InsufficientPreprint
This study investigates GHK-Cu — a copper-based amino acid complex — as an interfacial modifier inserted between the perovskite layer and the Spiro-OMeTAD hole-transport layer (HTL) in perovskite solar cells (PSCs). The researchers found that GHK-Cu's molecular flexibility and polarity-responsive coordination chemistry allowed it to expose multiple functional groups (─C=O, ─COOH, and ─NH₂) that interact with undercoordinated ionic defects via coordination bonds and hydrogen bonding. These interactions drove GHK-Cu to self-assemble into a mesoporous architecture at the interface, which then reorganized Spiro-OMeTAD into a hybrid mesoporous@Spiro-OMeTAD HTL. The authors report that this structure creates continuous hole-transport channels, reduces thermomechanical stress, and suppresses ion migration. Devices incorporating this interlayer reportedly achieved a power conversion efficiency (PCE) of 26.72%, with a certified PCE of 26.34%, and retained 95% of initial efficiency after 1,600 hours of maximum power point tracking at 85°C. Limitations include the preprint status of the work, meaning it has not yet undergone formal peer review, and the results reflect a specific device architecture that may not generalize broadly.
Unknown journal · Jun 2026DOI ↗ Animal onlyPreprint
This preclinical study investigated whether the endogenous copper-binding peptide GHK-Cu (glycyl-L-histidyl-L-lysine–copper complex) could mitigate age-related cognitive decline in middle-aged to old C57BL/6J mice (20–21 months). Two delivery routes were compared: short-term intraperitoneal (IP) administration over 5 days and longer-term intranasal (IN) administration over 8 weeks. Hippocampal-dependent spatial learning was assessed via an escape latency task; molecular changes were examined through hippocampal immunohistochemistry and bulk RNA sequencing, with differential gene expression analyzed using DESeq2 and gene set enrichment analysis (GSEA). Both delivery routes were associated with improved escape latency performance in treated mice of both sexes compared to controls, suggesting behavioral rescue of age-related learning deficits. However, the two routes produced divergent hippocampal transcriptomic profiles, implying that delivery method and exposure duration engage distinct molecular aging programs. Key limitations include the exclusive use of a mouse model, the absence of human data, variability in statistical power across outcome measures, and preprint status meaning the findings have not yet undergone formal peer review. The study does not establish causality in humans and is hypothesis-generating for future translational research.
Unknown journal · May 2026DOI ↗ Animal only
This study investigated whether GHK-Cu (the tripeptide Glycine-Histidine-Lysine complexed with copper, naturally found in human plasma and urine) could delay aging using the roundworm Caenorhabditis elegans as a model organism. The researchers measured lifespan, stress resistance (oxidative and thermal), physical function (motility, pharyngeal pumping, defecation rhythm), and markers of cellular aging such as lipofuscin and lipid accumulation. They also examined mitochondrial health and key longevity signaling pathways. The study found that GHK-Cu extended worm lifespan, improved multiple age-related functional measures, and reduced aging biomarkers. At the mechanistic level, GHK-Cu appeared to preserve mitochondrial function—maintaining membrane potential, reducing age-related mitochondrial fragmentation, promoting mitochondrial fusion (via regulation of drp-1 and fzo-1), and increasing ATP production. Additionally, GHK-Cu activated the DAF-16 and SKN-1 longevity pathways and upregulated downstream target genes including sod-3, gst-4, gcs-1, lys-7, and lys-8. A key limitation is that all experiments were conducted in C. elegans; whether these findings translate to mammals or humans remains unknown.
Biogerontology · May 2026DOI ↗ InsufficientPreprint
This study analyzed a large, publicly available independent testing dataset of 6,441 samples spanning fourteen peptide compounds sold through largely unregulated gray market channels directly to consumers. Compounds examined included BPC-157, semaglutide, tirzepatide, PT-141, TB-500, thymosin beta-4, and others marketed for purposes such as injury recovery, muscle growth, fat loss, and athletic performance. Researchers applied two quality acceptance frameworks — one approximating standards for 503A compounded medications and a stricter model reflecting FDA-approved drug production standards — to assess purity, measured abundance, and endotoxin burden. The study found that between 41.6% and 71.1% of samples failed to meet basic quality criteria depending on the framework applied, and measurable endotoxin contamination was detected in 15% of samples. Gray market peptides were consistently cheaper than FDA-approved alternatives, though cost differentials varied widely (e.g., 72.8% higher for tirzepatide vs. 3,850% higher for PT-141 when comparing FDA-approved options). The authors concluded that consumer-directed third-party testing improves transparency but captures only a fraction of the full safety profile relevant to patients self-administering injectable compounds. Key limitations include reliance on a secondary dataset not collected under controlled research conditions and the inability to assess many other safety dimensions beyond purity and endotoxin levels.
Unknown journal · Apr 2026DOI ↗ Preclinical
This study developed a multifunctional injectable hydrogel called HCG@CDs designed to treat radiation-induced skin injury (RISI), a common complication of cancer radiotherapy. The hydrogel was constructed by cross-linking carboxymethyl chitosan (CMCS) with oxidized hyaluronic acid (OHA) conjugated to a Glycyl-L-Histidyl-L-Lysine-Copper(II) complex (GHK-Cu²⁺) via dynamic Schiff-base bonds, with carbon dots (CDs) possessing superoxide dismutase (SOD)-like activity dispersed throughout the network. The system was designed for sequential, pH-responsive drug release: CDs are rapidly released in the acidic wound environment to scavenge reactive oxygen species (ROS) and reduce early oxidative stress, while GHK-Cu²⁺ is released more gradually to promote inflammation modulation, cell migration, proliferation, and collagen deposition. Both in vitro cell-based assays and in vivo animal model experiments were conducted, with results reportedly showing reduced oxidative damage, attenuated inflammatory responses, and accelerated wound healing. Limitations include reliance on preclinical models (cell culture and animal studies), with no human clinical data presented. The translational relevance to human RISI treatment remains to be established through further clinical investigation.
Bioactive materials · Apr 2026DOI ↗ In vitro
This computational study introduces the concept of "carbonless" biomolecular design, in which all carbon atoms in amino acids and peptides are systematically replaced by boron and nitrogen atoms under an isoelectronicity constraint. Using glycine, histidine, lysine, and the copper-binding tripeptide Gly-His-Lys (GHK) as model systems, the researchers applied density functional theory (DFT) calculations with aqueous solvation modeling and conformer sampling to identify the most stable carbonless analogues (cGly, cHis, cLys, and cGHK) among all possible boron-nitrogen constitutional isomers. The study predicted that cGHK displays a broader conformational landscape than native GHK under physiological aqueous conditions, suggesting enhanced structural flexibility. Copper(II) binding was modeled using an experimentally informed coordination motif, and thermodynamic calculations indicated that cGHK binds Cu(II) more favorably than GHK by approximately 6.24 kcal/mol. The work is entirely theoretical; no synthesis, cell-based, animal, or human experiments were conducted. Limitations include the absence of experimental validation of the proposed carbonless structures, reliance on computational approximations for solvation and conformational sampling, and uncertainty about whether these novel BN-substituted molecules could be synthesized or would exhibit biological stability.
Physical chemistry chemical physics : PCCP · Apr 2026DOI ↗ Animal only
This study investigated the anti-inflammatory and antioxidant properties of the bioactive tripeptide complex GHK-Cu (Glycyl-L-histidyl-L-lysine-Cu²⁺) using zebrafish larvae as an in vivo model. Researchers induced acute inflammation in larvae using either copper sulfate (CuSO₄) or lipopolysaccharide (LPS) and then assessed the effects of GHK-Cu treatment. According to the study, GHK-Cu notably reduced the migration of neutrophils and macrophages to sites of inflammation. It also suppressed the gene expression of pro-inflammatory cytokines (TNF-α, IL-1β, and IL-6) while upregulating the anti-inflammatory cytokine IL-10. The compound was further reported to reduce markers of oxidative stress, including nitric oxide (NO) and reactive oxygen species (ROS), and to improve superoxide dismutase (SOD) activity. Pathway analysis suggested that GHK-Cu's effects may be mediated in part through downregulation of the JAK1 signaling pathway. The authors propose that these findings provide a theoretical basis for the use of GHK-Cu as a functional cosmetic ingredient. Key limitations include the use of a non-mammalian animal model and the absence of human or cell-culture mechanistic data, meaning clinical translation remains unestablished.
European journal of pharmacology · Apr 2026DOI ↗ Animal onlyPreprint
This mouse study investigated whether the endogenous copper-binding peptide GHK-Cu could improve age-related cognitive decline, and whether outcomes differed based on how the compound was delivered. Aged C57BL/6J mice (20–21 months old) received GHK-Cu either intraperitoneally (IP) for 5 days or intranasally (IN) for 8 weeks. Researchers assessed hippocampal-dependent spatial learning, along with hippocampal tissue markers and bulk RNA sequencing. Both delivery routes were associated with improvements in escape learning, though IN administration showed broader and more sustained benefits across both sexes, while IP dosing produced a more limited effect, primarily in males. Immunohistochemistry revealed route-dependent changes in markers of synaptic density (synaptophysin), neuroinflammation (GFAP, MCP-1, TGF-β), and cellular senescence (p21). Transcriptomic analysis showed striking divergence: IN treatment was associated with suppression of oxidative phosphorylation and MYC target pathways, while IP treatment activated stress-response, DNA repair, and mitochondrial metabolic pathways. The authors conclude that GHK-Cu can improve cognitive outcomes through mechanistically distinct biological programs depending on the route and duration of administration. Key limitations include use of a single rodent strain, lack of human data, and preprint status (not yet peer-reviewed).
Unknown journal · Apr 2026DOI ↗ In vitro
This study investigated the catalytic properties of GHK-Cu (a copper-bound tripeptide composed of glycine, histidine, and lysine) as a mimic of the enzyme laccase, which is naturally used in the detection and degradation of phenolic compounds. Researchers characterized GHK-Cu's enzyme-like kinetics, finding a maximum reaction velocity (Vmax) of 1.735 × 10⁻⁴ mM·s⁻¹ and a Michaelis constant (Km) of 0.061 mM, suggesting strong substrate affinity and catalytic efficiency compared to natural laccase. Building on this, the team developed colorimetric assays to detect two phenolic compounds—epinephrine (EP) and 2-aminophenol (2-AP)—across defined concentration ranges in ultrapure water and seawater. Additionally, a portable cotton-based sensor paired with a smartphone platform was constructed to enable field-ready detection of 2-AP in seawater. The study is conducted entirely in vitro and focuses on analytical chemistry applications rather than biological or therapeutic effects of GHK-Cu. Key limitations include the absence of any cell-based, animal, or human testing; findings are restricted to a controlled laboratory sensing context. The work proposes GHK-Cu's copper-coordination structure as a template for designing novel synthetic laccase mimetics.
Biosensors · Apr 2026DOI ↗ Review
This narrative review examines the pharmacological mechanisms, safety profiles, and regulatory status of twelve peptides commonly marketed in sports medicine contexts, spanning both FDA-approved compounds (e.g., tesamorelin/Egrifta) and unapproved "gray market" substances (e.g., BPC-157, CJC-1295, TB-500, ipamorelin, and others). The authors note that while many unapproved peptides show promising tissue repair and metabolic effects in animal models, rigorous human safety and efficacy data are largely absent. The review highlights a growing direct-to-consumer gray market operating outside regulatory oversight and discusses the potential for serious patient harm. Notably, the authors address the placebo effect as a possible mediator of perceived peptide efficacy and examine how social media may amplify this effect. A clinician-oriented framework is proposed to guide evidence-based patient discussions about peptide use for musculoskeletal healing and athletic performance, including consideration of alternative treatments. Key limitations include the narrative (non-systematic) review methodology and the inherently limited and heterogeneous evidence base for most compounds discussed, particularly in human populations.
Sports medicine (Auckland, N.Z.) · Apr 2026DOI ↗ ReviewPreprint
This narrative review examines the pharmacological mechanisms, safety profiles, and regulatory status of twelve peptides commonly encountered in sports medicine and athletic performance contexts, including both approved agents (e.g., tesamorelin/Egrifta, sermorelin) and unapproved "gray market" compounds (e.g., BPC-157, CJC-1295, TB-500, ipamorelin, AOD-9604, FS-344, GHK-Cu, MOTS-C, SS-31, and thymosin beta-4). The authors note that while many unapproved peptides show promising tissue repair and metabolic outcomes in animal models, rigorous human safety and efficacy data remain scarce. The review highlights the emergence of a direct-to-consumer gray market operating outside regulatory oversight and the potential for serious patient harm. It further discusses the placebo effect as a potential mediator of perceived peptide efficacy, and how social media may amplify this effect. The authors provide a clinical framework to guide patient-provider discussions and promote evidence-based practice for musculoskeletal healing. Key limitations include the narrative (non-systematic) review design, reliance on preclinical literature for most unapproved compounds, and the absence of head-to-head human trials for the majority of agents discussed.
Unknown journal · Apr 2026DOI ↗ Review
This comprehensive narrative review examines nine therapeutic peptides with proposed applications in healthy aging and age-related conditions: tirzepatide (metabolic dysfunction), epitalon (telomere biology), GHK-Cu (dermal regeneration), BPC-157 and TB-500 (tissue repair), Semax (neuroprotection), CJC-1295 and ipamorelin (growth hormone modulation), and bremelanotide (sexual function). The authors searched PubMed, Scopus, and regulatory databases through January 2026, selecting 20 primary sources based on relevance and methodological quality. The review found that FDA-approved agents such as tirzepatide and bremelanotide have robust safety and efficacy data from large-scale trials, while investigational peptides such as epitalon, BPC-157, and TB-500 show promising signals primarily from preclinical and limited clinical studies. The authors highlight significant knowledge gaps, including the absence of long-term safety data for non-approved peptides, undefined optimal dosing regimens, unknown combination therapy effects, and lack of validated biomarkers for monitoring efficacy. The authors conclude that while therapeutic peptides offer mechanistically diverse approaches to aging hallmarks, investigational agents require rigorous clinical trial validation before clinical adoption. As a narrative review, findings are subject to selection bias and do not represent a quantitative synthesis of evidence.
Frontiers in aging · Apr 2026DOI ↗ Review
This narrative review examines the potential role of therapeutic peptides in orthopaedic care, synthesizing preclinical and mechanistic literature across several peptide classes. The authors categorize peptides by their primary proposed function: wound-healing agents (BPC-157, TB-500, GHK-Cu), growth hormone secretagogues (ipamorelin, CJC-1295, tesamorelin, sermorelin, AOD-9604), recovery-enhancing peptides (epithalon, delta sleep-inducing peptide, pinealon), and neuroactive peptides (selank, semax, dihexa). The review describes how these compounds are theorized to interact with signaling pathways—including PI3K/Akt, mTOR, MAPK, TGF-β, and AMPK—to promote tissue regeneration, resolve inflammation, and support neuromuscular recovery. The authors acknowledge that, while preclinical evidence is promising, robust human clinical trial data are largely absent, representing a significant gap in the literature. Limitations include the review's reliance on animal and in vitro studies, the absence of a systematic search methodology, and the lack of direct clinical evidence supporting efficacy or safety in human orthopaedic populations. The authors call for future controlled trials to validate these mechanistic findings in clinical settings.
Journal of the American Academy of Orthopaedic Surgeons. Global research & reviews · Jan 2026DOI ↗ Review
This narrative review, aimed at orthopaedic and sports medicine physicians, synthesizes the existing biochemical and clinical literature on six commonly marketed injectable therapeutic peptides: BPC-157, TB-4, TB-500, CJC-1295 + ipamorelin, tesamorelin, and GHK-Cu. The authors conducted a PubMed literature search and evaluated evidence across preclinical and clinical settings. Key findings attributed to the reviewed studies include: BPC-157 showed potential in tendon and muscle repair in preclinical models, with one human case series reporting pain reduction after intra-articular knee injection, though that study had significant methodological limitations and no control group. TB-4 and TB-500 demonstrated angiogenesis and tissue repair effects in animal models, but no human orthopaedic data were identified, and both are banned in sport. CJC-1295 combined with ipamorelin improved muscle tension in a murine glucocorticoid-induced muscle loss model only. Tesamorelin holds FDA approval for HIV-associated lipodystrophy but lacks orthopaedic evidence. GHK-Cu showed wound healing and anti-inflammatory properties preclinically, with no clinical musculoskeletal data. The authors conclude that indications, safety profiles, and dosing for all these peptides remain undefined for orthopaedic use, and robust human trials are needed before clinical recommendations can be made.
The American journal of sports medicine · Jan 2026DOI ↗ In vitro
This review/research paper examines two naturally occurring peptides — carnosine (β-alanyl-L-histidine) and GHK (glycyl-L-histidyl-L-lysine) — and explores strategies to improve their stability and bioavailability through glycoconjugation. A key challenge addressed is the rapid degradation of carnosine by the enzyme carnosinase and the inherent low stability of GHK. The authors report that conjugating these peptides to either trehalose (a disaccharide) or hyaluronan (a polysaccharide) inhibits carnosinase activity and increases tripeptide stability, while also protecting the saccharide components from degradation. The study further investigates copper-binding properties of these glycoconjugates, finding that the saccharide components potentiate the Cu,Zn-superoxide dismutase-like (antioxidant) activity of the resulting copper(II) complexes. The glycoconjugates are reported to act as copper ionophores in cell culture, increasing intracellular copper levels and stimulating copper-driven signaling pathways, leading to enhanced expression of trophic and angiogenic proteins including BDNF, BMP-2, and VEGF. Copper chaperones CCS and Atox-1 are implicated as transcription factors in these pathways. Limitations include reliance on in vitro cell culture models and biochemical assays, with no human clinical data presented.
Antioxidants (Basel, Switzerland) · Dec 2025DOI ↗ ReviewPreprint
This review paper examines the pharmacological mechanisms, safety profiles, and regulatory status of both approved and unapproved peptide therapies relevant to sports medicine, musculoskeletal injury recovery, and athletic performance enhancement. The compounds reviewed span a wide spectrum — from FDA-approved agents such as tesamorelin and sermorelin, to gray-market compounds including BPC-157, TB-500, CJC-1295, Ipamorelin, AOD-9604, FS-344, GHK-Cu, MOTS-C, and SS-31. The authors note that while many unapproved peptides show promising results in preclinical and animal models — including favorable tissue repair and metabolic effects — rigorous human safety and efficacy data remain scarce. The review highlights a growing direct-to-consumer gray market operating outside regulatory oversight and discusses how social media may amplify perceived benefits through placebo-related mechanisms. The paper also offers a clinical framework to guide patient conversations and support evidence-based decision-making. Key limitations include the inherent constraints of a narrative review design, reliance on heterogeneous preclinical data for unapproved compounds, and the absence of controlled human trials for most of the highlighted peptides.
Unknown journal · Dec 2025DOI ↗ Animal only
This study introduced a Golgi-targeted copper delivery system (LNP-ATOX1/GHK-Cu@PCL-GelMA) designed to enhance the activity of copper-dependent proteins—particularly lysyl oxidase (LOX)—to promote fascia regeneration. The system combined GHK-Cu (a copper-peptide complex) as a sustained-release copper source with lipid nanoparticles (LNPs) delivering mRNA encoding ATOX1, a copper chaperone that shuttles copper into the Golgi apparatus via ATP7A/B transporters. In vitro experiments showed the system significantly increased Golgi copper accumulation, raised LOX activity to approximately 1.78 times that of controls, and enhanced angiogenic capacity. The researchers also reported that ATOX1 upregulation promoted copper-dependent translocation of ATP7A and Rac1 to the plasma membrane, potentially supporting neovascularization. In a rabbit fascia defect animal model, the strategy improved collagen alignment, neovascularization, and extracellular matrix reconstruction. Limitations include the absence of human or large-animal data, reliance on a single animal model, and the translational gap between rabbit fascia repair and human clinical outcomes. No human trials were conducted.
Journal of controlled release : official journal of the Controlled Release Society · Dec 2025DOI ↗ Review
This comprehensive review synthesizes research published between 2016 and 2025 on the role of tripeptides in wound healing and skin regeneration. The authors examine how these short, three-amino-acid peptides regulate critical repair processes including cell migration, proliferation, and differentiation, as well as inflammation modulation, angiogenesis promotion, and extracellular matrix (ECM) remodeling. The review highlights several specific tripeptides: GHK-based formulations (including nanoparticle conjugates, hydrogels, and clinical derivatives TriHex and TriHex 2.0) were found in cited studies to enhance fibroblast migration, collagen and elastin synthesis, ECM remodeling, and wound closure with added antimicrobial activity. KdPT was reported to mitigate hyperglycemia-induced oxidative stress and restore keratinocyte function, while KPV-loaded hydrogels reduced inflammation and combated MRSA infections. Lipotripeptides (DICAMs) were noted to inhibit and disrupt bacterial biofilms, and GPE was associated with neuroprotection via ERK and PI3K/Akt signaling. The review also addresses physicochemical comparisons with larger peptides, biomaterial scaffold integration, and emerging applications in cancer and cosmetics. As a narrative review, it does not generate new experimental data. Key limitations include inherent selection bias and the predominance of preclinical evidence in the underlying literature. The authors call for further research into stability, bioavailability, and delivery optimization.
International journal of medical sciences · Oct 2025DOI ↗ Preclinical
This study developed a novel injectable soft tissue filler by loading the GHK-Cu tripeptide (glycyl-L-histidyl-L-lysine copper complex) onto hydroxyapatite microspheres (HAPs), which were then combined with carboxymethyl cellulose, glycerol, and water to form a gel formulation called GHK-Cu@CMHA. The researchers report this is the first combination of HAPs and GHK-Cu designed to address implant-induced inflammation. The formulation demonstrated sustained GHK-Cu release over 7 days in laboratory testing, along with good flowability and injectability. Using a lipopolysaccharide (LPS)-induced inflammation model tested both in cell culture (in vitro) and in animals (in vivo), the study found that GHK-Cu@CMHA reduced levels of inflammatory cytokines and reactive oxygen species (ROS), while increasing superoxide dismutase (SOD) activity, suggesting antioxidant effects. Histological staining (H&E and Masson) indicated collagen deposition at treatment sites. Key limitations include the absence of human data, reliance on an LPS-induced inflammation model that may not fully replicate clinical filler complications, and no long-term safety or efficacy follow-up. These findings are preliminary and require further clinical validation before any conclusions about human benefit can be drawn.
Colloids and surfaces. B, Biointerfaces · Jul 2025DOI ↗ Animal only
This study investigated the therapeutic potential of GHK-Cu (glycyl-l-histidyl-l-lysine-copper) in ulcerative colitis (UC) using a dextran sulfate sodium (DSS)-induced mouse model and complementary cell-based experiments. Researchers administered GHK-Cu to BALB/c mice with DSS-induced colitis and assessed disease activity, colon histology, goblet cell counts, tight junction proteins (ZO-1, Occludin), inflammatory cytokines (TNF-α, IL-6, IL-1β), and key signaling proteins (SIRT1, STAT3, p-STAT3, RORγt). Network pharmacology and molecular docking were used to predict SIRT1 as a core target. A co-culture model of mouse colonic epithelial cells (MCECs) and peritoneal macrophages confirmed GHK-Cu's role in mucosal healing. STAT3 silencing via siRNA revealed that STAT3 is required for GHK-Cu's promotion of epithelial healing and tight junction protein upregulation, but not for its anti-inflammatory effects, suggesting additional pathways are involved. The study found that GHK-Cu reduced disease severity, suppressed inflammation, enhanced mucosal repair via the SIRT1/STAT3 pathway, and decreased RORγt expression, suggesting reduced Th17 cell activity. Limitations include exclusive use of animal and in vitro models with no human data.
Frontiers in pharmacology · Jul 2025DOI ↗