GHK-Cu Peptide: Benefits for Skin Regeneration & Anti-Aging

Explore the transformative impact of GHK-Cu peptide on skin renewal, combating aging, and addressing cellular senescence, supported by the latest research and innovative clinical discoveries. This paves the way for innovative advancements in skin biology and the exploration of anti-aging possibilities.

Understanding GHK-Cu: The Natural Copper Peptide That Powers Skin Regeneration

The human copper-binding peptide, also known as GHK-Cu (glycyl-l-histidyl-l-lysine), is a tripeptide that is found in human plasma and is a tiny molecule. It is also capable of being released from tissues in the event of an injury. The plasma, saliva, and urine of humans all contain it in its normal state.

At the age of 20, the amount of GHK in plasma will be approximately 200 ng/mL (10−7 M), but by the age of 60, it will have decreased to 80 ng/mL. There is a correlation between the drop in the GHK level and the evident decrease in the regenerative potential of an organism.

Since being discovered in 1973, GHK-Cu has established itself as a potent element that is both protective and regenerative. The human peptide GHK-Cu was identified by a chemical reaction in human albumin which induced older human liver tissue to synthesize proteins in the same manner as younger tissue.

This activity was later shown to be a tripeptide with the amino acid sequence glycyl-L-histidyl-L-lysine. It possessed a great affinity for copper and rapidly formed the complex GHK-Cu. After further investigation, this activity was identified. It was suggested that GHK-Cu when combined with copper 2+, might operate as a complex [1].

It has been demonstrated by Pickart and colleagues that GHK-Cu has the ability to hasten the process of wound healing and contractions, enhance the absorption of skin that has been transplanted, and also exhibit anti-inflammatory properties [2]. Since then, it has been utilized in a wide variety of products for the benefit of the skin and hair. Furthermore, it has been demonstrated that GHK-Cu is able to: 

• In addition to repairing protective skin barrier proteins, tightening loose skin and reversing the thinning of aging skin in the process.

• Enhance the firmness, elasticity, and clarity of the skin - Decrease the appearance of fine lines and wrinkles, as well as improve the structure of the skin that has aged.

• Smooth rough skin and decrease the appearance of skin lesions, patchy hyperpigmentation, and pigmentation of the skin.

• Enhance the overall appearance of the skin.

• Reduce inflammation and damage caused by free radicals; promote the healing of wounds; shield skin cells from the harmful effects of ultraviolet radiation.

• Increase the rate of hair growth and thickness, as well as the size of the hair follicles [3].

GHK-Cu Peptide: Core Mechanisms of Action in Skin Regeneration

In addition to other techniques like titration, the molecular structure of the GHK copper complex (GHK-Cu) has been thoroughly investigated utilizing crystallography using EPR spectroscopy, X-ray absorption spectroscopy, and PMR spectroscopy. Nitrogen found in the imidazole neighboring chain of the histidine, additional nitrogen from the alphanumeric amino group of glycine, and the processed amide nitrogen of a glycine-histidine peptide link coordinate the Cu (II) ion within the GHK-Cu complex.

GHK-Cu seems to penetrate the stratum corneum, the horny layer of the skin, in enough amounts to initiate regenerating processes. As the pH rises, copper complexes' permeability coefficients rise as well. Only the tripeptide GHK and its copper-containing complexes, GHK-Cu and (GHK)(2)-Cu, have been shown to be able to move across the stratum corneum membrane model [36–38]. Zn-pectinate microparticles loaded with "glycyl-L-histidyl-L-lysine-Cu(II) (GHK-Cu(2+))" were created as "hydroxypropyl cellulose (HPC) compression-coated tablets" to deliver GHK to the colon.

The amount of medication and the concentration of the cross-linking agent had a significant impact on the dissolution of GHK-Cu(2+) via Zn-pectinate microparticles, but not the amount of surfactant. Within four hours, 50–80% of the drug dose was released by the microparticles. A colonic delivery system was demonstrated by the ideal microparticle composition (F8) coated with the comparatively hydrophobic polymer HPC.

This study suggests that GHK might be included in an internal delivery system. GHK ought to be able to be included in a dietary supplement that has no negative effects and numerous health-promoting qualities. In addition to the topical distribution, these formulations can be utilized to enhance skin healing.

Its capacity to form compounds with copper (II) is what makes GHK unique [51]. Since copper is necessary for over a dozen essential enzymes in human tissues and skin, including those involved in the development of connective tissue, antioxidant defense, and cellular respiration, this is extremely significant.

Additionally, copper has signaling properties and can affect metabolism and cell behavior. For instance, for stem cells to begin multiplying and mending tissues, there must be enough copper. Additionally, GHK lowers the amount of free ionic copper, reducing the risk of oxidative damage [4].

GHK-Cu Clinical Research: Evidence of Regenerative Properties

Studies conducted in vitro verified that administering GHK to lung fibroblasts corrected adverse alterations linked to a reduction in TGF-beta activity. It has been demonstrated that specific flaws in lung fibroblasts isolated from individuals with COPD hindered their capacity to contract and rebuild collagen gel.

Collagen gel contraction and remodeling were recovered when these fibroblasts received therapy with either GHK or TGF-beta, and they were able to match fibroblasts isolated from the lungs of ex-smokers without COPD. Lung fibroblasts from patients with COPD were able to transform collagen gelatin into fibrils following GHK therapy. Additionally, the production of integrin beta 1 was higher. These results suggest that by reviving the activity of genes implicated in the TGF-beta pathway, GHK may enhance tissue regeneration [5].

The ability of GHK to heal wounds has been demonstrated in numerous animal experiments. GHK seems to promote wound healing via a number of different pathways. GHK, either by itself or in conjunction with a high-dose helium-neon laser, enhanced granular tissue development and wound contraction in rabbit experimental wounds. It also increased the activity of the antioxidant enzymes and promoted blood vessel growth [6, 7].

In both diabetic and healthy rats, collagen dressings containing GHK (PIC-Peptide Incorporated Collagen) sped up wound healing. Higher levels of glutathione (GSH) and ascorbic acid, improved epithelialization, greater collagen synthesis, and activated mast cells and fibroblasts were all observed in the treated group's wounds.

PIC-treated wounds in healthy rats resulted in a nine-fold increase in collagen [8, 9]. In rats, GHK-Cu accelerated the healing of ischaemic open wounds. In comparison to vehicle-alone or untreated wounds, wounds showed faster healing and lower concentrations of metalloproteinases 2 and 9 in addition to TNF-β, a key inflammatory cytokine [10].

GHK-Cu Applications: Current Research and Clinical Uses

Animal studies verified GHK-Cu's ability to repair wounds. In rabbits, GHK-Cu enhanced blood vessel development, wound healing, and antioxidant enzyme levels. In rats, mice, and pigs, this chemical also caused systemic wound healing. By lowering TNF-alpha and promoting collagen synthesis, it helped rats' diabetic and ischaemic wounds heal more quickly. Additionally, it helped dogs' pad wounds heal [12–17]. GHK has been widely used in anti-aging cosmetic products due to its well-documented regeneration of skin activity [1].  GHK-Cu has recently gained attention as a potential treatment for skin inflammation, metastatic colon cancer, and chronic obstructive pulmonary disease (COPD). At least 4,000 genes in the genome of humans have been shown to be up and down-regulated by it, effectively restoring DNA to a more wholesome form [2].

These investigations provide fresh insight into the GHK-Cu peptide's role in skin remodeling. After 71 women with moderate to advanced evidence of photoaging had their facial skin treated with a GHK-Cu face cream for 12 weeks, the visual signs of aging decreased. The lotion boosted skin density and thickness, decreased fine lines and wrinkle depth, and enhanced skin flexibility, clarity, and appearance [11].

GHK-Cu Innovation: Future Research and Development Directions

GHK is a well-researched, safe, and reasonably priced substance that has numerous beneficial effects on various tissues and systems. For many years, it has been utilized extensively in human anti-aging and cosmetic goods with no negative side effects.

It is simple to include in creams, serums, liposomes, dermal patches, or microneedles. Since it isn't currently formed into dietary supplements, we believe that one potential avenue for future research is the development and testing of GHK-based formulations for internal use to promote the health of senior populations and as complementary therapies in the treatment of cancer.

GHK also has the ability to be turned into an anti-pain and anti-anxiety supplemental medicine, and it may be a crucial part of a future complicated approach to COPD therapy, according to both biology and gene evidence [3].

References

1. Pickart, L., The human tri-peptide GHK and tissue remodeling. Journal of Biomaterials Science, Polymer Edition, 2008. 19(8): p. 969-988.

2. Pickart, L., J.M. Vasquez-Soltero, and A. Margolina, GHK and DNA: resetting the human genome to health. BioMed research international, 2014. 2014(1): p. 151479.

3. Pickart, L. and A. Margolina, Regenerative and protective actions of the GHK-Cu peptide in the light of the new gene data. International journal of molecular sciences, 2018. 19(7): p. 1987.

4. Pickart, L., J.M. Vasquez-Soltero, and A. Margolina, GHK peptide as a natural modulator of multiple cellular pathways in skin regeneration. BioMed research international, 2015. 2015(1): p. 648108.

5. Campbell, J.D., et al., A gene expression signature of emphysema-related lung destruction and its reversal by the tripeptide GHK. Genome medicine, 2012. 4: p. 1-16.

6. Cangul, I.T., et al., Evaluation of the effects of topical tripeptide‐copper complex and zinc oxide on open‐wound healing in rabbits. Veterinary dermatology, 2006. 17(6): p. 417-423.

7. Gul, N.Y., et al., The effects of topical tripeptide copper complex and helium‐neon laser on wound healing in rabbits. Veterinary Dermatology, 2008. 19(1): p. 7-14.

8. Arul, V., et al., Biotinylated GHK peptide incorporated collagenous matrix: A novel biomaterial for dermal wound healing in rats. Journal of Biomedical Materials Research Part B: Applied Biomaterials: An Official Journal of The Society for Biomaterials, The Japanese Society for Biomaterials, and The Australian Society for Biomaterials and the Korean Society for Biomaterials, 2005. 73(2): p. 383-391.

9. Arul, V., R. Kartha, and R. Jayakumar, A therapeutic approach for diabetic wound healing using biotinylated GHK incorporated collagen matrices. Life sciences, 2007. 80(4): p. 275-284.

10. Canapp Jr, S.O., et al., The effect of topical tripeptide‐copper complex on healing of ischemic open wounds. Veterinary Surgery, 2003. 32(6): p. 515-523.

11. Leyden, J., et al. Skin care benefits of copper peptide containing facial cream. in American Academy of Dermatology 60th Annual Meeting. 2002. American Academy of Dermatology.