GHK-Cu Peptide: Mechanisms of Action and Research Applications

Introduction to GHK-Cu

GHK-Cu is a naturally occurring copper complex first identified in human plasma, with subsequent detection in saliva and urine. Copper peptides are small, naturally occurring protein fragments that exhibit a high affinity for copper ions, which are critical to normal physiological function. Research indicates that GHK-Cu serves multiple roles in the human body, including promoting activation of wound healing, attracting immune cells, exerting antioxidant and anti-inflammatory effects, stimulating collagen and glycosaminoglycan synthesis in skin fibroblasts, and promoting blood vessel growth.

Evidence suggests that GHK-Cu acts as a feedback signal generated after tissue injury. Initially, it appears to function as a potent protector of tissue and an anti-inflammatory agent that controls oxidative damage occurring post-tissue injury. Subsequently, it plays a significant role in signaling tissue remodeling, which removes damaged or scarred tissue and generates new, healthy tissue. However, these positive effects decline with age because the concentration of GHK-Cu in the body decreases over time. Consequently, there is an observed increase in inflammation, cancerous activity, and tissue destruction.

Mechanism of Action

GHK-Cu exerts its effects on a variety of pathways in the human body due to the peptide sequence and copper’s ability to promote diverse functions. At the site of tissue injury, studies indicate that GHK-Cu acts as a potent chemoattractant for mast cells and macrophages, among others, which promote the release of proteins that stimulate tissue growth and repair. As noted, research suggests GHK-Cu operates in a dual manner to remove scar tissue from injured locations and replace it with new tissue. Primarily, it acts directly on fibroblasts by increasing the production of mRNA and protein for collagen, elastin, proteoglycans, glycosaminoglycans, and decorin—all critical components in tissue repair and maintenance. Furthermore, it stimulates the production of metalloproteases and protease inhibitors, which function to remove damaged tissue proteins. It also reduces the secretion of TGF-beta from fibroblasts during this process, as TGF-beta acts to induce scar formation.

Research also demonstrates that GHK-Cu increases collagen synthesis by chondrocytes within bone. This leads to enhanced growth of human marrow stromal cells and attachment of osteoblastic cells, which promote bone growth and formation. It also provides a source of copper for blood vessels during the process of angiogenesis in tissues. Because angiogenesis cannot occur without a proper copper depot, the presence of GHK-Cu in growing tissue is considered essential for survival. Studies have further shown that GHK-Cu has the ability to increase differentiation and proliferation of axons within neurons, indicating an effect on the nervous system to ensure proper functionality. GHK-Cu blocks ferritin channels and the release of tissue-damaging free (oxidative) iron after tissue injury, thereby blocking iron-catalyzed lipid peroxidation that occurs post-injury. This mechanism of copper-peptide-induced tissue repair appears to function for skin, hair follicles, the stomach lining, the intestinal lining, bone tissue, and hooves and fingernails.

Research Findings

Scientific research has revealed that GHK-Cu affects the following areas:

• Wound healing
• Infection control
• Hair growth restoration
• Facial cosmetic use
• Anti-cancer effects
• Cognitive health

Wound Healing and Infection Control

Multiple studies have shown the profound effects of GHK-Cu on wound healing. In the process of healing wounds, it causes better wound contraction, faster development of granular tissue, and improved angiogenesis to restore blood flow to damaged tissue. It has also been shown that systemic injection of GHK-Cu can enhance the healing process. Injection of GHK-Cu into the muscle can promote tissue repair at distant locations.

A study demonstrated that injections of GHK-Cu caused significant, systemic increases in collagen production, angiogenesis, and wound closure. A clinical trial in diabetic patients suffering from ulcerations found that when given a gel containing 2% GHK-Cu, wound closure of ulcers increased by 40% and the percentage of infection decreased by 27%, showing extremely promising results for the treatment of skin injuries that can be difficult to treat due to infection. In line with this, researchers suggest GHK-Cu could potentially be a valuable therapy given to individuals after surgery to promote wound healing, aid with pain, and prevent infection.

Anti-Inflammatory Properties

GHK-Cu also exhibits anti-inflammatory properties. A study examined GHK-Cu and its interaction with TNF-alpha along with pro-inflammatory cytokines such as IL-6 in human fibroblasts. The study indicated that GHK-Cu was able to significantly decrease the amount of inflammation. Therefore, there is a strong indication that GHK-Cu could possibly be used as either a systemic injection or topically applied therapy in the treatment of inflammatory skin conditions such as psoriasis. It was also shown that it can reduce erythema caused by UV sunlight.

Hair Growth Restoration

Research has found that GHK-Cu stimulates hair growth. Studies even showed that the efficacy of GHK-Cu for hair growth was comparable to that of 5% minoxidil, one of the most commonly used medications in the restoration of hair growth. It is commonly incorporated into hair gels and shampoos, along with other copper peptides, to restore hair growth. In fact, a commercial product known as GraftCyte, which contains GHK-Cu, was clinically evaluated and proven to improve the outcome of hair transplantation surgeries and healing. Within the hair follicle, GHK-Cu has been shown to promote collagen production and strengthen existing hair by stimulating growth in areas lacking thickness.

Facial Cosmetic Applications

The use of GHK-Cu for anti-aging cosmetics has been extensively researched and is widely used throughout the United States. When applied to the skin, studies indicate that GHK-Cu can cause firming of the skin, anti-aging effects, and anti-wrinkle activity. Multiple clinical studies have been conducted to determine the efficacy of GHK-Cu for facial treatment.

One study conducted on 20 females confirmed that GHK-Cu outperformed vitamin C and retinoic acid in increasing collagen in photoaged skin. Another clinical study performed for 12 weeks on 67 women showed that GHK-Cu significantly improved aged skin appearance, increased thickness, reduced wrinkles, and strongly induced proliferation of keratinocytes in the dermis.

Cognitive Health

Research suggests that GHK-Cu could potentially benefit cognitive health by playing a role in nerve regeneration. A study examined the effect of GHK-Cu on axons within neurons and showed that it has the ability to increase migration of hematogenous cells into collagen tubes, produce nerve growth factors, increase expression of integrins, and increase the rate of regeneration of myelinated nerve fibers. Schwann cells and axon count were also increased.

A human gene expression analysis was performed to determine the effects of GHK-Cu on gene expression, given that the molecule declines with age. It was shown that it induces a 50% or greater change of expression in 31.2% of human genes, affecting multiple biochemical pathways in organs and tissues, including the nervous system. If levels of this important peptide decline in the body with age, so will expression of necessary genes. Thus, treatment with GHK-Cu may not only directly impact physical nerve regeneration but could also impact the expression of fundamental proteins in the body.

Anti-Cancer Potential

GHK-Cu has been recommended as a treatment for metastatic cancer. A study was performed to determine gene expression of normal and cancerous cells and to identify substances that could silence genes involved in metastasis. Using a database of 7,000 genome expression profiles and treatment with 1,309 bioactive substances, it was found that only two were effective in turning down the genes overexpressed in tumor spreading; one of those was GHK-Cu. Gene control represents an exciting area of medicine, particularly in the realm of cancer therapy. Higher tissue copper may be the key to keeping cells younger, and GHK-Cu appears to be a significant mediator of this system.

Pulmonary Protection

It has been postulated that GHK-Cu could play a key role in protecting the lungs from acute injury and fibrosis. Numerous studies have been performed to determine its role, and the findings have been fairly significant. One study showed that it protects lung tissue from damage by reducing reactive oxygen species (ROS) production, increasing superoxide dismutase (SOD) activity, and decreasing TNF-α and IL-6 production through the suppression of NF-κB p65 and p38 MAPK signaling in in vitro and in vivo models of acute lung injury (ALI).

Moreover, GHK-Cu attenuated LPS-induced lung histological alterations and suppressed the infiltration of inflammatory cells into the lung parenchyma in LPS-induced ALI in mice. Taken together, these findings demonstrate that GHK-Cu possesses a protective effect in LPS-induced ALI by inhibiting excessive inflammatory responses; accordingly, it may represent a novel therapeutic approach for Acute Lung Injury and Respiratory Distress Syndrome. Further, it was shown that treatment with GHK-Cu reduces inflammatory cell infiltration and interstitial thickness in subjects with pulmonary fibrosis. It significantly improves collagen deposition and imbalances in lung tissue, and reduces TNF-alpha and IL-6 in alveolar fluid. Thus, research suggests GHK-Cu shows a strong indication for the treatment of a variety of lung diseases.

References

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• Pickart L. Compositions for accelerating wound healing in mammals containing cupric salt or complexes with amino acid or peptide. US Patent 5,164,367, 1992.
• Mulder DPM1, Gerit D.; Patt PhD2, Leonard M.; Sanders DPM, Lee; et al. (1994). "Enhanced healing of ulcers in patients with diabetes by topical treatment of glycyl-l-histidyl-l-lysine". Wound Repair Regen. 2 (4): 259–269. doi:10.1046/j.1524-475X.1994.20406.x.
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• Ahmed, M.R.; Basha, S.H.; Gopinath, D.; Muthusamy, R.; Jayakumar, R. (2005). "Initial upregulation of growth factors and inflammatory mediators during nerve regeneration in the presence of cell adhesive peptide-incorporated collagen tubes". J. Peripher. Nerv. Syst. 10 (1): 17–30. doi:10.1111/j.1085-9489.2005.10105.x.
• Pickart L; et al. The effect of the human peptide GHK-Cu on Gene Expression Relevant to Nervous System Function and Cognitive Decline.
• In Clin Exp Metastasis. 2010 Feb 9. [Epub ahead of print], a paper "A 'metastasis-prone' signature for early-stage mismatch-repair proficient sporadic colorectal cancer patients."

Reviewed by the Volta Peptides Research Team