GHK-Cu (Copper Peptide)

Studies(5) have suggested that the peptide exhibits potential in gene expression and may reset elements of the genome. By this potential mechanism, GHK-Cu peptide may restore impaired cells, including cancer cells and COPD cells. GHK-Cu peptide has been investigated for its potential across a variety of functions(1) including that it may tighten and reverse the thinning of aged skin structure, supporting the extracellular matrix, which may restore the skin barrier and moderate texture, hyperpigmentation, and lesions, it may support tissue repair and mitigate inflammation, it may stimulate increased hair follicle size, it may exert antioxidant properties, and finally, it may exhibit gene restructuring potential.

Specifications

• Molecular Formula: C14H23CuN6O4
• Molecular Weight: 340.38 g/mol
• Other Known Titles: glycyl-L-histidyl-L-lysine-copper 2+

This study from the 1980s(6) suggested the biological potential of the natural peptide in tissue repair. The GHK peptide can harbor copper (II) ions due to potential copper affinity and thus may stimulate collagen synthesis and increase total protein and DNA accumulation at the injury site. Dermal wound rats were used for this study. At the time of injury, GHK peptide release was induced. 'Emergency response molecules' were released from the matrix at the injury site. Once released, GHK appeared to bind with Cu ions found in the blood and then stimulate the synthesis of the protein decorin. The protein decorin is responsible for collagen synthesis and regulation of wound healing and the anti-tumor defense mechanism. Additional studies in the 2000s(7) suggested that the GHK-Cu peptide harbors the potential not only to stimulate collagen synthesis but also to stimulate the production of tissue inhibitors, TIMP-1 and TIMP-2.

In this study,(8) the primary objective was to understand the action of the GHK-Cu peptide complex when applied to open wounds compared to zinc oxide. 18 New Zealand white rabbits were used for this study, divided into three groups: one group presented with GHK-Cu, the second group with zinc oxide, and the third group with placebo. Wounds were induced in each rabbit and the rabbits were presented with the respective compounds for 21 consecutive days. After 21 days, researchers suggested that the group administered the GHK-Cu peptide complex appeared to exhibit greater healing compared to the group administered zinc oxide or placebo.

In this study,(9) the primary objective was to understand the action of the GHK-Cu peptide complex compared to helium-neon laser. Laser applications were measured at 1 J cm2 and 3 J cm2. 24 New Zealand white rabbits were used for this study, divided into three groups and presented with the respective concentrations of the GHK-Cu peptide complex and helium-neon laser application. Experimental wounds were created in all rabbits and all rabbits were studied for 28 consecutive days with the respective compounds. After the study, researchers suggested that the rabbits studied with GHK-Cu peptide and a higher concentration of laser application appeared more responsive to wound healing than the other group. Rabbits presented with GHK-Cu peptide exhibited an apparent decrease in neutrophil counts and an increase in neovascularization.

In this 1983 study,(1) the actions of the GHK-Cu complex and ascorbic acid (Vitamin C) mixture on sarcoma (tumor) cell growth were observed. 180 mice with cancerous growths were exposed to this mixture. Researchers suggested that the mixture had the potential to induce a decrease in cancerous cell growth in subject mice. subsequently, researchers reported that the GHK-Cu peptide complex exhibited some potential to increase caspase expression and associated genes, as well as gene expression associated with DNA repair. Specifically, this peptide appeared to suppress the growth of two types of cancer cells in experimental settings: SH-SY5Y neuroblastoma cells, which are a model for studying nerve cell behavior and pathology, and U937 histiocytic lymphoma cells, which are used to study the immune system's response to cancer. Furthermore, the peptide may have reactivated the apoptosis pathway, a type of programmed cell death crucial for eliminating defective cells, as evidenced by activity in caspases 3 and 7, which are enzymes playing a key role in apoptosis. Conversely, in a study of non-cancerous cells, GHK appeared to promote the growth of NIH-3T3 fibroblasts, which are healthy cells often used as a standard model for examining cell division and growth.

This clinical study(10) was conducted on diabetic subjects with neuropathic ulcers. All subjects were enrolled in a standard wound care protocol, where only subjects with sharp ulcer wounds or debridement entered this randomized, placebo-controlled clinical trial. The study was conducted using GHK-Cu peptide complex gel. All subjects were divided into different groups, where one group was presented with the peptide gel, while others were given standard care with a placebo application. After the study, researchers suggested that subjects receiving the gel exhibited apparently elevated healing to 98%+. The gel complex appeared to have the potential to induce 98.5% closure of plantar ulcers, while the control only purportedly induced 60.8% ulcer healing.

In this study,(1) GHK-Cu was administered to mice to measure pain mitigation. Mice were placed on a moderately hot plate. Due to the heat and pain, it would generally take longer for mice to lick their paws; however, following peptide administration, the time taken to lick their paws was reduced compared to control settings. Researchers suggested that the mice felt 'comfortable' and their pain was alleviated faster with the presence of GHK-Cu.

In this study,(11) male rats were placed in a maze, which was intended to induce anxiety and cause behavioral changes. If anxious, rats were observed to restrict arm movement, keeping "arms closed"; whereas "open arm" behavior was shown in rats with reduced anxiety levels. As part of the study, once the peptide was administered, the time rats spent in an "open arm" state in the maze was monitored. After the study, researchers reported that the peptide exhibited some potential to increase "open arm" states in subjects.

In a further study,(12) two rats were placed in a small cage and then given minor electric shocks. As a result of these shocks, the rat would become agitated and attack the second rat. Twelve minutes before this experiment, GHK-Cu peptide was administered to both rats. Researchers noted that the number of attacks, following electric shocks, was reduced 5-fold from usual.

A study has investigated the potential of Glycyl-L-histidyl-L-lysine (GHK) to regulate the presence of reactive oxygen species (ROS) within laboratory cells, with a focus on its ability to mitigate oxidative stress through interactions with various types of ROS.(13) It is proposed that GHK acts as an endogenous antioxidant, potentially due to its selective targeting and neutralization of certain radicals, specifically hydroxyl (·OH) and peroxyl (ROO·) radicals. GHK's antioxidant properties were evaluated using two main techniques: flow cytometry, a method for analyzing various cellular characteristics, and electron spin resonance (ESR) spin trapping, which is employed to detect free radicals. Throughout these evaluations, GHK appeared to reduce ROS levels induced by tert-butyl hydroperoxide (t-BOPD), a chemical known to promote oxidative stress within cells. ESR data revealed that GHK was notably positive in reducing concentrations of ·OH and ROO· radicals, although it had an apparently modest action on superoxide (O2 -·) radicals. Further examinations using ESR evaluated GHK's relative potential to neutralize ·OH radicals compared to other antioxidants such as carnosine and reduced glutathione (GSH), both recognized for their antioxidant capabilities. Preliminary results suggest that GHK could be more proficient in neutralizing ·OH radicals compared to these alternatives.

A study has investigated the possible mechanisms through which the GHK-Cu peptide complex might influence anti-inflammatory actions, particularly against lung tissue inflammation induced by cigarette smoke (CS).(14) It is hypothesized that GHK-Cu may influence various biochemical pathways and molecular markers related to inflammation and oxidative stress, although specific mechanisms remain somewhat uncertain. In experiments with mouse models exposed to CS, exposure to GHK-Cu was linked to a potential decrease in the production of pro-inflammatory cytokines, including interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α), found in bronchoalveolar lavage fluid, fluid used to capture cells and soluble factors from airways and lung tissues. These results tentatively suggest that GHK-Cu might help mitigate inflammatory responses triggered by cigarette smoke. Furthermore, a potential reduction in myeloperoxidase (MPO) activity, an enzyme serving as a marker for neutrophil-driven inflammation and oxidative stress, was observed in lung tissues receiving GHK-Cu exposure. This observation could indicate a potential role of GHK-Cu in limiting neutrophil activation or mobilization, possibly reducing oxidative bursts and consequent inflammation. At the molecular level, research proposes that GHK-Cu may interact with the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling pathway. NF-κB plays a critical role in initiating and perpetuating inflammation. It is believed that the peptide complex possibly inhibits NF-κB activation by affecting the phosphorylation of IκBα, a protein that inhibits NF-κB. This interaction could hypothetically result in lower expression of genes promoting inflammation, controlled by NF-κB. Additionally, the study suggests that GHK-Cu might potentially influence the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway. Nrf2 is integral to cellular defenses against oxidative damage. It is postulated that GHK-Cu possibly increases Nrf2 expression and nuclear translocation in lung tissues, thus promoting transcription of genes combating oxidative stress and possibly enhancing cellular resistance against oxidative damage. Research further examines how GHK-Cu interacts with oxidative stress markers, such as malondialdehyde (MDA) and glutathione (GSH). MDA is a product of lipid peroxidation and an indicator of oxidative stress, while GSH is a vital antioxidant playing a crucial role in cellular defense mechanisms. Experimentation with GHK-Cu is associated with a tentative reduction in MDA levels and a potential restoration of GSH levels, suggesting a potential ameliorative action on oxidative stress.

A theoretical model postulates that GHK might play a role in mitigating iron discharge from ferritin.(15) Ferritin, a protein complex that stores iron, releases it in a form that can facilitate lipid peroxidation, a process where free radicals attack lipids, leading to cellular damage. It is suggested that GHK might inhibit the assembly of iron complexes within injured tissues, which could, in turn, decrease inflammation. Further exploration of GHK's role reveals that it may interact with specific biological pathways governing iron release from ferritin. This interaction could restrict iron release by up to 87%, although this is a provisional estimate. Such a significant reduction in iron release could conceivably decrease both inflammation and oxidative stress, the latter being a condition where harmful oxidative processes occur faster than the body's ability to counteract them, in affected tissues.