GHK-Cu Peptide Investigations

Three amino acids and the copper ion make up the tiny peptide Glycyl-L-Histidyl-L-Lysine-Copper. Dr. Loren Pickart of UC San Francisco’s biochemistry department made the first discovery in the 1970s. After finding GHK-Cu in plasma, Dr. Pickart expanded his discovery to include GHK-Cu in various bodily tissues and organs. He reasoned that peptides could be involved in cell aging after suggesting that GHK-Cu levels drop. Many studies have looked at the potential effects of GHK-Cu throughout the years. As a bonus, it has been hypothesised to increase collagen formation and skin suppleness while acting as an antioxidant, anti-inflammatory, and wound healer.

Neuroprotective properties of GHK-Cu suggest it may be useful in the context of neurological disorders, including Alzheimer’s and Parkinson’s. Furthermore, the anti-cancer potential of GHK-Cu has been studied. Research suggests it may potentially boost immune cell activity while preventing the development of certain cancer cells. 

What Makes Copper So Special?

The physiologically active version of the peptide, known as the GHK-Cu complex, is formed when copper is added to the GHK peptide. The biological activity of this complex is greatly influenced by the copper ion, which is an integral part of it. GHK-Cu has been suggested to have various biological effects, including increasing antioxidant activity, fostering the creation of renewed blood vessels, and increasing collagen synthesis. As a cofactor for enzymes implicated in collagen formation, angiogenesis, and antioxidant defense, copper plays an essential role in these processes.

Furthermore, the antioxidant enzyme superoxide dismutase (SOD) relies on copper for its function in removing potentially dangerous free radicals from the organism. Research suggests that GHK-Cu may protect against oxidative stress and age-related damage by increasing the activity of SOD.

Additionally, copper can alter immunological responses and is a powerful agent against inflammation. Copper is believed to regulate immune cell activity and cytokine synthesis, which may explain why GHK-Cu has been speculated to have anti-inflammatory properties. When added to the GHK peptide, copper may increase its biological activity.

GHK-Cu: Mechanism of Action

Research suggests several routes may be involved in the complicated mechanism of action of GHK-Cu. Among the most important ways that GHK-Cu has been hypothesized to exert its effects are:

• Studies suggest that one property of GHK-Cu is that it may promote collagen formation. Collagen is the principal structural protein in connective tissues, skin, and bones. It is believed that certain signaling pathways and growth factors are activated to bring about this effect.
• Research suggests GHK-Cu may elevate antioxidant activity by boosting the performance of enzymes, including catalase and superoxide dismutase (SOD). This may aid in lowering oxidative stress and neutralizing free radicals.
• GHK-Cu has been hypothesized to have anti-inflammatory properties by regulating immune responses and decreasing the generation of cytokines that promote inflammation.
• Findings imply that GHK-Cu may stimulate angiogenesis, producing new blood vessels crucial for wound healing and tissue repair.
• GHK-Cu has been speculated to have neuroprotective properties, which may include lowering oxidative stress and increasing the activity of certain growth factors in the brain.
• Studies have suggested that GHK-Cu may modulate the expression of genes involved in immunological regulation, antioxidant defense, collagen formation, and other biological processes.

Scientists assume that many of GHK-Cu’s properties may be due to its complex mode of action.

GHK-Cu Peptide and Collagen Synthesis

Studies suggest there are several ways in which GHK-Cu might increase collagen synthesis. One important strategy is potentially stimulating collagen production via certain growth factors and signaling pathways. Studies have purported that GHK-Cu might activate enzymes necessary for collagen formation and upregulate gene expression.

Furthermore, research has indicated that GHK-Cu may boost collagen production by activating fibroblast cells. The process involves boosting collagen and other extracellular matrix protein synthesis by fibroblasts, which it does by encouraging their proliferation. Matrix metalloproteinases (MMPs) and other collagen-degrading enzymes seem to have their activity regulated by GHK-Cu. GHK-Cu appears to aid in preserving collagen and its subsequent production by blocking the action of relevant enzymes.

GHK-Cu Peptide and Wrinkles

Because it may promote collagen production and skin regeneration, GHK-Cu has been hypothesized to diminish the depth of wrinkles and fine lines. To do this, GHK-Cu is assumed to stimulate the skin’s natural creation of collagen and other extracellular matrix components by activating growth factors and signaling pathways. Fibroblasts produce the extracellular matrix proteins; GHK-Cu also seems to boost their activity. Enhanced fibroblast activity has the potential to rejuvenate skin cells and regulate inconsistencies along the skin surface.

Glycosaminoglycans (GAGs) are an essential part of the skin’s extracellular matrix, and research has hinted that GHK-Cu may increase their synthesis. GAGs hydrate and support the skin structure.

In addition to its possible antioxidant and anti-inflammatory properties, studies suggest GHK-Cu may shield the skin against environmental aggressors that have a role in the onset of wrinkles and fine lines. Findings imply the potential of GHK-Cu to enhance the expression of certain genes associated with antioxidant and anti-inflammatory pathways might account for some of these properties.

GHK-Cu and the Brain

Multiple pathways have been identified by which GHK-Cu may exert its neuroprotective potential. Improving the brain’s antioxidant defenses is important in preventing neuron oxidative damage. Research has suggested that GHK-Cu may enhance the function of antioxidant enzymes like superoxide dismutase (SOD) and decrease the generation of neurotoxic reactive oxygen species (ROS). Furthermore, it seems that GHK-Cu may have anti-inflammatory properties, which may aid in protecting neurons from damage caused by inflammation. Inflammatory enzymes such as cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) may inhibit their activity by GHK-Cu.

Plus, research has purported that GHK-Cu may boost the synthesis of certain signaling molecules and growth factors that play a role in neuronal development and regeneration. Neuronal survival and function may both be enhanced by this uptick in output. In addition to its antioxidant and anti-inflammatory potential, GHK-Cu has been theorized to possess chelating properties, which might allow it to bind to and eliminate neurotoxic metals. Researchers speculate that metals, including copper, iron, and zinc, may have their neurotoxic effects mitigated by GHK-Cu binding.

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References

• [i] Pickart L, Margolina A. Regenerative and Protective Actions of the GHK-Cu Peptide in the Light of the New Gene Data. Int J Mol Sci. 2018;19(7):1987. Published 2018 Jul 7. doi:10.3390/ijms19071987

• [ii] Pickart L, Vasquez-Soltero JM, Margolina A. GHK-Cu may Prevent Oxidative Stress in Skin by Regulating Copper and Modifying Expression of Numerous Antioxidant Genes. Cosmetics. 2015; 2(3):236-247. https://doi.org/10.3390/cosmetics2030236

• [iii] Wen-hui Ma, Meng Li, Hai-feng Ma, Wei Li, Li Liu, Yan Yin, Xiao-ming Zhou, Gang Hou, Protective effects of GHK-Cu in bleomycin-induced pulmonary fibrosis via anti-oxidative stress and anti-inflammation pathways, Life Sciences, Volume 241, 2020,117139, ISSN 0024-3205, https://doi.org/10.1016/j.lfs.2019.117139.

• [iv] Dou Y, Lee A, Zhu L, Morton J, Ladiges W. The potential of GHK as an anti-aging peptide. Aging Pathobiol Ther. 2020 Mar 27;2(1):58-61. doi: 10.31491/apt.2020.03.014. PMID: 35083444; PMCID: PMC8789089.

• [v] Sahu R, Yadav S, Gunturu KC, Kapdi AR. Phenothiazine-Based Cu(II)-Selective Fluorescent Sensor: GHK-Cu Sensing Applications. J Org Chem. 2023 Nov 3;88(21):15118-15129. doi: 10.1021/acs.joc.3c01600. Epub 2023 Oct 13. PMID: 37830186.

• [vi] Park JR, Lee H, Kim SI, Yang SR. The tri-peptide GHK-Cu complex ameliorates lipopolysaccharide-induced acute lung injury in mice. Oncotarget. 2016 Sep 6;7(36):58405-58417. doi: 10.18632/oncotarget.11168. PMID: 27517151; PMCID: PMC5295439.

• [vii] Jiang F, Wu Y, Liu Z, Hong M, Huang Y. Synergy of GHK-Cu and hyaluronic acid on collagen IV upregulation via fibroblast and ex-vivo skin tests. J Cosmet Dermatol. 2023 Sep;22(9):2598-2604. doi: 10.1111/jocd.15763. Epub 2023 Apr 16. PMID: 37062921.

• [viii] Pickart L, Vasquez-Soltero JM, Margolina A. The human tripeptide GHK-Cu in prevention of oxidative stress and degenerative conditions of aging: implications for cognitive health. Oxid Med Cell Longev. 2012;2012:324832. doi: 10.1155/2012/324832. Epub 2012 May 10. PMID: 22666519; PMCID: PMC3359723.