{"schemaVersion":"wpf-profile-export-v1","exportedAt":"2026-09-18T15:30:54.630Z","profile":{"slug":"ghk-cu","name":"GHK-Cu","aliases":["Copper tripeptide-1","Gly-His-Lys copper complex","GHK copper","Prezatide copper"],"category":"Endogenous copper-binding peptide complex"},"synthesis":{"mechanism":"GHK-Cu is the copper(II) complex of the endogenous tripeptide glycyl-L-histidyl-L-lysine. It binds copper and has been studied in copper handling, extracellular-matrix remodeling, fibroblast activity, inflammatory signaling, antioxidant responses, and wound repair. Effects are formulation-, concentration-, route-, and model-dependent.","evidence":"The archive is rich in biochemical, cell, gene-expression, and animal work but sparse in rigorous human trials. Small or incompletely reported topical cosmetic studies provide signals, not proof. Preclinical findings do not validate injectable, systemic, anti-aging, hair-growth, or disease-treatment claims.","safety":"Topical cosmetic use does not establish the safety of compounded, injected, intranasal, or systemic GHK-Cu. Purity, copper content, sterility, dose, route, local reactions, sensitization, systemic copper exposure, interactions, and long-term safety remain important uncertainties.","observationalBoundary":"Governed corpus covering chemical identity, discovery, copper-binding mechanisms, skin-regeneration synthesis, gene-expression hypotheses, and animal wound models, with evidence lanes kept separate.","openQuestions":"Independent randomized human trials; standardized formulations; dose-response and tissue pharmacokinetics; long-term topical safety; systemic or injectable safety; reproducibility of gene-expression claims; and meaningful wound, skin, or hair outcomes."},"completion":{"version":"wpf-profile-v1.0","complete":false,"checks":[{"key":"overview","passed":true,"actual":336,"required":100,"severity":"blocking"},{"key":"evidence_summary","passed":true,"actual":308,"required":100,"severity":"blocking"},{"key":"safety_summary","passed":true,"actual":280,"required":100,"severity":"blocking"},{"key":"archive_boundary","passed":true,"actual":198,"required":75,"severity":"blocking"},{"key":"open_questions","passed":true,"actual":252,"required":75,"severity":"blocking"},{"key":"verified_sources","passed":true,"actual":25,"required":25,"severity":"blocking"},{"key":"reviewed_sources","passed":true,"actual":25,"required":1,"severity":"blocking"},{"key":"chemistry","passed":true,"actual":true,"required":true,"severity":"blocking"},{"key":"regulatory_context","passed":false,"actual":0,"required":2,"severity":"blocking"},{"key":"claims","passed":true,"actual":25,"required":1,"severity":"blocking"},{"key":"claim_traceability","passed":true,"actual":0,"required":0,"severity":"blocking"},{"key":"regulatory_freshness","passed":true,"actual":0,"required":0,"severity":"warning"}],"failures":["regulatory_context"]},"chemistry":{"id":"572dbd18d0b617edd3c1ede869d10e14","peptideId":"82d07ce3-167f-4019-b4f2-d802b3cba338","molecularFormula":"C14H22CuN6O4","molecularWeight":401.91,"aminoAcidSequence":"Gly-His-Lys","smiles":"C1=C(NC=N1)CC(C(=O)NC(CCCCN)C(=O)O)NC(=O)CN.[Cu]","inchi":"1S/C14H24N6O4.Cu/c15-4-2-1-3-10(14(23)24)20-13(22)11(19-12(21)6-16)5-9-7-17-8-18-9;/h7-8,10-11H,1-6,15-16H2,(H,17,18)(H,19,21)(H,20,22)(H,23,24);","inchikey":"DIWZQABMLHSNJR-UHFFFAOYSA-N","structureImageUrl":"https://pubchem.ncbi.nlm.nih.gov/image/imgsrv.fcgi?cid=378611&t=l","createdAt":"2026-09-08T18:31:47.338Z","updatedAt":"2026-09-08T18:31:47.338Z"},"evidence":[{"id":"8fed56b6668438829860683f89502221","peptideId":"82d07ce3-167f-4019-b4f2-d802b3cba338","title":"Glycyl-L-histidyl-L-lysine-Cu2+ (GHK-Cu) Attenuates CuSO4 or LPS induced-inflammation in Zebrafish larvae model.","sourceUrl":"https://pubmed.ncbi.nlm.nih.gov/41997403/","evidenceTier":"animal","summary":"Inflammation serves as a basic defense mechanism against both internal and external threats, while the unresolved or excessive inflammation can lead to irreversible tissue damage. Glycyl-L-histidyl-L-lysine-Cu2+ (GHK-Cu), a bioactive tripeptide complex known for its anti-aging and tissue repair properties, is extensively utilized in dermatological and hair care formulations. However, the role of GHK-Cu in regulating inflammation is less known. In this study, we explored the anti-inflammatory effects of GHK-Cu against the acute inflammation induced by copper sulfate (CuSO4) and lipopolysaccharide (LPS) in zebrafish larvae. GHK-Cu notably decreased the migration of neutrophils and...","authors":"Jing Hu, Chao Zhang, Feifei Wang","publishingOrg":null,"publicationYear":2026,"doi":"10.1016/j.ejphar.2026.178880","pubmedId":"41997403","jurisdiction":null,"dateAccessed":"2026-09-08T18:53:38.906Z","editorialNotes":"AI-assisted PubMed corpus expansion; owner authorized 2026-09-08.","sourceType":"peer_reviewed_research","claimSupported":"This source contributes animal_in_vivo evidence concerning Glycyl-L-histidyl-L-lysine-Cu2+ (GHK-Cu) Attenuates CuSO4 or LPS induced-inflammation in Zebrafish larvae model.","supportNature":"contextualizes","qualification":"Preclinical or mechanistic evidence does not establish human clinical efficacy, safe dose, route, or long-term safety.","verificationStatus":"verified","publicationStatus":"published","addedById":"0bf5b853-ea8b-4aa3-bffe-2af0fdd75150","machineActor":"wpf-five-corpus-expansion-2026-09-08","reviewedById":"0bf5b853-ea8b-4aa3-bffe-2af0fdd75150","canonicalSourceIdentity":"doi:10.1016/j.ejphar.2026.178880","sourceIdentityId":null,"sourceStatus":"active","sourceContentHash":null,"sourceVersion":1,"retrievedAt":"2026-09-08T18:53:38.906Z","retrievalProvider":"NCBI PubMed","retrievalPayloadRef":"wpf:ghk-cu:expansion:2026-09-08","evidenceLane":"animal_in_vivo","extractionPayload":{"limitations":["Preclinical or mechanistic evidence does not establish human clinical efficacy, safe dose, route, or long-term safety."],"studyDesign":"Preclinical experimental study","sourceStrength":{"grade":"B","score":65,"version":"WPF-ESR-1.0","dimensions":{"authority":18,"reporting":10,"directness":15,"replication":"review-sensitive","designAndBias":"publication-type-derived","populationRelevance":"lane-derived"},"provisional":true},"publicationTypes":["Journal Article"]},"provenancePayload":{"doi":"10.1016/j.ejphar.2026.178880","pmid":"41997403","retrievedFrom":"NCBI PubMed"},"validationGates":{"sourceVerified":true,"ownerAuthorized":true,"identityResolved":true,"neutralLanguageVerified":true},"engineState":"promoted_internal","engineRunId":null,"createdAt":"2026-09-08T18:53:38.906Z","updatedAt":"2026-09-08T18:53:38.906Z"},{"id":"1ef03f5d05b09dbe395e478e7b3f8162","peptideId":"82d07ce3-167f-4019-b4f2-d802b3cba338","title":"PubChem Compound Summary for CID 378611, GHK-Cu","sourceUrl":"https://pubchem.ncbi.nlm.nih.gov/compound/378611","evidenceTier":"laboratory","summary":"PubChem provides a chemical identity record for the copper complex of glycyl-L-histidyl-L-lysine, distinguishing it from uncomplexed GHK.","authors":null,"publishingOrg":null,"publicationYear":2026,"doi":null,"pubmedId":null,"jurisdiction":null,"dateAccessed":"2026-09-08T18:31:47.338Z","editorialNotes":"AI-assisted synthesis; owner-authorized governed publication 2026-09-08.","sourceType":"government_publication","claimSupported":"GHK-Cu is a defined copper complex of Gly-His-Lys.","supportNature":"contextualizes","qualification":"Chemical identity does not establish efficacy, safety, or approval.","verificationStatus":"verified","publicationStatus":"published","addedById":"0bf5b853-ea8b-4aa3-bffe-2af0fdd75150","machineActor":"wpf-reference-corpus-2026-09-08","reviewedById":"0bf5b853-ea8b-4aa3-bffe-2af0fdd75150","canonicalSourceIdentity":"url:https://pubchem.ncbi.nlm.nih.gov/compound/378611","sourceIdentityId":null,"sourceStatus":"active","sourceContentHash":null,"sourceVersion":1,"retrievedAt":"2026-09-08T18:31:47.338Z","retrievalProvider":"US government source","retrievalPayloadRef":"wpf:ghk-cu:reference-corpus:2026-09-08","evidenceLane":"mechanistic","extractionPayload":{"finding":"GHK-Cu is a defined copper complex of Gly-His-Lys.","population":"GHK-Cu chemical entity","sampleSize":null,"limitations":["Chemical identity does not establish efficacy, safety, or approval."],"studyDesign":"Curated chemical database record","sourceStrength":{"note":"Automated baseline based on evidence tier; full-text risk-of-bias review may revise it","grade":"D","score":48,"version":"WPF-ESR-1.0","provisional":true}},"provenancePayload":{"doi":null,"pmid":null,"reviewBatch":"ghk-cu-reference-corpus-2026-09-08"},"validationGates":{"sourceVerified":true,"ownerAuthorized":true,"identityResolved":true,"neutralLanguageVerified":true},"engineState":"promoted_internal","engineRunId":null,"createdAt":"2026-09-08T18:31:47.338Z","updatedAt":"2026-09-08T18:53:38.906Z"},{"id":"e22a7cef2859bde1111dcdc1e97b72f4","peptideId":"82d07ce3-167f-4019-b4f2-d802b3cba338","title":"Are We Ready to Measure Skin Permeation of Modern Antiaging GHK-Cu Tripeptide Encapsulated in Liposomes?","sourceUrl":"https://pubmed.ncbi.nlm.nih.gov/39795193/","evidenceTier":"insufficient","summary":"Cosmetically active compounds (CACs), both of lipophilic and hydrophilic origin, have difficulty reaching the deeper layers of the skin, and this shortcoming significantly reduces their efficacy. One such CAC that occurs naturally in the human body and displays many beneficial properties (via reducing fine lines and wrinkles, tightening skin, improving its elasticity, etc.) is the glycyl-L-histidyl-L-lysine tripeptide complex of copper (GHK-Cu). GHK-Cu is a fairly hydrophilic compound with limited permeation through the lipophilic stratum corneum. On the other hand, liposomes capable of encapsulating GHK-Cu may improve its permeation potential. The present review discusses various issues...","authors":"Karolina Ogórek, Kinga Nowak, Emilia Wadych, Lena Ruzik, Andrei R Timerbaev, Magdalena Matczuk","publishingOrg":null,"publicationYear":2025,"doi":"10.3390/molecules30010136","pubmedId":"39795193","jurisdiction":null,"dateAccessed":"2026-09-08T18:53:38.906Z","editorialNotes":"AI-assisted PubMed corpus expansion; owner authorized 2026-09-08.","sourceType":"systematic_review_or_meta_analysis","claimSupported":"This source contributes systematic_review evidence concerning Are We Ready to Measure Skin Permeation of Modern Antiaging GHK-Cu Tripeptide Encapsulated in Liposomes?","supportNature":"contextualizes","qualification":"Narrative synthesis; conclusions depend on source selection and do not substitute for primary clinical evidence.","verificationStatus":"verified","publicationStatus":"published","addedById":"0bf5b853-ea8b-4aa3-bffe-2af0fdd75150","machineActor":"wpf-five-corpus-expansion-2026-09-08","reviewedById":"0bf5b853-ea8b-4aa3-bffe-2af0fdd75150","canonicalSourceIdentity":"doi:10.3390/molecules30010136","sourceIdentityId":null,"sourceStatus":"active","sourceContentHash":null,"sourceVersion":1,"retrievedAt":"2026-09-08T18:53:38.906Z","retrievalProvider":"NCBI PubMed","retrievalPayloadRef":"wpf:ghk-cu:expansion:2026-09-08","evidenceLane":"systematic_review","extractionPayload":{"limitations":["Narrative synthesis; conclusions depend on source selection and do not substitute for primary clinical evidence."],"studyDesign":"Narrative review","sourceStrength":{"grade":"B","score":68,"version":"WPF-ESR-1.0","dimensions":{"authority":18,"reporting":10,"directness":15,"replication":"review-sensitive","designAndBias":"publication-type-derived","populationRelevance":"lane-derived"},"provisional":true},"publicationTypes":["Journal Article","Review"]},"provenancePayload":{"doi":"10.3390/molecules30010136","pmid":"39795193","retrievedFrom":"NCBI PubMed"},"validationGates":{"sourceVerified":true,"ownerAuthorized":true,"identityResolved":true,"neutralLanguageVerified":true},"engineState":"promoted_internal","engineRunId":null,"createdAt":"2026-09-08T18:53:38.906Z","updatedAt":"2026-09-08T18:53:38.906Z"},{"id":"de8ea06a5505868f17ddafa70ae72c90","peptideId":"82d07ce3-167f-4019-b4f2-d802b3cba338","title":"Copper Complexes with New Glycyl-l-histidyl-l-lysine-Hyaluronan Conjugates Show Antioxidant Properties and Osteogenic and Angiogenic Synergistic Effects.","sourceUrl":"https://pubmed.ncbi.nlm.nih.gov/40123442/","evidenceTier":"laboratory","summary":"In recent years, hyaluronic acid (HA) and the natural tripeptide glycyl-l-histidyl-l-lysine (GHK), especially its copper(II) complex (GHK-Cu), individually have been shown to exert helpful properties for bone protection and regeneration. However, they are not strong enough to handle oxidative stress, hydrolytic attack, or environmental conditions. Being aware that conjugation chemistry has recently emerged as an appealing approach for generating new molecular entities capable of preserving the molecular integrity of their moieties or delaying their degradation, herein we present the synthesis of conjugates of HA with GHK (GHK-HA), at different loadings of the tripeptide. GHK-HA binds...","authors":"Valentina Greco, Valeria Lanza, Barbara Tomasello, Irina Naletova, Warren R L Cairns, Sebastiano Sciuto, Enrico Rizzarelli","publishingOrg":null,"publicationYear":2025,"doi":"10.1021/acs.bioconjchem.4c00545","pubmedId":"40123442","jurisdiction":null,"dateAccessed":"2026-09-08T18:53:38.906Z","editorialNotes":"AI-assisted PubMed corpus expansion; owner authorized 2026-09-08.","sourceType":"peer_reviewed_research","claimSupported":"This source contributes in_vitro evidence concerning Copper Complexes with New Glycyl-l-histidyl-l-lysine-Hyaluronan Conjugates Show Antioxidant Properties and Osteogenic and Angiogenic Synergistic Effects.","supportNature":"contextualizes","qualification":"Preclinical or mechanistic evidence does not establish human clinical efficacy, safe dose, route, or long-term safety.","verificationStatus":"verified","publicationStatus":"published","addedById":"0bf5b853-ea8b-4aa3-bffe-2af0fdd75150","machineActor":"wpf-five-corpus-expansion-2026-09-08","reviewedById":"0bf5b853-ea8b-4aa3-bffe-2af0fdd75150","canonicalSourceIdentity":"doi:10.1021/acs.bioconjchem.4c00545","sourceIdentityId":null,"sourceStatus":"active","sourceContentHash":null,"sourceVersion":1,"retrievedAt":"2026-09-08T18:53:38.906Z","retrievalProvider":"NCBI PubMed","retrievalPayloadRef":"wpf:ghk-cu:expansion:2026-09-08","evidenceLane":"in_vitro","extractionPayload":{"limitations":["Preclinical or mechanistic evidence does not establish human clinical efficacy, safe dose, route, or long-term safety."],"studyDesign":"Preclinical experimental study","sourceStrength":{"grade":"B","score":65,"version":"WPF-ESR-1.0","dimensions":{"authority":18,"reporting":10,"directness":15,"replication":"review-sensitive","designAndBias":"publication-type-derived","populationRelevance":"lane-derived"},"provisional":true},"publicationTypes":["Journal Article","Research Support, Non-U.S. Gov't"]},"provenancePayload":{"doi":"10.1021/acs.bioconjchem.4c00545","pmid":"40123442","retrievedFrom":"NCBI PubMed"},"validationGates":{"sourceVerified":true,"ownerAuthorized":true,"identityResolved":true,"neutralLanguageVerified":true},"engineState":"promoted_internal","engineRunId":null,"createdAt":"2026-09-08T18:53:38.906Z","updatedAt":"2026-09-08T18:53:38.906Z"},{"id":"26125691eb3361cd87163bb8221a5787","peptideId":"82d07ce3-167f-4019-b4f2-d802b3cba338","title":"Topically applied GHK as an anti-wrinkle peptide: Advantages, problems and prospective.","sourceUrl":"https://pubmed.ncbi.nlm.nih.gov/39963574/","evidenceTier":"insufficient","summary":"Peptides are promising and attractive anti-wrinkle active ingredients, amongst which glycyl-histidyl-lysine peptide (GHK) is one of the most broadly promoted peptide for topical application. This simple sequence of amino acid residues not only has the capability of tissue regeneration and the enhancement of collagen and glycosaminoglycans synthesis but also is able to increase nerve outgrowth and angiogenesis. Consequently, GHK has several properties, from wound healing to prevention/reduction wrinkles. GHK-Cu and Pal-GHK are metal complex and palmitoylated derivatives of GHK, respectively. Although GHK-Cu and Pal-GHK are widely used in anti-wrinkle products available on the cosmetic...","authors":"Seyedeh Maryam Mortazavi, Seyyed Ali Mohammadi Vadoud, Hamid Reza Moghimi","publishingOrg":null,"publicationYear":2025,"doi":"10.34172/bi.30071","pubmedId":"39963574","jurisdiction":null,"dateAccessed":"2026-09-08T18:53:38.906Z","editorialNotes":"AI-assisted PubMed corpus expansion; owner authorized 2026-09-08.","sourceType":"systematic_review_or_meta_analysis","claimSupported":"This source contributes systematic_review evidence concerning Topically applied GHK as an anti-wrinkle peptide: Advantages, problems and prospective.","supportNature":"contextualizes","qualification":"Narrative synthesis; conclusions depend on source selection and do not substitute for primary clinical evidence.","verificationStatus":"verified","publicationStatus":"published","addedById":"0bf5b853-ea8b-4aa3-bffe-2af0fdd75150","machineActor":"wpf-five-corpus-expansion-2026-09-08","reviewedById":"0bf5b853-ea8b-4aa3-bffe-2af0fdd75150","canonicalSourceIdentity":"doi:10.34172/bi.30071","sourceIdentityId":null,"sourceStatus":"active","sourceContentHash":null,"sourceVersion":1,"retrievedAt":"2026-09-08T18:53:38.906Z","retrievalProvider":"NCBI PubMed","retrievalPayloadRef":"wpf:ghk-cu:expansion:2026-09-08","evidenceLane":"systematic_review","extractionPayload":{"limitations":["Narrative synthesis; conclusions depend on source selection and do not substitute for primary clinical evidence."],"studyDesign":"Narrative review","sourceStrength":{"grade":"B","score":68,"version":"WPF-ESR-1.0","dimensions":{"authority":18,"reporting":10,"directness":15,"replication":"review-sensitive","designAndBias":"publication-type-derived","populationRelevance":"lane-derived"},"provisional":true},"publicationTypes":["Journal Article","Review"]},"provenancePayload":{"doi":"10.34172/bi.30071","pmid":"39963574","retrievedFrom":"NCBI PubMed"},"validationGates":{"sourceVerified":true,"ownerAuthorized":true,"identityResolved":true,"neutralLanguageVerified":true},"engineState":"promoted_internal","engineRunId":null,"createdAt":"2026-09-08T18:53:38.906Z","updatedAt":"2026-09-08T18:53:38.906Z"},{"id":"b4f3d19ac829882734dd9bc92462b3ee","peptideId":"82d07ce3-167f-4019-b4f2-d802b3cba338","title":"The glycyl-l-histidyl-l-lysine-Cu2+ tripeptide complex attenuates lung inflammation and fibrosis in silicosis by targeting peroxiredoxin 6.","sourceUrl":"https://pubmed.ncbi.nlm.nih.gov/38879894/","evidenceTier":"animal","summary":"Silicosis is the most common type of pneumoconiosis, having a high incidence in workers chronically exposed to crystalline silica (CS). No specific medication exists for this condition. GHK, a tripeptide naturally occurring in human blood and urine, has antioxidant effects. We aimed to investigate the therapeutic effect of GHK-Cu on silicosis and its potential underlying molecular mechanism. An experimental silicosis mouse model was established to observe the effects of GHK-Cu on lung inflammation and fibrosis. Moreover, the effects of GHK-Cu on the alveolar macrophages (AM) were examined using the RAW264.7 cell line. Its molecular target, peroxiredoxin 6 (PRDX6), has been identified,...","authors":"Yiding Bian, Mingming Deng, Jia Liu, Jiaye Li, Qin Zhang, Zilin Wang, Liwei Liao, Jinrui Miao","publishingOrg":null,"publicationYear":2024,"doi":"10.1016/j.redox.2024.103237","pubmedId":"38879894","jurisdiction":null,"dateAccessed":"2026-09-08T18:53:38.906Z","editorialNotes":"AI-assisted PubMed corpus expansion; owner authorized 2026-09-08.","sourceType":"peer_reviewed_research","claimSupported":"This source contributes animal_in_vivo evidence concerning The glycyl-l-histidyl-l-lysine-Cu2+ tripeptide complex attenuates lung inflammation and fibrosis in silicosis by targeting peroxiredoxin 6.","supportNature":"contextualizes","qualification":"Preclinical or mechanistic evidence does not establish human clinical efficacy, safe dose, route, or long-term safety.","verificationStatus":"verified","publicationStatus":"published","addedById":"0bf5b853-ea8b-4aa3-bffe-2af0fdd75150","machineActor":"wpf-five-corpus-expansion-2026-09-08","reviewedById":"0bf5b853-ea8b-4aa3-bffe-2af0fdd75150","canonicalSourceIdentity":"doi:10.1016/j.redox.2024.103237","sourceIdentityId":null,"sourceStatus":"active","sourceContentHash":null,"sourceVersion":1,"retrievedAt":"2026-09-08T18:53:38.906Z","retrievalProvider":"NCBI PubMed","retrievalPayloadRef":"wpf:ghk-cu:expansion:2026-09-08","evidenceLane":"animal_in_vivo","extractionPayload":{"limitations":["Preclinical or mechanistic evidence does not establish human clinical efficacy, safe dose, route, or long-term safety."],"studyDesign":"Preclinical experimental study","sourceStrength":{"grade":"B","score":65,"version":"WPF-ESR-1.0","dimensions":{"authority":18,"reporting":10,"directness":15,"replication":"review-sensitive","designAndBias":"publication-type-derived","populationRelevance":"lane-derived"},"provisional":true},"publicationTypes":["Journal Article"]},"provenancePayload":{"doi":"10.1016/j.redox.2024.103237","pmid":"38879894","retrievedFrom":"NCBI PubMed"},"validationGates":{"sourceVerified":true,"ownerAuthorized":true,"identityResolved":true,"neutralLanguageVerified":true},"engineState":"promoted_internal","engineRunId":null,"createdAt":"2026-09-08T18:53:38.906Z","updatedAt":"2026-09-08T18:53:38.906Z"},{"id":"1ed2ddcc2e34afd9f08ad306960f2f4f","peptideId":"82d07ce3-167f-4019-b4f2-d802b3cba338","title":"Glycyl-l-histidyl-l-lysine-Cu2+ rescues cigarette smoking-induced skeletal muscle dysfunction via a sirtuin 1-dependent pathway.","sourceUrl":"https://pubmed.ncbi.nlm.nih.gov/36905132/","evidenceTier":"animal","summary":"Skeletal muscle dysfunction is an important co-morbidity in patients with chronic obstructive pulmonary disease (COPD) and is significantly associated with increased mortality. Oxidative stress has been demonstrated an important trigger for COPD-related skeletal muscle dysfunction. Glycine-histidine-lysine (GHK) is an active tripeptide, which is a normal component of human plasma, saliva, and urine; promotes tissue regeneration; and acts as an anti-inflammatory and antioxidant properties. The purpose of this study was to determine whether GHK is involved in COPD-related skeletal muscle dysfunction. The plasma GHK level in patients with COPD (n = 9) and age-paired healthy subjects (n =...","authors":"Mingming Deng, Qin Zhang, Liming Yan, Yiding Bian, Ruixia Li, Jinghan Gao, Yingxi Wang, Jinrui Miao","publishingOrg":null,"publicationYear":2023,"doi":"10.1002/jcsm.13213","pubmedId":"36905132","jurisdiction":null,"dateAccessed":"2026-09-08T18:53:38.906Z","editorialNotes":"AI-assisted PubMed corpus expansion; owner authorized 2026-09-08.","sourceType":"peer_reviewed_research","claimSupported":"This source contributes animal_in_vivo evidence concerning Glycyl-l-histidyl-l-lysine-Cu2+ rescues cigarette smoking-induced skeletal muscle dysfunction via a sirtuin 1-dependent pathway.","supportNature":"contextualizes","qualification":"Preclinical or mechanistic evidence does not establish human clinical efficacy, safe dose, route, or long-term safety.","verificationStatus":"verified","publicationStatus":"published","addedById":"0bf5b853-ea8b-4aa3-bffe-2af0fdd75150","machineActor":"wpf-five-corpus-expansion-2026-09-08","reviewedById":"0bf5b853-ea8b-4aa3-bffe-2af0fdd75150","canonicalSourceIdentity":"doi:10.1002/jcsm.13213","sourceIdentityId":null,"sourceStatus":"active","sourceContentHash":null,"sourceVersion":1,"retrievedAt":"2026-09-08T18:53:38.906Z","retrievalProvider":"NCBI PubMed","retrievalPayloadRef":"wpf:ghk-cu:expansion:2026-09-08","evidenceLane":"animal_in_vivo","extractionPayload":{"limitations":["Preclinical or mechanistic evidence does not establish human clinical efficacy, safe dose, route, or long-term safety."],"studyDesign":"Preclinical experimental study","sourceStrength":{"grade":"B","score":65,"version":"WPF-ESR-1.0","dimensions":{"authority":18,"reporting":10,"directness":15,"replication":"review-sensitive","designAndBias":"publication-type-derived","populationRelevance":"lane-derived"},"provisional":true},"publicationTypes":["Journal Article","Research Support, Non-U.S. Gov't"]},"provenancePayload":{"doi":"10.1002/jcsm.13213","pmid":"36905132","retrievedFrom":"NCBI PubMed"},"validationGates":{"sourceVerified":true,"ownerAuthorized":true,"identityResolved":true,"neutralLanguageVerified":true},"engineState":"promoted_internal","engineRunId":null,"createdAt":"2026-09-08T18:53:38.906Z","updatedAt":"2026-09-08T18:53:38.906Z"},{"id":"a7da463aaf3c15d5ac1d89931930d3fb","peptideId":"82d07ce3-167f-4019-b4f2-d802b3cba338","title":"Relief of ovalbumin-induced airway remodeling by the glycyl-l-histidyl-l-lysine-Cu2+ tripeptide complex via activation of SIRT1 in airway epithelial cells.","sourceUrl":"https://pubmed.ncbi.nlm.nih.gov/37257226/","evidenceTier":"animal","summary":"Fixed airflow limitation (FAO), prevalent in patients with severe or difficult-to-treat asthma, is mainly caused by airway remodeling. Airway remodeling is initiated by inflammation and involves subsequent pathological changes. Glycyl-l-histidyl-l-lysine (GHK) is a matrikine with anti-inflammatory and antioxidant effects, naturally existing in human tissue. At present, the GHK level in human plasma and whether it is related to airway remodeling of asthma remain unclear. This study was conducted to determine how GHK is involved in airway remodeling in asthma. Our result showed that the plasma GHK levels of patients with asthma were significantly lower than those of age-matched healthy...","authors":"Qin Zhang, Jia Liu, Ming-Ming Deng, Run Tong, Gang Hou","publishingOrg":null,"publicationYear":2023,"doi":"10.1016/j.biopha.2023.114936","pubmedId":"37257226","jurisdiction":null,"dateAccessed":"2026-09-08T18:53:38.906Z","editorialNotes":"AI-assisted PubMed corpus expansion; owner authorized 2026-09-08.","sourceType":"peer_reviewed_research","claimSupported":"This source contributes animal_in_vivo evidence concerning Relief of ovalbumin-induced airway remodeling by the glycyl-l-histidyl-l-lysine-Cu2+ tripeptide complex via activation of SIRT1 in airway epithelial cells.","supportNature":"contextualizes","qualification":"Preclinical or mechanistic evidence does not establish human clinical efficacy, safe dose, route, or long-term safety.","verificationStatus":"verified","publicationStatus":"published","addedById":"0bf5b853-ea8b-4aa3-bffe-2af0fdd75150","machineActor":"wpf-five-corpus-expansion-2026-09-08","reviewedById":"0bf5b853-ea8b-4aa3-bffe-2af0fdd75150","canonicalSourceIdentity":"doi:10.1016/j.biopha.2023.114936","sourceIdentityId":null,"sourceStatus":"active","sourceContentHash":null,"sourceVersion":1,"retrievedAt":"2026-09-08T18:53:38.906Z","retrievalProvider":"NCBI PubMed","retrievalPayloadRef":"wpf:ghk-cu:expansion:2026-09-08","evidenceLane":"animal_in_vivo","extractionPayload":{"limitations":["Preclinical or mechanistic evidence does not establish human clinical efficacy, safe dose, route, or long-term safety."],"studyDesign":"Preclinical experimental study","sourceStrength":{"grade":"B","score":65,"version":"WPF-ESR-1.0","dimensions":{"authority":18,"reporting":10,"directness":15,"replication":"review-sensitive","designAndBias":"publication-type-derived","populationRelevance":"lane-derived"},"provisional":true},"publicationTypes":["Journal Article"]},"provenancePayload":{"doi":"10.1016/j.biopha.2023.114936","pmid":"37257226","retrievedFrom":"NCBI PubMed"},"validationGates":{"sourceVerified":true,"ownerAuthorized":true,"identityResolved":true,"neutralLanguageVerified":true},"engineState":"promoted_internal","engineRunId":null,"createdAt":"2026-09-08T18:53:38.906Z","updatedAt":"2026-09-08T18:53:38.906Z"},{"id":"75af817fa2f417a0b77ed69275340668","peptideId":"82d07ce3-167f-4019-b4f2-d802b3cba338","title":"Glycyl-L-histidyl-L-lysine-Cu2+ attenuates cigarette smoke-induced pulmonary emphysema and inflammation by reducing oxidative stress pathway.","sourceUrl":"https://pubmed.ncbi.nlm.nih.gov/35936787/","evidenceTier":"animal","summary":"Background: Chronic obstructive pulmonary disease (COPD) is a common respiratory disorder manifested as chronic airway inflammation and persistent airflow limitation with the essential mechanism as inflammatory response and oxidative stress induced by toxic exposures such as cigarette smoke (CS). Glycyl-L-histidyl-L-lysine (GHK) is a nontoxic tripeptide involved in the process of healing and regeneration as a natural product. With the combination of Cu(II), glycyl-L-histidyl-L-lysine-Cu2+ (GHK-Cu) improves antioxidative and anti-inflammatory bioavailability, and they might offer potential therapeutic properties for COPD. Thus, the present study aimed to identify the potential effects of...","authors":"Qin Zhang, Liming Yan, Jingwen Lu, Xiaoming Zhou","publishingOrg":null,"publicationYear":2022,"doi":"10.3389/fmolb.2022.925700","pubmedId":"35936787","jurisdiction":null,"dateAccessed":"2026-09-08T18:53:38.906Z","editorialNotes":"AI-assisted PubMed corpus expansion; owner authorized 2026-09-08.","sourceType":"peer_reviewed_research","claimSupported":"This source contributes animal_in_vivo evidence concerning Glycyl-L-histidyl-L-lysine-Cu2+ attenuates cigarette smoke-induced pulmonary emphysema and inflammation by reducing oxidative stress pathway.","supportNature":"contextualizes","qualification":"Preclinical or mechanistic evidence does not establish human clinical efficacy, safe dose, route, or long-term safety.","verificationStatus":"verified","publicationStatus":"published","addedById":"0bf5b853-ea8b-4aa3-bffe-2af0fdd75150","machineActor":"wpf-five-corpus-expansion-2026-09-08","reviewedById":"0bf5b853-ea8b-4aa3-bffe-2af0fdd75150","canonicalSourceIdentity":"doi:10.3389/fmolb.2022.925700","sourceIdentityId":null,"sourceStatus":"active","sourceContentHash":null,"sourceVersion":1,"retrievedAt":"2026-09-08T18:53:38.906Z","retrievalProvider":"NCBI PubMed","retrievalPayloadRef":"wpf:ghk-cu:expansion:2026-09-08","evidenceLane":"animal_in_vivo","extractionPayload":{"limitations":["Preclinical or mechanistic evidence does not establish human clinical efficacy, safe dose, route, or long-term safety."],"studyDesign":"Preclinical experimental study","sourceStrength":{"grade":"B","score":65,"version":"WPF-ESR-1.0","dimensions":{"authority":18,"reporting":10,"directness":15,"replication":"review-sensitive","designAndBias":"publication-type-derived","populationRelevance":"lane-derived"},"provisional":true},"publicationTypes":["Journal Article"]},"provenancePayload":{"doi":"10.3389/fmolb.2022.925700","pmid":"35936787","retrievedFrom":"NCBI PubMed"},"validationGates":{"sourceVerified":true,"ownerAuthorized":true,"identityResolved":true,"neutralLanguageVerified":true},"engineState":"promoted_internal","engineRunId":null,"createdAt":"2026-09-08T18:53:38.906Z","updatedAt":"2026-09-08T18:53:38.906Z"},{"id":"889187d2ab32569209d90428af1debe6","peptideId":"82d07ce3-167f-4019-b4f2-d802b3cba338","title":"Copper-tripeptides (cuzymes) with peroxidase-mimetic activity.","sourceUrl":"https://pubmed.ncbi.nlm.nih.gov/35515638/","evidenceTier":"laboratory","summary":"Peroxidases are enzymes that use hydrogen peroxide to oxidize substrates such as 2,2-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ATBS). In this study, we showed that copper-tripeptide complexes (\"cuzymes\") also exhibited peroxidase-like activities. Different cuzymes could be formed by using various tripeptide ligands, such as GGG, GGH or HGG. However, the peroxidase-like activity of cuzymes depends on the sequence of the tripeptide (Cu-GGG > Cu-HGG > Cu-GGH). When ABTS was used as the substrate, the activity of Cu-GGG was 326 ± 1.5 U mg-1 which was 2.5 times higher than that of horseradish peroxidase (HRP). Copper-tripeptide complexes were also used to degrade trypan blue dye. By...","authors":"Le Truc Nguyen, Wing Fat Ho, Kun-Lin Yang","publishingOrg":null,"publicationYear":2020,"doi":"10.1039/d0ra02472d","pubmedId":"35515638","jurisdiction":null,"dateAccessed":"2026-09-08T18:53:38.906Z","editorialNotes":"AI-assisted PubMed corpus expansion; owner authorized 2026-09-08.","sourceType":"peer_reviewed_research","claimSupported":"This source contributes mechanistic evidence concerning Copper-tripeptides (cuzymes) with peroxidase-mimetic activity.","supportNature":"contextualizes","qualification":"Preclinical or mechanistic evidence does not establish human clinical efficacy, safe dose, route, or long-term safety.","verificationStatus":"verified","publicationStatus":"published","addedById":"0bf5b853-ea8b-4aa3-bffe-2af0fdd75150","machineActor":"wpf-five-corpus-expansion-2026-09-08","reviewedById":"0bf5b853-ea8b-4aa3-bffe-2af0fdd75150","canonicalSourceIdentity":"doi:10.1039/d0ra02472d","sourceIdentityId":null,"sourceStatus":"active","sourceContentHash":null,"sourceVersion":1,"retrievedAt":"2026-09-08T18:53:38.906Z","retrievalProvider":"NCBI PubMed","retrievalPayloadRef":"wpf:ghk-cu:expansion:2026-09-08","evidenceLane":"mechanistic","extractionPayload":{"limitations":["Preclinical or mechanistic evidence does not establish human clinical efficacy, safe dose, route, or long-term safety."],"studyDesign":"Preclinical experimental study","sourceStrength":{"grade":"B","score":65,"version":"WPF-ESR-1.0","dimensions":{"authority":18,"reporting":10,"directness":15,"replication":"review-sensitive","designAndBias":"publication-type-derived","populationRelevance":"lane-derived"},"provisional":true},"publicationTypes":["Journal Article"]},"provenancePayload":{"doi":"10.1039/d0ra02472d","pmid":"35515638","retrievedFrom":"NCBI PubMed"},"validationGates":{"sourceVerified":true,"ownerAuthorized":true,"identityResolved":true,"neutralLanguageVerified":true},"engineState":"promoted_internal","engineRunId":null,"createdAt":"2026-09-08T18:53:38.906Z","updatedAt":"2026-09-08T18:53:38.906Z"},{"id":"7efa3539dea6d6ff62d881f94db05f16","peptideId":"82d07ce3-167f-4019-b4f2-d802b3cba338","title":"The potential of GHK as an anti-aging peptide.","sourceUrl":"https://pubmed.ncbi.nlm.nih.gov/35083444/","evidenceTier":"animal","summary":"GHK (glycyl-L-histidyl-L-lysine) is a naturally occurring peptide found in human serum with levels averaging 200 ng/ml at age 20 but declining to an average of 80 ng/ml by age 60. The molecule has a very high affinity for copper and forms the chelate GHK-Cu. The peptide as well as its Cu (II) chelate have anti-inflammatory and tissue remodeling properties. GHK-Cu has been shown to promote skin remodeling, wound healing and regeneration, and has prominent antioxidant and anti-inflammatory effects in in vitro and in vivo studies. In addition, preliminary observations suggest GHK can partially reverse cognitive impairment in aging mice by targeting anti-inflammatory and epigenetic pathways....","authors":"Yan Dou, Amanda Lee, Lida Zhu, John Morton, Warren Ladiges","publishingOrg":null,"publicationYear":2020,"doi":"10.31491/apt.2020.03.014","pubmedId":"35083444","jurisdiction":null,"dateAccessed":"2026-09-08T18:53:38.906Z","editorialNotes":"AI-assisted PubMed corpus expansion; owner authorized 2026-09-08.","sourceType":"peer_reviewed_research","claimSupported":"This source contributes animal_in_vivo evidence concerning The potential of GHK as an anti-aging peptide.","supportNature":"contextualizes","qualification":"Preclinical or mechanistic evidence does not establish human clinical efficacy, safe dose, route, or long-term safety.","verificationStatus":"verified","publicationStatus":"published","addedById":"0bf5b853-ea8b-4aa3-bffe-2af0fdd75150","machineActor":"wpf-five-corpus-expansion-2026-09-08","reviewedById":"0bf5b853-ea8b-4aa3-bffe-2af0fdd75150","canonicalSourceIdentity":"doi:10.31491/apt.2020.03.014","sourceIdentityId":null,"sourceStatus":"active","sourceContentHash":null,"sourceVersion":1,"retrievedAt":"2026-09-08T18:53:38.906Z","retrievalProvider":"NCBI PubMed","retrievalPayloadRef":"wpf:ghk-cu:expansion:2026-09-08","evidenceLane":"animal_in_vivo","extractionPayload":{"limitations":["Preclinical or mechanistic evidence does not establish human clinical efficacy, safe dose, route, or long-term safety."],"studyDesign":"Preclinical experimental study","sourceStrength":{"grade":"B","score":65,"version":"WPF-ESR-1.0","dimensions":{"authority":18,"reporting":10,"directness":15,"replication":"review-sensitive","designAndBias":"publication-type-derived","populationRelevance":"lane-derived"},"provisional":true},"publicationTypes":["Journal Article"]},"provenancePayload":{"doi":"10.31491/apt.2020.03.014","pmid":"35083444","retrievedFrom":"NCBI PubMed"},"validationGates":{"sourceVerified":true,"ownerAuthorized":true,"identityResolved":true,"neutralLanguageVerified":true},"engineState":"promoted_internal","engineRunId":null,"createdAt":"2026-09-08T18:53:38.906Z","updatedAt":"2026-09-08T18:53:38.906Z"},{"id":"14dffba79fb2833425d0952ab672fbba","peptideId":"82d07ce3-167f-4019-b4f2-d802b3cba338","title":"Regenerative and Protective Actions of the GHK-Cu Peptide in the Light of the New Gene Data","sourceUrl":"https://doi.org/10.3390/ijms19071987","evidenceTier":"laboratory","summary":"A review integrates gene-expression findings with tissue-remodeling, inflammatory, antioxidant, and wound-healing hypotheses.","authors":null,"publishingOrg":null,"publicationYear":2018,"doi":"10.3390/ijms19071987","pubmedId":null,"jurisdiction":null,"dateAccessed":"2026-09-08T18:31:47.338Z","editorialNotes":"AI-assisted synthesis; owner-authorized governed publication 2026-09-08.","sourceType":"systematic_review_or_meta_analysis","claimSupported":"Broad transcriptional and tissue-repair hypotheses are described.","supportNature":"contextualizes","qualification":"Heterogeneous models, broad inference, limited independent clinical replication.","verificationStatus":"verified","publicationStatus":"published","addedById":"0bf5b853-ea8b-4aa3-bffe-2af0fdd75150","machineActor":"wpf-reference-corpus-2026-09-08","reviewedById":"0bf5b853-ea8b-4aa3-bffe-2af0fdd75150","canonicalSourceIdentity":"doi:10.3390/ijms19071987","sourceIdentityId":null,"sourceStatus":"active","sourceContentHash":null,"sourceVersion":1,"retrievedAt":"2026-09-08T18:31:47.338Z","retrievalProvider":"PubMed/Crossref verification","retrievalPayloadRef":"wpf:ghk-cu:reference-corpus:2026-09-08","evidenceLane":"systematic_review","extractionPayload":{"finding":"Broad transcriptional and tissue-repair hypotheses are described.","population":"In-vitro, animal, and limited human evidence","sampleSize":null,"limitations":["Heterogeneous models, broad inference, limited independent clinical replication."],"studyDesign":"Narrative review with gene-expression synthesis","sourceStrength":{"note":"Automated baseline based on evidence tier; full-text risk-of-bias review may revise it","grade":"D","score":48,"version":"WPF-ESR-1.0","provisional":true}},"provenancePayload":{"doi":"10.3390/ijms19071987","pmid":null,"reviewBatch":"ghk-cu-reference-corpus-2026-09-08"},"validationGates":{"sourceVerified":true,"ownerAuthorized":true,"identityResolved":true,"neutralLanguageVerified":true},"engineState":"promoted_internal","engineRunId":null,"createdAt":"2026-09-08T18:31:47.338Z","updatedAt":"2026-09-08T18:53:38.906Z"},{"id":"cdfdd2dc311e854e68f1b92ef8609d82","peptideId":"82d07ce3-167f-4019-b4f2-d802b3cba338","title":"GHK Peptide as a Natural Modulator of Multiple Cellular Pathways in Skin Regeneration","sourceUrl":"https://doi.org/10.1155/2015/648108","evidenceTier":"laboratory","summary":"A narrative review synthesizes biochemical, cellular, animal, gene-expression, wound-healing, and limited cosmetic evidence for GHK and GHK-Cu.","authors":null,"publishingOrg":null,"publicationYear":2015,"doi":"10.1155/2015/648108","pubmedId":null,"jurisdiction":null,"dateAccessed":"2026-09-08T18:31:47.338Z","editorialNotes":"AI-assisted synthesis; owner-authorized governed publication 2026-09-08.","sourceType":"systematic_review_or_meta_analysis","claimSupported":"The literature supports multiple plausible regenerative mechanisms, predominantly preclinical.","supportNature":"contextualizes","qualification":"Narrative methods, conflicts, and small or incompletely reported cosmetic studies require caution.","verificationStatus":"verified","publicationStatus":"published","addedById":"0bf5b853-ea8b-4aa3-bffe-2af0fdd75150","machineActor":"wpf-reference-corpus-2026-09-08","reviewedById":"0bf5b853-ea8b-4aa3-bffe-2af0fdd75150","canonicalSourceIdentity":"doi:10.1155/2015/648108","sourceIdentityId":null,"sourceStatus":"active","sourceContentHash":null,"sourceVersion":1,"retrievedAt":"2026-09-08T18:31:47.338Z","retrievalProvider":"PubMed/Crossref verification","retrievalPayloadRef":"wpf:ghk-cu:reference-corpus:2026-09-08","evidenceLane":"systematic_review","extractionPayload":{"finding":"The literature supports multiple plausible regenerative mechanisms, predominantly preclinical.","population":"Laboratory, animal, and limited human skin research","sampleSize":null,"limitations":["Narrative methods, conflicts, and small or incompletely reported cosmetic studies require caution."],"studyDesign":"Narrative literature review","sourceStrength":{"note":"Automated baseline based on evidence tier; full-text risk-of-bias review may revise it","grade":"D","score":48,"version":"WPF-ESR-1.0","provisional":true}},"provenancePayload":{"doi":"10.1155/2015/648108","pmid":null,"reviewBatch":"ghk-cu-reference-corpus-2026-09-08"},"validationGates":{"sourceVerified":true,"ownerAuthorized":true,"identityResolved":true,"neutralLanguageVerified":true},"engineState":"promoted_internal","engineRunId":null,"createdAt":"2026-09-08T18:31:47.338Z","updatedAt":"2026-09-08T18:53:38.906Z"},{"id":"bb2acf44ef7046b57e20f02b84ef1477","peptideId":"82d07ce3-167f-4019-b4f2-d802b3cba338","title":"The human tripeptide GHK-Cu in prevention of oxidative stress and degenerative conditions of aging: implications for cognitive health.","sourceUrl":"https://pubmed.ncbi.nlm.nih.gov/22666519/","evidenceTier":"insufficient","summary":"Oxidative stress, disrupted copper homeostasis, and neuroinflammation due to overproduction of proinflammatory cytokines are considered leading causative factors in development of age-associated neurodegenerative conditions. Recently, a new mechanism of aging-detrimental epigenetic modifications-has emerged. Thus, compounds that possess antioxidant, anti-inflammatory activity as well as compounds capable of restoring copper balance and proper gene functioning may be able to prevent age-associated cognitive decline and ward off many common neurodegenerative conditions. The aim of this paper is to bring attention to a compound with a long history of safe use in wound healing and antiaging...","authors":"Loren Pickart, Jessica Michelle Vasquez-Soltero, Anna Margolina","publishingOrg":null,"publicationYear":2012,"doi":"10.1155/2012/324832","pubmedId":"22666519","jurisdiction":null,"dateAccessed":"2026-09-08T18:53:38.906Z","editorialNotes":"AI-assisted PubMed corpus expansion; owner authorized 2026-09-08.","sourceType":"systematic_review_or_meta_analysis","claimSupported":"This source contributes systematic_review evidence concerning The human tripeptide GHK-Cu in prevention of oxidative stress and degenerative conditions of aging: implications for cognitive health.","supportNature":"contextualizes","qualification":"Narrative synthesis; conclusions depend on source selection and do not substitute for primary clinical evidence.","verificationStatus":"verified","publicationStatus":"published","addedById":"0bf5b853-ea8b-4aa3-bffe-2af0fdd75150","machineActor":"wpf-five-corpus-expansion-2026-09-08","reviewedById":"0bf5b853-ea8b-4aa3-bffe-2af0fdd75150","canonicalSourceIdentity":"doi:10.1155/2012/324832","sourceIdentityId":null,"sourceStatus":"active","sourceContentHash":null,"sourceVersion":1,"retrievedAt":"2026-09-08T18:53:38.906Z","retrievalProvider":"NCBI PubMed","retrievalPayloadRef":"wpf:ghk-cu:expansion:2026-09-08","evidenceLane":"systematic_review","extractionPayload":{"limitations":["Narrative synthesis; conclusions depend on source selection and do not substitute for primary clinical evidence."],"studyDesign":"Narrative review","sourceStrength":{"grade":"B","score":68,"version":"WPF-ESR-1.0","dimensions":{"authority":18,"reporting":10,"directness":15,"replication":"review-sensitive","designAndBias":"publication-type-derived","populationRelevance":"lane-derived"},"provisional":true},"publicationTypes":["Journal Article","Review"]},"provenancePayload":{"doi":"10.1155/2012/324832","pmid":"22666519","retrievedFrom":"NCBI PubMed"},"validationGates":{"sourceVerified":true,"ownerAuthorized":true,"identityResolved":true,"neutralLanguageVerified":true},"engineState":"promoted_internal","engineRunId":null,"createdAt":"2026-09-08T18:53:38.906Z","updatedAt":"2026-09-08T18:53:38.906Z"},{"id":"018c4a95b63fc613ab1decff73f12184","peptideId":"82d07ce3-167f-4019-b4f2-d802b3cba338","title":"The human tri-peptide GHK and tissue remodeling.","sourceUrl":"https://pubmed.ncbi.nlm.nih.gov/18644225/","evidenceTier":"insufficient","summary":"Tissue remodeling follows the initial phase of wound healing and stops inflammatory and scar-forming processes, then restores the normal tissue morphology. The human peptide Gly-(L-His)-(L-Lys) or GHK, has a copper 2+ (Cu(2+)) affinity similar to the copper transport site on albumin and forms GHK-Cu, a complex with Cu(2+). These two molecules activate a plethora of remodeling related processes: (1) chemoattraction of repair cells such as macrophages, mast cells, capillary cells; (2) anti-inflammatory actions (suppression of free radicals, thromboxane formation, release of oxidizing iron, transforming growth factor beta-1, tumor necrosis factor alpha and protein glycation while increasing...","authors":"Loren Pickart","publishingOrg":null,"publicationYear":2008,"doi":"10.1163/156856208784909435","pubmedId":"18644225","jurisdiction":null,"dateAccessed":"2026-09-08T18:53:38.906Z","editorialNotes":"AI-assisted PubMed corpus expansion; owner authorized 2026-09-08.","sourceType":"systematic_review_or_meta_analysis","claimSupported":"This source contributes systematic_review evidence concerning The human tri-peptide GHK and tissue remodeling.","supportNature":"contextualizes","qualification":"Narrative synthesis; conclusions depend on source selection and do not substitute for primary clinical evidence.","verificationStatus":"verified","publicationStatus":"published","addedById":"0bf5b853-ea8b-4aa3-bffe-2af0fdd75150","machineActor":"wpf-five-corpus-expansion-2026-09-08","reviewedById":"0bf5b853-ea8b-4aa3-bffe-2af0fdd75150","canonicalSourceIdentity":"doi:10.1163/156856208784909435","sourceIdentityId":null,"sourceStatus":"active","sourceContentHash":null,"sourceVersion":1,"retrievedAt":"2026-09-08T18:53:38.906Z","retrievalProvider":"NCBI PubMed","retrievalPayloadRef":"wpf:ghk-cu:expansion:2026-09-08","evidenceLane":"systematic_review","extractionPayload":{"limitations":["Narrative synthesis; conclusions depend on source selection and do not substitute for primary clinical evidence."],"studyDesign":"Narrative review","sourceStrength":{"grade":"B","score":68,"version":"WPF-ESR-1.0","dimensions":{"authority":18,"reporting":10,"directness":15,"replication":"review-sensitive","designAndBias":"publication-type-derived","populationRelevance":"lane-derived"},"provisional":true},"publicationTypes":["Journal Article","Review"]},"provenancePayload":{"doi":"10.1163/156856208784909435","pmid":"18644225","retrievedFrom":"NCBI PubMed"},"validationGates":{"sourceVerified":true,"ownerAuthorized":true,"identityResolved":true,"neutralLanguageVerified":true},"engineState":"promoted_internal","engineRunId":null,"createdAt":"2026-09-08T18:53:38.906Z","updatedAt":"2026-09-08T18:53:38.906Z"},{"id":"0b4df9e41db519edac8425100a2e57bc","peptideId":"82d07ce3-167f-4019-b4f2-d802b3cba338","title":"ESI-MS study of the mechanism of glycyl-l-histidyl-l-lysine-Cu(II) complex transport through model membrane of stratum corneum.","sourceUrl":"https://pubmed.ncbi.nlm.nih.gov/19071668/","evidenceTier":"laboratory","summary":"In mammalian organisms copper can be found mainly in the form of complex with specific tripeptide, GHK-Cu (glycyl-l-histidyl-l-lysine-Cu(II)). GHK-Cu is the basic form in which copper is transported in tissues and permeates through cell membranes. The penetration ability of GHK-Cu through the stratum corneum and its role in copper ions transport process is the key issue for its cosmetic and pharmaceutical activity. The permeability phenomenon was studied by use in vitro model system-Flynn diffusion cell with the liposome membrane. The earlier studies on the influence of different ligands on the migration rate of copper ions through model membrane provide evidence for hampering role of...","authors":"Lena Mazurowska, Mirosław Mojski","publishingOrg":null,"publicationYear":2007,"doi":"10.1016/j.talanta.2006.11.034","pubmedId":"19071668","jurisdiction":null,"dateAccessed":"2026-09-08T18:53:38.906Z","editorialNotes":"AI-assisted PubMed corpus expansion; owner authorized 2026-09-08.","sourceType":"peer_reviewed_research","claimSupported":"This source contributes in_vitro evidence concerning ESI-MS study of the mechanism of glycyl-l-histidyl-l-lysine-Cu(II) complex transport through model membrane of stratum corneum.","supportNature":"contextualizes","qualification":"Preclinical or mechanistic evidence does not establish human clinical efficacy, safe dose, route, or long-term safety.","verificationStatus":"verified","publicationStatus":"published","addedById":"0bf5b853-ea8b-4aa3-bffe-2af0fdd75150","machineActor":"wpf-five-corpus-expansion-2026-09-08","reviewedById":"0bf5b853-ea8b-4aa3-bffe-2af0fdd75150","canonicalSourceIdentity":"doi:10.1016/j.talanta.2006.11.034","sourceIdentityId":null,"sourceStatus":"active","sourceContentHash":null,"sourceVersion":1,"retrievedAt":"2026-09-08T18:53:38.906Z","retrievalProvider":"NCBI PubMed","retrievalPayloadRef":"wpf:ghk-cu:expansion:2026-09-08","evidenceLane":"in_vitro","extractionPayload":{"limitations":["Preclinical or mechanistic evidence does not establish human clinical efficacy, safe dose, route, or long-term safety."],"studyDesign":"Preclinical experimental study","sourceStrength":{"grade":"B","score":65,"version":"WPF-ESR-1.0","dimensions":{"authority":18,"reporting":10,"directness":15,"replication":"review-sensitive","designAndBias":"publication-type-derived","populationRelevance":"lane-derived"},"provisional":true},"publicationTypes":["Journal Article"]},"provenancePayload":{"doi":"10.1016/j.talanta.2006.11.034","pmid":"19071668","retrievedFrom":"NCBI PubMed"},"validationGates":{"sourceVerified":true,"ownerAuthorized":true,"identityResolved":true,"neutralLanguageVerified":true},"engineState":"promoted_internal","engineRunId":null,"createdAt":"2026-09-08T18:53:38.906Z","updatedAt":"2026-09-08T18:53:38.906Z"},{"id":"a981414859b54271e8053abfac20e2be","peptideId":"82d07ce3-167f-4019-b4f2-d802b3cba338","title":"Evaluation of the effects of topical tripeptide-copper complex and zinc oxide on open-wound healing in rabbits","sourceUrl":"https://pubmed.ncbi.nlm.nih.gov/?term=%22Evaluation%20of%20the%20effects%20of%20topical%20tripeptide-copper%20complex%22","evidenceTier":"animal","summary":"A controlled rabbit model evaluated topical tripeptide-copper complex and reported wound-healing effects in an animal setting.","authors":null,"publishingOrg":null,"publicationYear":2006,"doi":null,"pubmedId":null,"jurisdiction":null,"dateAccessed":"2026-09-08T18:31:47.338Z","editorialNotes":"AI-assisted synthesis; owner-authorized governed publication 2026-09-08.","sourceType":"peer_reviewed_research","claimSupported":"Topical tripeptide-copper complex altered wound-healing measures in rabbits.","supportNature":"supports","qualification":"Animal and topical findings do not establish efficacy or safety in humans.","verificationStatus":"verified","publicationStatus":"published","addedById":"0bf5b853-ea8b-4aa3-bffe-2af0fdd75150","machineActor":"wpf-reference-corpus-2026-09-08","reviewedById":"0bf5b853-ea8b-4aa3-bffe-2af0fdd75150","canonicalSourceIdentity":"url:https://pubmed.ncbi.nlm.nih.gov/?term=%22Evaluation%20of%20the%20effects%20of%20topical%20tripeptide-copper%20complex%22","sourceIdentityId":null,"sourceStatus":"active","sourceContentHash":null,"sourceVersion":1,"retrievedAt":"2026-09-08T18:31:47.338Z","retrievalProvider":"PubMed/Crossref verification","retrievalPayloadRef":"wpf:ghk-cu:reference-corpus:2026-09-08","evidenceLane":"animal_in_vivo","extractionPayload":{"finding":"Topical tripeptide-copper complex altered wound-healing measures in rabbits.","population":"Rabbits with experimental open wounds","sampleSize":null,"limitations":["Animal and topical findings do not establish efficacy or safety in humans."],"studyDesign":"Controlled animal wound-healing study","sourceStrength":{"note":"Automated baseline based on evidence tier; full-text risk-of-bias review may revise it","grade":"C","score":55,"version":"WPF-ESR-1.0","provisional":true}},"provenancePayload":{"doi":null,"pmid":null,"reviewBatch":"ghk-cu-reference-corpus-2026-09-08"},"validationGates":{"sourceVerified":true,"ownerAuthorized":true,"identityResolved":true,"neutralLanguageVerified":true},"engineState":"promoted_internal","engineRunId":null,"createdAt":"2026-09-08T18:31:47.338Z","updatedAt":"2026-09-08T18:53:38.906Z"},{"id":"791d177debf88ec3419bbf085051a344","peptideId":"82d07ce3-167f-4019-b4f2-d802b3cba338","title":"Expression of glycosaminoglycans and small proteoglycans in wounds: modulation by the tripeptide-copper complex glycyl-L-histidyl-L-lysine-Cu(2+).","sourceUrl":"https://pubmed.ncbi.nlm.nih.gov/11121126/","evidenceTier":"animal","summary":"Glycyl-histidyl-lysine-Cu(2+) is a tripeptide-copper complex previously shown to be an activator of wound healing. We have investigated the effects of glycyl-histidyl-lysine-Cu(2+) on the synthesis of glycosaminoglycans and small proteoglycans in a model of rat experimental wounds and in rat dermal fibroblast cultures. Repeated injections of glycyl-histidyl-lysine-Cu(2+) (2 mg per injection) stimulated the wound tissue production, as appreciated by dry weight and total protein measurements. This stimulation was accompanied by an increased production of type I collagen and glycosaminoglycans (assessed, respectively, by hydroxyproline and uronic acid contents of the chamber)....","authors":"A Siméon, Y Wegrowski, Y Bontemps, F X Maquart","publishingOrg":null,"publicationYear":2000,"doi":"10.1046/j.1523-1747.2000.00166.x","pubmedId":"11121126","jurisdiction":null,"dateAccessed":"2026-09-08T18:53:38.906Z","editorialNotes":"AI-assisted PubMed corpus expansion; owner authorized 2026-09-08.","sourceType":"peer_reviewed_research","claimSupported":"This source contributes animal_in_vivo evidence concerning Expression of glycosaminoglycans and small proteoglycans in wounds: modulation by the tripeptide-copper complex glycyl-L-histidyl-L-lysine-Cu(2+).","supportNature":"contextualizes","qualification":"Preclinical or mechanistic evidence does not establish human clinical efficacy, safe dose, route, or long-term safety.","verificationStatus":"verified","publicationStatus":"published","addedById":"0bf5b853-ea8b-4aa3-bffe-2af0fdd75150","machineActor":"wpf-five-corpus-expansion-2026-09-08","reviewedById":"0bf5b853-ea8b-4aa3-bffe-2af0fdd75150","canonicalSourceIdentity":"doi:10.1046/j.1523-1747.2000.00166.x","sourceIdentityId":null,"sourceStatus":"active","sourceContentHash":null,"sourceVersion":1,"retrievedAt":"2026-09-08T18:53:38.906Z","retrievalProvider":"NCBI PubMed","retrievalPayloadRef":"wpf:ghk-cu:expansion:2026-09-08","evidenceLane":"animal_in_vivo","extractionPayload":{"limitations":["Preclinical or mechanistic evidence does not establish human clinical efficacy, safe dose, route, or long-term safety."],"studyDesign":"Preclinical experimental study","sourceStrength":{"grade":"B","score":65,"version":"WPF-ESR-1.0","dimensions":{"authority":18,"reporting":10,"directness":15,"replication":"review-sensitive","designAndBias":"publication-type-derived","populationRelevance":"lane-derived"},"provisional":true},"publicationTypes":["Journal Article","Research Support, Non-U.S. Gov't"]},"provenancePayload":{"doi":"10.1046/j.1523-1747.2000.00166.x","pmid":"11121126","retrievedFrom":"NCBI PubMed"},"validationGates":{"sourceVerified":true,"ownerAuthorized":true,"identityResolved":true,"neutralLanguageVerified":true},"engineState":"promoted_internal","engineRunId":null,"createdAt":"2026-09-08T18:53:38.906Z","updatedAt":"2026-09-08T18:53:38.906Z"},{"id":"a79b11641d083baf4f5aa5ca27ded5d5","peptideId":"82d07ce3-167f-4019-b4f2-d802b3cba338","title":"The tripeptide-copper complex glycyl-L-histidyl-L-lysine-Cu2+ stimulates matrix metalloproteinase-2 expression by fibroblast cultures.","sourceUrl":"https://pubmed.ncbi.nlm.nih.gov/11045606/","evidenceTier":"animal","summary":"Glycyl-histidyl-lysine-Cu2+ (GHK-Cu) is a tripeptide-copper complex known to be a potent wound healing agent. We previously showed its ability to stimulate in vitro and in vivo the synthesis of extracellular matrix components. The aim of this study was to determine the effects of GHK-Cu on MMP-2 synthesis by dermal fibroblasts in culture. We showed that GHK-Cu increased MMP-2 levels in conditioned media of cultured fibroblasts. This effect was reproduced by copper ions but not by the tripeptide GHK alone. This stimulation was accompanied by an increase of MMP-2 mRNA level. We also showed that GHK-Cu increased the secretion of the tissue inhibitors of metalloproteinases, TIMP-1 and...","authors":"A Siméon, H Emonard, W Hornebeck, F X Maquart","publishingOrg":null,"publicationYear":2000,"doi":"10.1016/s0024-3205(00)00803-1","pubmedId":"11045606","jurisdiction":null,"dateAccessed":"2026-09-08T18:53:38.906Z","editorialNotes":"AI-assisted PubMed corpus expansion; owner authorized 2026-09-08.","sourceType":"peer_reviewed_research","claimSupported":"This source contributes animal_in_vivo evidence concerning The tripeptide-copper complex glycyl-L-histidyl-L-lysine-Cu2+ stimulates matrix metalloproteinase-2 expression by fibroblast cultures.","supportNature":"contextualizes","qualification":"Preclinical or mechanistic evidence does not establish human clinical efficacy, safe dose, route, or long-term safety.","verificationStatus":"verified","publicationStatus":"published","addedById":"0bf5b853-ea8b-4aa3-bffe-2af0fdd75150","machineActor":"wpf-five-corpus-expansion-2026-09-08","reviewedById":"0bf5b853-ea8b-4aa3-bffe-2af0fdd75150","canonicalSourceIdentity":"doi:10.1016/s0024-3205(00)00803-1","sourceIdentityId":null,"sourceStatus":"active","sourceContentHash":null,"sourceVersion":1,"retrievedAt":"2026-09-08T18:53:38.906Z","retrievalProvider":"NCBI PubMed","retrievalPayloadRef":"wpf:ghk-cu:expansion:2026-09-08","evidenceLane":"animal_in_vivo","extractionPayload":{"limitations":["Preclinical or mechanistic evidence does not establish human clinical efficacy, safe dose, route, or long-term safety."],"studyDesign":"Preclinical experimental study","sourceStrength":{"grade":"B","score":65,"version":"WPF-ESR-1.0","dimensions":{"authority":18,"reporting":10,"directness":15,"replication":"review-sensitive","designAndBias":"publication-type-derived","populationRelevance":"lane-derived"},"provisional":true},"publicationTypes":["Journal Article","Research Support, Non-U.S. Gov't"]},"provenancePayload":{"doi":"10.1016/s0024-3205(00)00803-1","pmid":"11045606","retrievedFrom":"NCBI PubMed"},"validationGates":{"sourceVerified":true,"ownerAuthorized":true,"identityResolved":true,"neutralLanguageVerified":true},"engineState":"promoted_internal","engineRunId":null,"createdAt":"2026-09-08T18:53:38.906Z","updatedAt":"2026-09-08T18:53:38.906Z"},{"id":"8977b6e22427fc70f24a3fb47f4e71b2","peptideId":"82d07ce3-167f-4019-b4f2-d802b3cba338","title":"Effects of the tripeptide glycyl-L-histidyl-L-lysine copper complex on osteoblastic cell spreading, attachment and phenotype.","sourceUrl":"https://pubmed.ncbi.nlm.nih.gov/8747089/","evidenceTier":"animal","summary":"We have studied the effects of the complex Glycyl-L-Histidyl-L-Lysine:Cu (GHK:Cu), the GHK sequence present in the alpha 2 (I) chain of human collagen (Coll I), and bone matrix glycoproteins containing either RGD (fibronectin, FN), or RGD and GHK (Coll I), on the spreading, attachment and markers of the osteoblast phenotype in rat calvaria cells (RC), human trabecular osteoblastic cells (HT) and human marrow stromal cells (HM). Coll I (20 micrograms/ml) and FN (20 micrograms/ml) coating enhanced osteoblastic cell spreading, whereas free GHK:Cu and GHK coating (10(-10)-10(-8) M) had no effect. FN and Coll I, as well as GHK:Cu and GHK, increased the attachment of RC and HT cells. The...","authors":"D Godet, P J Marie","publishingOrg":null,"publicationYear":1995,"doi":null,"pubmedId":"8747089","jurisdiction":null,"dateAccessed":"2026-09-08T18:53:38.906Z","editorialNotes":"AI-assisted PubMed corpus expansion; owner authorized 2026-09-08.","sourceType":"peer_reviewed_research","claimSupported":"This source contributes animal_in_vivo evidence concerning Effects of the tripeptide glycyl-L-histidyl-L-lysine copper complex on osteoblastic cell spreading, attachment and phenotype.","supportNature":"contextualizes","qualification":"Preclinical or mechanistic evidence does not establish human clinical efficacy, safe dose, route, or long-term safety.","verificationStatus":"verified","publicationStatus":"published","addedById":"0bf5b853-ea8b-4aa3-bffe-2af0fdd75150","machineActor":"wpf-five-corpus-expansion-2026-09-08","reviewedById":"0bf5b853-ea8b-4aa3-bffe-2af0fdd75150","canonicalSourceIdentity":"pmid:8747089","sourceIdentityId":null,"sourceStatus":"active","sourceContentHash":null,"sourceVersion":1,"retrievedAt":"2026-09-08T18:53:38.906Z","retrievalProvider":"NCBI PubMed","retrievalPayloadRef":"wpf:ghk-cu:expansion:2026-09-08","evidenceLane":"animal_in_vivo","extractionPayload":{"limitations":["Preclinical or mechanistic evidence does not establish human clinical efficacy, safe dose, route, or long-term safety."],"studyDesign":"Preclinical experimental study","sourceStrength":{"grade":"C","score":60,"version":"WPF-ESR-1.0","dimensions":{"authority":18,"reporting":10,"directness":15,"replication":"review-sensitive","designAndBias":"publication-type-derived","populationRelevance":"lane-derived"},"provisional":true},"publicationTypes":["Journal Article"]},"provenancePayload":{"doi":null,"pmid":"8747089","retrievedFrom":"NCBI PubMed"},"validationGates":{"sourceVerified":true,"ownerAuthorized":true,"identityResolved":true,"neutralLanguageVerified":true},"engineState":"promoted_internal","engineRunId":null,"createdAt":"2026-09-08T18:53:38.906Z","updatedAt":"2026-09-08T18:53:38.906Z"},{"id":"a11907a4cb53722057ab85df36013493","peptideId":"82d07ce3-167f-4019-b4f2-d802b3cba338","title":"In vivo stimulation of connective tissue accumulation by the tripeptide-copper complex glycyl-L-histidyl-L-lysine-Cu2+ in rat experimental wounds.","sourceUrl":"https://pubmed.ncbi.nlm.nih.gov/8227353/","evidenceTier":"animal","summary":"The tripeptide-copper complex glycyl-L-histidyl-L-lysine-Cu2+ (GHK-Cu) was first described as a growth factor for differentiated cells. Recent in vitro data showed that it possesses several properties of a potential activator of wound repair. We investigated the effects of GHK-Cu in vivo, using the wound chamber model described previously (Schilling, J.A., W. Joel, and M.T. Shurley, 1959. Surgery [St. Louis]. 46:702-710). Stainless steel wire mesh cylinders were implanted subcutaneously on the back of rats. The animals were divided into groups that received sequential injections into the wound chamber of either saline (control group) or various concentrations of GHK-Cu. At the end of the...","authors":"F X Maquart, G Bellon, B Chaqour, J Wegrowski, L M Patt, R E Trachy, J C Monboisse, F Chastang","publishingOrg":null,"publicationYear":1993,"doi":"10.1172/JCI116842","pubmedId":"8227353","jurisdiction":null,"dateAccessed":"2026-09-08T18:53:38.906Z","editorialNotes":"AI-assisted PubMed corpus expansion; owner authorized 2026-09-08.","sourceType":"peer_reviewed_research","claimSupported":"This source contributes animal_in_vivo evidence concerning In vivo stimulation of connective tissue accumulation by the tripeptide-copper complex glycyl-L-histidyl-L-lysine-Cu2+ in rat experimental wounds.","supportNature":"contextualizes","qualification":"Preclinical or mechanistic evidence does not establish human clinical efficacy, safe dose, route, or long-term safety.","verificationStatus":"verified","publicationStatus":"published","addedById":"0bf5b853-ea8b-4aa3-bffe-2af0fdd75150","machineActor":"wpf-five-corpus-expansion-2026-09-08","reviewedById":"0bf5b853-ea8b-4aa3-bffe-2af0fdd75150","canonicalSourceIdentity":"doi:10.1172/jci116842","sourceIdentityId":null,"sourceStatus":"active","sourceContentHash":null,"sourceVersion":1,"retrievedAt":"2026-09-08T18:53:38.906Z","retrievalProvider":"NCBI PubMed","retrievalPayloadRef":"wpf:ghk-cu:expansion:2026-09-08","evidenceLane":"animal_in_vivo","extractionPayload":{"limitations":["Preclinical or mechanistic evidence does not establish human clinical efficacy, safe dose, route, or long-term safety."],"studyDesign":"Preclinical experimental study","sourceStrength":{"grade":"B","score":65,"version":"WPF-ESR-1.0","dimensions":{"authority":18,"reporting":10,"directness":15,"replication":"review-sensitive","designAndBias":"publication-type-derived","populationRelevance":"lane-derived"},"provisional":true},"publicationTypes":["Journal Article","Research Support, Non-U.S. Gov't"]},"provenancePayload":{"doi":"10.1172/JCI116842","pmid":"8227353","retrievedFrom":"NCBI PubMed"},"validationGates":{"sourceVerified":true,"ownerAuthorized":true,"identityResolved":true,"neutralLanguageVerified":true},"engineState":"promoted_internal","engineRunId":null,"createdAt":"2026-09-08T18:53:38.906Z","updatedAt":"2026-09-08T18:53:38.906Z"},{"id":"564ab51be5206b0b816a4cec80a3b067","peptideId":"82d07ce3-167f-4019-b4f2-d802b3cba338","title":"Stimulation of sulfated glycosaminoglycan synthesis by the tripeptide-copper complex glycyl-L-histidyl-L-lysine-Cu2+.","sourceUrl":"https://pubmed.ncbi.nlm.nih.gov/1522753/","evidenceTier":"laboratory","summary":"Glycyl-L-histidyl-L-lysine-copper (II) complex (GHK-Cu) is a naturally occurring tripeptide with potential healing properties. We studied the effect of GHK-Cu on the synthesis of glycosaminoglycans (GAGs) by normal human fibroblasts in culture. Cells were incubated with 3H glucosamine and 35S sulfate and the radioactivity of isolated GAGs was determined. GHK-Cu induced a dose-dependent increase of the synthesis of total GAGs secreted into the culture medium and those associated with the cell layer. The effect of GHK-Cu was biphasic with a maximal stimulation at 10(-9) to 10(-8) M. At higher concentrations, the rate of synthesis returned progressively to that of control cultures....","authors":"Y Wegrowski, F X Maquart, J P Borel","publishingOrg":null,"publicationYear":1992,"doi":"10.1016/0024-3205(92)90504-i","pubmedId":"1522753","jurisdiction":null,"dateAccessed":"2026-09-08T18:53:38.906Z","editorialNotes":"AI-assisted PubMed corpus expansion; owner authorized 2026-09-08.","sourceType":"peer_reviewed_research","claimSupported":"This source contributes in_vitro evidence concerning Stimulation of sulfated glycosaminoglycan synthesis by the tripeptide-copper complex glycyl-L-histidyl-L-lysine-Cu2+.","supportNature":"contextualizes","qualification":"Preclinical or mechanistic evidence does not establish human clinical efficacy, safe dose, route, or long-term safety.","verificationStatus":"verified","publicationStatus":"published","addedById":"0bf5b853-ea8b-4aa3-bffe-2af0fdd75150","machineActor":"wpf-five-corpus-expansion-2026-09-08","reviewedById":"0bf5b853-ea8b-4aa3-bffe-2af0fdd75150","canonicalSourceIdentity":"doi:10.1016/0024-3205(92)90504-i","sourceIdentityId":null,"sourceStatus":"active","sourceContentHash":null,"sourceVersion":1,"retrievedAt":"2026-09-08T18:53:38.906Z","retrievalProvider":"NCBI PubMed","retrievalPayloadRef":"wpf:ghk-cu:expansion:2026-09-08","evidenceLane":"in_vitro","extractionPayload":{"limitations":["Preclinical or mechanistic evidence does not establish human clinical efficacy, safe dose, route, or long-term safety."],"studyDesign":"Preclinical experimental study","sourceStrength":{"grade":"B","score":65,"version":"WPF-ESR-1.0","dimensions":{"authority":18,"reporting":10,"directness":15,"replication":"review-sensitive","designAndBias":"publication-type-derived","populationRelevance":"lane-derived"},"provisional":true},"publicationTypes":["Journal Article","Research Support, Non-U.S. Gov't"]},"provenancePayload":{"doi":"10.1016/0024-3205(92)90504-i","pmid":"1522753","retrievedFrom":"NCBI PubMed"},"validationGates":{"sourceVerified":true,"ownerAuthorized":true,"identityResolved":true,"neutralLanguageVerified":true},"engineState":"promoted_internal","engineRunId":null,"createdAt":"2026-09-08T18:53:38.906Z","updatedAt":"2026-09-08T18:53:38.906Z"},{"id":"6f128665d6d60f44cc4ff985650df5c5","peptideId":"82d07ce3-167f-4019-b4f2-d802b3cba338","title":"Stimulation of collagen synthesis in fibroblast cultures by the tripeptide-copper complex glycyl-L-histidyl-L-lysine-Cu2+.","sourceUrl":"https://pubmed.ncbi.nlm.nih.gov/3169264/","evidenceTier":"laboratory","summary":"Glycyl-L-histidyl-L-lysine (GHK) is a tripeptide with affinity for copper(II) ions and was isolated from human plasma. This peptide appears to play a physiological role in wound healing. We report the stimulating effect of GHK-Cu on collagen synthesis by fibroblasts. The stimulation began between 10(-12) and 10(-11) M, maximized at 10(-9) M, and was independent of any change in cell number. The presence of a GHK triplet in the alpha 2(I) chain of type I collagen suggests that the tripeptide might be liberated by proteases at the site of a wound and exert in situ healing effects.","authors":"F X Maquart, L Pickart, M Laurent, P Gillery, J C Monboisse, J P Borel","publishingOrg":null,"publicationYear":1988,"doi":"10.1016/0014-5793(88)80509-x","pubmedId":"3169264","jurisdiction":null,"dateAccessed":"2026-09-08T18:53:38.906Z","editorialNotes":"AI-assisted PubMed corpus expansion; owner authorized 2026-09-08.","sourceType":"peer_reviewed_research","claimSupported":"This source contributes in_vitro evidence concerning Stimulation of collagen synthesis in fibroblast cultures by the tripeptide-copper complex glycyl-L-histidyl-L-lysine-Cu2+.","supportNature":"contextualizes","qualification":"Preclinical or mechanistic evidence does not establish human clinical efficacy, safe dose, route, or long-term safety.","verificationStatus":"verified","publicationStatus":"published","addedById":"0bf5b853-ea8b-4aa3-bffe-2af0fdd75150","machineActor":"wpf-five-corpus-expansion-2026-09-08","reviewedById":"0bf5b853-ea8b-4aa3-bffe-2af0fdd75150","canonicalSourceIdentity":"doi:10.1016/0014-5793(88)80509-x","sourceIdentityId":null,"sourceStatus":"active","sourceContentHash":null,"sourceVersion":1,"retrievedAt":"2026-09-08T18:53:38.906Z","retrievalProvider":"NCBI PubMed","retrievalPayloadRef":"wpf:ghk-cu:expansion:2026-09-08","evidenceLane":"in_vitro","extractionPayload":{"limitations":["Preclinical or mechanistic evidence does not establish human clinical efficacy, safe dose, route, or long-term safety."],"studyDesign":"Preclinical experimental 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