaturediscovery.com\/fr\/#website"},"datePublished":"2023-10-23T10:49:00+00:00","dateModified":"2026-01-30T10:54:30+00:00","breadcrumb":{"@id":"https:\/\/www.sygnaturediscovery.com\/fr\/journal-paper\/melatonin-and-its-metabolites-can-serve-as-agonists-on-the-aryl-hydrocarbon-receptor-and-peroxisome-proliferator-activated-receptor-gamma\/#breadcrumb"},"inLanguage":"fr-CA","potentialAction":[{"@type":"ReadAction","target":["https:\/\/www.sygnaturediscovery.com\/fr\/journal-paper\/melatonin-and-its-metabolites-can-serve-as-agonists-on-the-aryl-hydrocarbon-receptor-and-peroxisome-proliferator-activated-receptor-gamma\/"]}]},{"@type":"BreadcrumbList","@id":"https:\/\/www.sygnaturediscovery.com\/fr\/journal-paper\/melatonin-and-its-metabolites-can-serve-as-agonists-on-the-aryl-hydrocarbon-receptor-and-peroxisome-proliferator-activated-receptor-gamma\/#breadcrumb","itemListElement":[{"@type":"ListItem","position":1,"name":"Home","item":"https:\/\/www.sygnaturediscovery.com\/fr\/page-daccueil\/"},{"@type":"ListItem","position":2,"name":"Melatonin and Its Metabolites Can Serve as Agonists on the Aryl Hydrocarbon Receptor and Peroxisome Proliferator-Activated Receptor Gamma"}]},{"@type":"WebSite","@id":"https:\/\/www.sygnaturediscovery.com\/fr\/#website","url":"https:\/\/www.sygnaturediscovery.com\/fr\/","name":"Sygnature Discovery","description":"","publisher":{"@id":"https:\/\/www.sygnaturediscovery.com\/fr\/#organization"},"alternateName":"Sygnature","potentialAction":[{"@type":"SearchAction","target":{"@type":"EntryPoint","urlTemplate":"https:\/\/www.sygnaturediscovery.com\/fr\/?s={search_term_string}"},"query-input":{"@type":"PropertyValueSpecification","valueRequired":true,"valueName":"search_term_string"}}],"inLanguage":"fr-CA"},{"@type":"Organization","@id":"https:\/\/www.sygnaturediscovery.com\/fr\/#organization","name":"Sygnature","url":"https:\/\/www.sygnaturediscovery.com\/fr\/","logo":{"@type":"ImageObject","inLanguage":"fr-CA","@id":"https:\/\/www.sygnaturediscovery.com\/fr\/#\/schema\/logo\/image\/","url":"https:\/\/www.sygnaturediscovery.com\/wp-content\/uploads\/2025\/11\/Logo.svg","contentUrl":"https:\/\/www.sygnaturediscovery.com\/wp-content\/uploads\/2025\/11\/Logo.svg","width":1,"height":1,"caption":"Sygnature"},"image":{"@id":"https:\/\/www.sygnaturediscovery.com\/fr\/#\/schema\/logo\/image\/"}}]}},"_links":{"self":[{"href":"https:\/\/www.sygnaturediscovery.com\/fr\/wp-json\/wp\/v2\/journal-paper\/13443","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.sygnaturediscovery.com\/fr\/wp-json\/wp\/v2\/journal-paper"}],"about":[{"href":"https:\/\/www.sygnaturediscovery.com\/fr\/wp-json\/wp\/v2\/types\/journal-paper"}],"version-history":[{"count":0,"href":"https:\/\/www.sygnaturediscovery.com\/fr\/wp-json\/wp\/v2\/journal-paper\/13443\/revisions"}],"wp:attachment":[{"href":"https:\/\/www.sygnaturediscovery.com\/fr\/wp-json\/wp\/v2\/media?parent=13443"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.sygnaturediscovery.com\/fr\/wp-json\/wp\/v2\/category?post=13443"},{"taxonomy":"resource_tag","embeddable":true,"href":"https:\/\/www.sygnaturediscovery.com\/fr\/wp-json\/wp\/v2\/resource_tag?post=13443"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}