GHK-Cu, or glycyl-L-histidyl-L-lysine copper , is a naturally occurring tripeptide first isolated in 1973 from human plasma. Composed of the amino acids glycine, histidine and lysine, this peptide has a strong affinity for copper ions, forming a complex known as GHK-Cu. Initially discovered for its ability to make old human liver tissue synthesize proteins like younger tissue, the presence of GHK in human body fluids such as plasma, saliva and urine suggests its involvement in natural tissue healing and maintenance.

Studies over the years have shown that the GHK-Cu peptide plays a significant role in wound healing, skin care, cosmetics and anti-aging treatments. It is known to accelerate regeneration processes, enhance antioxidant and anti-inflammatory responses, and improve the bioavailability of copper, which is important for various metabolic functions. GHK's ability to bind copper not only helps regulate copper metabolism, but also makes it an essential component of cellular activity that facilitates tissue healing and repair.

Since its discovery, the GHK-Cu peptide has been widely used in cosmetic and medical products for skin and hair care. Its effectiveness is attributed not only to its copper-binding properties, but also to its effect on gene expression. The GHK-Cu peptide is also being studied for its potential therapeutic applications against age-related conditions such as neurodegeneration and cognitive decline.

GHK-Cu peptide for tissue repair and wound healing

The GHK-Cu complex plays a significant role in tissue remodeling, skin repair and wound healing by promoting various biological processes necessary for recovery from injury. In a comprehensive analysis by Pickart (2008), the peptide increased the recruitment of key repair cells such as macrophages and capillary cells to the wound site [1]. It promoted the inflammatory response, helped remove damaging factors such as free radicals, and promoted the repair process by modulating the synthesis of collagen, elastin and other important proteins needed to rebuild tissue structure. Moreover, GHK-Cu stimulated the production of growth factors such as vascular endothelial growth factor and nerve growth factor, helping to improve angiogenesis, nerve growth and skin elasticity [1].

The anti-inflammatory properties of GHK-Cu are significant; it reduces oxidative factors and increases the production of antioxidants such as superoxide dismutase. In addition, it improves blood flow to damaged areas by dilating blood vessels. At the cellular level, GHK-Cu stimulates the production of growth factors - such as vascular endothelial growth factor and fibroblast growth factor - which are important for increasing cell proliferation, nerve regeneration, angiogenesis and improving the health and size of hair follicles [1]. In a laboratory setting, GHK-Cu treatment has been shown to significantly increase the proliferation of keratinocytes - key skin barrier cells [2]. Techniques such as hematoxylin and eosin staining, immunohistochemistry and western blot analysis confirmed an increase in markers related to cell proliferation and survival. In addition, levels of proliferating cell nuclear antigen (PCNA) and stem cell markers such as p63 increased under GHK-Cu, indicating enhanced regenerative capacity. Expression of integrins, key to cell adhesion and signaling, was also increased, further supporting the peptide's role in skin integrity and repair [2].

Moreover, another study focused on the therapeutic benefits of GHK-Cu encapsulated in liposomes, particularly its effects on endothelial cell growth and burn wound healing in mice [3]. Encapsulation in nanoscale liposomes led to a significant 33.1% increase in the growth rate of human umbilical vein endothelial cells (HUVECs). These are cells that lining blood vessels and are important for the formation of new blood vessels during the healing process. Flow cytometry also showed changes in the cell cycle, with more cells in the G1 phase and fewer in the G2 phase, indicating accelerated cell cycle progression. In addition, Western blotting revealed that GHK-Cu liposome treatment increased the levels of proteins important for vascular and tissue growth, such as vascular endothelial growth factor and fibroblast growth factor-2, along with the cell cycle proteins CDK4 and cyclin D1. The study showed that the liposome-encapsulated peptides helped cells go through the growth cycle more efficiently [3]. In another study on a burn wound model in mice, GHK-Cu liposomes significantly promoted angiogenesis compared to free GHK-Cu, with a significant increase in the expression of CD31 and Ki67, markers of vascular and cellular proliferation [4]. Increased angiogenesis contributed to faster healing, reducing recovery time to just 14 days after injury. These results point to GHK-Cu liposomes as a valuable option for improving skin wound healing. They offer faster recovery times and promote the body's natural repair processes, making them a promising option for medical and potentially cosmetic applications where rapid skin repair is desired.

Moreover, during an in-depth study of the therapeutic effects of glycyl-histidyl-lysine-Cu (2+), the researcher found a link between the application of GHK-Cu and glycosaminoglycan synthesis [5]. Using experimental rat wound models and rat skin fibroblast cultures, the researchers administered repeated injections of GHK-Cu at a dose of 2 mg per injection. The results were significant: GHK-Cu clearly stimulated the production of wound tissue, as indicated by an increase in both dry weight and total protein levels. It also increased the production of type I collagen and glycosaminoglycans, with marked increases in hydroxyproline and uronic acid. Electrophoretic analysis also showed significant accumulation of chondroitin sulfate and dermatan sulfate in wound areas, while hyaluronic acid levels decreased over time [5]. These findings indicate the ability of GHK-Cu to selectively modulate key components of the extracellular matrix, enhancing tissue repair and wound healing processes. Moreover, a review of studies showed that GHK-Cu helps rejuvenate fibroblasts after their exposure to radiation and attracts immune and endothelial cells to damaged areas. As such, it can promote the repair of various tissues such as skin, hair follicles and the gastrointestinal tract [6]. In the cosmetic industry, GHK-Cu is considered a new approach to tighten sagging skin, increase elasticity and firmness, and improve the overall appearance of skin by reducing fine lines, wrinkles, sun damage and dark spots. It also promotes the growth of keratinocytes, which are essential for healthy skin [6].

GHK-Cu peptide for lung health

Numerous studies have shown that GHK-Cu peptide improves and promotes optimal lung function and protects the respiratory system from various diseases. In a study on mice with idiopathic pulmonary fibrosis (IPF), a severe lung disease characterized by progressive scarring, glycyl-L-histidyl-l-lysine combined with copper (GHK-Cu) showed significant results. Researchers evaluated the potential of GHK-Cu in the treatment of IPF and pulmonary fibrosis in a mouse model [7]. In this model, GHK-Cu was administered to mice at various doses, showing promising therapeutic effects by enhancing the regeneration of lung tissue. Specifically, the treatment led to a reduction in inflammatory cytokines, a decrease in the activity of harmful enzymes in the lungs and less collagen deposition, a hallmark of fibrosis. GHK-Cu was also found to restore the balance between molecules that break down and inhibit excessive tissue growth, and to help alleviate the process by which epithelial cells go into a state that contributes to fibrosis. Modulation of several key signaling pathways involved in inflammation and fibrosis highlights the

potential of GHK-Cu as a new treatment option for IPF. Another study simulated IPF in mice using intratracheal injections of bleomycin followed by alternate treatment with GHK [8]. The efficacy of GHK was evaluated by studying lung tissue responses, including inflammation and collagen deposition, which are important in the development of fibrosis. The results showed that GHK significantly reduced signs of inflammation and fibrosis in the lungs. It reduced the thickness of the interstitial area of the lung, decreased collagen deposition and lowered the levels of key markers of inflammation and fibrosis [8]. These findings suggest that GHK can potentially reverse or block the progression of IPF by affecting key biochemical pathways involved in the disease process.

Moreover, the GHK-Cu peptide showed beneficial effects in the treatment of acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). In laboratory experiments, GHK-Cu treatment significantly reduced reactive oxygen species (ROS) and increased superoxide dismutase (SOD) activity in cells exposed to lipopolysaccharide (LPS), a common experimental method of inducing inflammation. In addition, GHK-Cu reduced key inflammatory cytokines in these cells, which is important for managing the inflammatory response [9]. In a mouse model, GHK-Cu treatment reduced lung tissue damage and inflammation, suggesting that it helps preserve lung structure and function during ALI. These findings indicate that GHK-Cu may be a new approach to treat ALI and ARDS [9]. Moreover, due to its regenerative, antioxidant and anti-inflammatory properties, GHK-Cu has shown potential results in the treatment of chronic obstructive pulmonary disease (COPD) [10]. COPD is characterized by persistent airflow limitation and chronic inflammation, often exacerbated by environmental factors such as cigarette smoke. Researchers examined the effects of GHK-Cu on emphysema induced by cigarette smoke exposure in mice. For 12 weeks, mice exposed to cigarette smoke were given GHK-Cu, which reduced lung damage and the imbalance between destructive enzymes and their inhibitors in the lungs. It also lowered levels of inflammatory cytokines and oxidative stress markers, while promoting the body's antioxidant defenses. Further in vitro tests on human lung cells confirmed GHK-Cu's ability to alleviate oxidative stress, suggesting its efficacy in the treatment of emphysema [10]. These findings underscore the potential of GHK-Cu as a therapeutic approach for COPD, particularly in the treatment of cigarette smoke-induced emphysema through its combined anti-inflammatory and antioxidant effects.

What's more, another study showed that GHK-Cu peptide helps resolve skeletal muscle dysfunction associated with chronic obstructive pulmonary disease. The results showed that treating muscle cells and mice exposed to smoke with GHK-Cu helped reduce muscle degradation caused by smoke exposure. In addition, GHK-Cu treatment improved muscle function and reduced signs of muscle breakdown by activating specific pathways that protect against muscle degradation and enhance antioxidant defenses [11]. These findings underscore the potential of GHK-Cu as a therapeutic agent to help manage muscle dysfunction in COPD patients. In another study of permanent airflow obstruction (FAO), a condition often seen in severe asthma, GHK-Cu treatment significantly reduced airway scarring, mucus secretion and other FAO-related changes. These benefits are largely due to GHK-Cu's ability to reduce factors that promote inflammation by enhancing the function of SIRT1, a protein that helps protect cells from damage [12]. This study suggests that GHK-Cu may be a promising drug for reducing airway remodeling in asthma, potentially improving lung function and symptoms in patients with FAO.

GHK-Cu peptide to promote graft healing in ACL reconstruction

The process of graft healing after anterior cruciate ligament reconstruction (ACLR) is important because it significantly affects the success and durability of the operation. A scientific study examined the effect of GHK-Cu peptide on graft healing in the ACLR. The experiment involved seventy-two rats divided into three groups, each receiving different treatments: saline, a low dose of GHK-Cu (0.3 mg/ml) and a high dose of GHK-Cu (3 mg/ml). Starting from the second week after surgery, treatment was administered weekly for four weeks. Early results, after six weeks, showed that the GHK-Cu-treated groups exhibited significantly less knee limp than the saline group, indicating greater joint stability. However, these differences disappeared after 12 weeks, with no sustained advantage in joint stability, graft stiffness or other measured parameters. This suggests that although GHK-Cu may temporarily improve healing after ACLR, its benefits do not persist after treatment [13].

Enhancement of skin resurfacing with GHK-Cu peptide (human study)

In a case study, a cosmetic mixture containing GHK-Cu, oligo-hyaluronic acid, rhodiolar extract, tranexamic acid and β-glucan was applied using the Jet-M device to a 59-year-old man in a series of weekly sessions for three months [14]. Importantly,

The procedure did not require anesthesia and was painless. The result was a visible improvement in skin texture and a reduction in wrinkles around the treated eye area, as evidenced by clinical photographs. In addition, skin biopsies from treated and untreated areas showed increased collagen production in the treated skin. In addition, increased levels of collagen IV, fibrillin-1, procollagen type 1 and tropoelastin were also observed, indicating increased synthesis of structural proteins in the skin. Importantly, there were no side effects during or after the treatment sessions, demonstrating the safety and efficacy of combining GHK-Cu with Jet-M technology for cosmetic skin improvement.

Enhancement of glycosaminoglycan synthesis with GHK-Cu peptide

In the study, fibroblasts were treated with different concentrations of GHK-Cu peptide. The researchers monitored glycosaminoglycan synthesis by measuring the incorporation of radioactively labeled glucosamine and sulfate into glycosaminoglycans taken from the culture medium and cell layer. The results showed that GHK-Cu stimulates glycosaminoglycan synthesis in a dose-dependent manner, with the greatest increase at very low concentrations (10^(-9) to 10^(-8) M). Above these concentrations, glycosaminoglycan synthesis levels returned to those observed in untreated control cultures [15]. Further analysis of the types of glycosaminoglycans showed that GHK-Cu mainly increased the production of dermatan sulfate in the extracellular space and heparan sulfate in the cell layer. Interestingly, it had no effect on hyaluronic acid synthesis.

GHK-Cu peptide as an activator of wound repair

During the in vivo wound chamber model in rats, stainless steel mesh cylinders were implanted under the skin to simulate a controlled wound environment. Rats were injected with saline (control) or GHK-Cu into these chambers. At the end of the experiment, the chambers were examined for various biomarkers indicative of healing, including total protein, collagen and glycosaminoglycans [16]. The study showed that GHK-Cu significantly increased dry weight, DNA, total protein and especially collagen in the treated chambers compared to the control group. The increase in collagen was significantly double that of non-collagenous proteins. These findings demonstrated that GHK-Cu plays a significant role in promoting the synthesis of key extracellular matrix components necessary for wound healing. A marked increase in the types of collagen produced and a noticeable accumulation of dermatan sulfate were also observed, although there were no changes in TGF-beta mRNA levels. These results definitely

confirm the effectiveness of GHK-Cu in increasing the accumulation of essential matrix components in wounds.

GHK-Cu peptide in the prevention of sleep deprivation-induced memory disorders

Sleep deprivation can impair memory and contribute to neurodegenerative diseases by inducing inflammation and cellular damage. A study to test the potential of GHK-Cu peptide against memory impairment in mice found significant results. Mice treated with GHK did not show the learning deficits observed in the control group, which received saline. Moreover, GHK effectively reduced MCP-1 and nitrotyrosine levels in the hippocampus - markers associated with inflammation and cellular stress, respectively. By lowering these markers, GHK helped protect against cognitive decline typically induced by short-term sleep deprivation by targeting underlying inflammatory processes and oxidative stress [17]. These findings indicate the potential of GHK as a therapeutic agent in neuroprotection and underscore its importance in maintaining learning and memory under adverse conditions.

GHK-Cu peptide for age-related cognitive decline

GHK-Cu has been identified as a potential treatment for cognitive impairment associated with aging. In a study involving aged C57BL/6 mice, GHK-Cu was administered intranasally at a dose of 15 mg/kg per day for two months to evaluate its effects on cognitive function [18]. The results showed that treated mice showed significant improvements in tasks measuring spatial memory and navigation compared to a control group that received saline. They also showed lower levels of neuroinflammation and axonal damage, indicating the neuroprotective properties of GHK-Cu. These results underscore the ability of GHK-Cu to increase the brain's resistance to the effects of aging and suggest further research opportunities. The use of intranasal administration, particularly via an atomizer, provides a practical method of administering this peptide in both preclinical and potential clinical settings.

GHK-Cu peptide in the treatment of neurodegenerative diseases

Neurodegeneration, characterized by progressive neuronal dysfunction and cognitive decline, is a major challenge, especially among the elderly. In the study, the GHK-Cu peptide was administered to 5xFAD transgenic mice, commonly used in

Alzheimer's disease studies, starting at 4 months of age [19]. Mice with AD received intranasal doses of GHK-Cu at 15 mg/kg three times a week for three months. The treatment was found to delay cognitive impairment, reduce amyloid plaque formation and reduce inflammation in important brain areas such as the frontal cortex and hippocampus. These preliminary results support further research into the potential of GHK-Cu as an effective neurotherapeutic agent in Alzheimer's disease, targeting multiple aspects of the disease's pathology. Moreover, the GHK-Cu peptide modulates gene expression, potentially resetting the expression of old and diseased genes to healthier states. This ability was demonstrated in studies using the Broad Institute Connectivity Map, revealing a significant effect of GHK on the expression of genes important for neuronal health. GHK promotes collagen synthesis, angiogenesis, and exhibits anti-inflammatory and neuroprotective effects, which may alleviate symptoms of neurodegenerative diseases [20]. In addition, oxidative stress, impaired copper homeostasis and inflammation due to excess pro-inflammatory cytokines are key factors in age-related neurodegenerative diseases. The role of deleterious epigenetic changes in aging further underscores the need for interventions targeting these pathways. Compounds such as the GHK-Cu peptide, which can restore copper balance, reduce inflammation and improve gene function, are seen as promising solutions for preventing cognitive decline and treating neurodegenerative disorders [21]. Moreover, neurodegenerative diseases are often associated with oxidative stress, inflammation and abnormal protein folding, exacerbated by excess metal ions such as copper and zinc, which promote protein aggregation and cell toxicity. GHK-Cu has shown potential against oxidative stress and protects against cell death and protein aggregation caused by these metals. Studies have shown that GHK not only inhibits, but can reverse protein aggregation such as that observed with bovine serum albumin (BSA) under inflammatory conditions. It also reduces the increased toxicity of compounds such as paraquat in combination with copper [22]. These properties make GHK a promising candidate for further research into its protective abilities against metal toxicity and its therapeutic potential in the treatment of neurodegenerative diseases.

GHK peptide in the treatment of diabetes complications

Patients with diabetes often face slower wound healing due to prolonged high blood sugar levels, which impairs the function of white blood cells and leads to nutrient deficiencies in cells, increasing the risk of infection. W

The study tested a new approach using biotinylated GHK peptide (BioGHK) in combination with collagen (termed Peptide Incorporated Collagen-PIC) to improve wound healing in rats with diabetes. The study compared rats with diabetes treated with PIC with rats with a standard collagen film (CF) and an untreated group. The study measured the rate of wound closure and the biochemical composition of the healing tissue, including levels of collagen, uronic acid, proteins and DNA. Nitric oxide and skin antioxidants such as glutathione (GSH) and ascorbic acid were also tracked. The results showed that the PIC group healed significantly faster, with better antioxidant levels compared to both the control and CF groups. Additional in vitro tests showed that PIC promotes fibroblast growth, which is essential for skin repair. Histological examination also showed better tissue repair, more collagen and active participation of fibroblasts and mast cells in PIC-treated wounds, supporting the use of BioGHK collagen to improve diabetic wound healing [23].

GHK-Cu peptide for diabetic neuropathic ulcers (human study)

Another comprehensive clinical trial tested the safety and efficacy of a complex of glycyl-L-histidyl-L-lysine and copper (known as Lamin Gel) on diabetes-related neuropathic ulcers. Participants in the study received standard wound care, which included thorough wound cleaning, daily treatment with the drug, use of specialized footwear to reduce pressure, and education on diabetes care. The study showed that the use of Lamin Gel significantly improved the healing of foot ulcers, with a median area closure of 98.5% compared to 60.8% in the placebo group. The gel was particularly effective in treating larger ulcers and showed a higher percentage of wound closure. Treatment with Lamin Gel also resulted in a significantly lower infection rate compared to the placebo group, indicating its potential not only in accelerating healing, but also in preventing further complications. These results underscore the promise of lamin Gel as a potent treatment option for diabetes-related neuropathic ulcers, surpassing standard care in efficacy [24]. In addition, a preliminary study examined the effects of glycyl-L-histidyl-L-lysine (GHK) copper chelate, specifically Lamin® treatment, on the healing of diabetic ulcers. This open-label, early-phase study used different concentrations of the tripeptide copper chelate GHK-L-Histidyl-L-L-Lysine (PC1020) to evaluate its efficacy in wound healing. Diabetic ulcers were treated with injections of 0.03%, 0.3% or 3.0% concentrations of PC1020 or saline directly into the ulcers for two weeks. The study showed that the group treated with 0.3% PC1020 had a significantly better wound closure rate compared to the saline group, with a noticeable improvement in the

healed wound surface at the end of the treatment and follow-up period. These results suggest that GHK copper chelate may be a promising therapeutic agent for the treatment of diabetic ulcers [25].

GHK for intracerebral hemorrhage

Intracerebral hemorrhage (ICH) is a serious type of stroke known for high mortality and disability. A scientific study examined the efficacy of GHK-Cu peptide in treating ICH. Administered at doses of 5 and 10 μg/g to rats affected by ICH, GHK showed significant improvement in neurological recovery. This was evidenced by reduced brain swelling, better neurological performance and higher neuronal survival rates. The researcher also found increased neuronal integrity. In addition, GHK reduced inflammation and adjusted the levels of key enzymes involved in maintaining the extracellular matrix, which is important for reducing secondary damage after ICH. The study also noted that the effects of GHK are partially mediated by the PI3K/AKT pathway. These findings suggest that GHK may be an innovative therapeutic strategy to improve outcomes in patients suffering from ICH [26].

Topical GHK-Cu peptide in ischemic wound healing

Researchers examined the therapeutic effects of topical glycyl-L-histidyl-L-lysine-copper complex (TCC; Iamin 2% Gel) on ischemic wounds in twenty-four adult male Sprague-Dawley rats. The rats were divided into three groups: one treated with topical TCC, one with TCC vehicle (gel base) and a control group receiving no treatment. At 13 days, the TCC-treated group showed a significantly faster reduction in wound size compared to the vehicle and control groups. At the end of the study, the wound area in the TCC group decreased by about 64.5%, significantly more than the 45.6% in the carrier group and 28.2% in the control group. In addition, biopsies showed that wounds treated with TCC had significantly lower levels of inflammatory markers and enzymes associated with tissue breakdown than control wounds. These findings underscore the potential of topical TCC treatment to significantly accelerate ischemic wound healing [27].

GHK peptide for heart protection

In a scientific study, the recombinant GHK peptide was tested using a model of the striped danio to evaluate its potential to mitigate cardiotoxic effects induced by copper exposure. It is noteworthy that even at a minimum concentration of 1 nM, GHK-Cu complexes significantly reduced cardiotoxicity symptoms such as slow heart rate and

irregular heartbeat, without affecting other cardiac functions in striped danio larvae exposed to Cu(II). The study showed that recombinant GHK tripeptides have high affinity for copper ions and can effectively protect against copper-induced cardiotoxicity without altering other cardiovascular parameters. This study suggests that these specially made GHK peptides may be a new way to treat or prevent cardiac damage caused by copper toxicity [28].

5-ALA and GHK peptide complex in the treatment of alopecia areata (human study)

The scientific study looked at a new treatment for male pattern baldness, combining 5-aminolevulinic acid (5-ALA) with a GHK peptide in a product called ALAVAX. In a six-month clinical trial involving forty-five men, participants were divided into three groups. Each group used different concentrations of ALAVAX or placebo daily. Results showed that the group using a medium concentration of ALAVAX (50 mg/mL) reported a significant increase in hair count after six months compared to the groups using a higher concentration or placebo [29]. In addition, patients reported high satisfaction with the treatment, especially those who used the higher concentration of ALAVAX, although there were no significant changes in hair length or thickness between groups. Importantly, none of the participants reported side effects, highlighting the safety of the treatment. This suggests that the combination of 5-ALA and GHK peptide may be a promising new treatment option for hair loss without causing side effects.

Cosmetic benefits of GHK-Cu peptide (review of human studies)

Several studies have shown that GHK-Cu peptide can significantly improve the appearance of aging skin [30]. For example, in one study, 71 women used a face cream with GHK-Cu for 12 weeks. They noticed that their skin became thicker and denser, less saggy, clearer and smoother, with fewer fine lines and wrinkles. In another study, 41 women used an eye cream with GHK-Cu for 12 weeks. The cream worked better than placebo and vitamin K cream in reducing the appearance of lines and wrinkles, improving the appearance of the skin, and increasing the density and thickness of the skin around the eyes. GHK-Cu was also tested on the skin of the participants' thighs for 12 weeks, where it increased collagen production in 70% women, a better result than using vitamin C or retinoic acid creams. Using the GHK-Cu cream twice a day for 12 weeks improved sagging, clarity, firmness and overall appearance of the skin, while stimulating skin cell growth. A pilot study confirmed

these benefits, noting that topical application of copper tripeptide complexes improved skin thickness, hydration, elasticity and collagen production, leading to smoother and more even skin. What's more, a clinical trial involving women using GHK-Cu in nano-lipid carriers twice daily for eight weeks showed a significant reduction in wrinkle volume and depth, performing better than control serums and another popular anti-aging product, Matrixyl® 3000. These findings underscore the potential of GHK-Cu peptide as an effective anti-aging skincare ingredient [30].

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Disclaimer

This article was written for educational purposes and is intended to raise awareness of the substance being discussed. It is important to note that the substance discussed is a substance, not a specific product. The information contained in the text is based on available scientific research and is not intended to serve as medical advice or promote self-medication. The reader should consult any health and treatment decisions with a qualified health professional.