The GHK sequence, known to play a pivotal role in stimulating fibroblasts, was initially identified in the plasma of multiple species in 1973 by Pickart et al.(1) Leveraging its dual characteristics, Pal-GHK appears to hold promise in the domain of skin research, contributing to advancements in skincare formulations and emphasizing its potential in the fortification of the extracellular matrix. Further exploration into its mechanism of action and its effects on long-term skin health remains a focal point of ongoing scientific investigation.
The mechanism of Palmitoyl-GHK involves its hypothesized ability to stimulate collagen production, a vital constituent of the skin’s extracellular matrix. This property is speculated to be attributed to the presence of the Gly-His-Lys sequence, which represents a fragment of collagen released during the process of collagen hydrolysis, characteristic of wound healing and inflammatory responses.
Consequently, the tripeptide is believed to serve as a natural signaling molecule to fibroblasts, the primary cellular agent responsible for synthesizing collagen and other critical components of the extracellular matrix.(1) Given collagen’s indispensable role in providing structural integrity and support to the skin, Pal-GHK peptide may hold potential to contribute to the enhancement of skin firmness and texture.
Furthermore, Palmitoyl-GHK appears to exhibit potential antioxidant attributes, offering defense against the detrimental impacts of free radicals. These unstable molecules are recognized for their ability to damage cellular structures, thereby contributing to visual indications of age-related physiological decline. By potentially mitigating the impact of free radicals, Pal-GHK peptide may reduce cellular aging processes and counteract inflammation within the skin.
Research and Scientific Studies
Pal-GHK peptide has garnered significant attention in diverse research studies owing to its potential multifaceted applications in the realm of skin biology research.
As a synthetic peptide incorporating a palmitoyl moiety and the tripeptide sequence Gly-His-Lys, it has indicated potential in stimulating collagen production, possibly enhancing skin elasticity and texture. Its probable involvement in promoting wound healing and fortifying the extracellular matrix has led to its exploration in various formulations to improve skin health and mitigate the effects of age-related decline.
Pal-GHK Peptide and Collagen Synthesis
Research conducted by Maquart et al. in 1988, as documented in the journal FEBS Letters, unveiled the potential underpinning the action of Gly-His-Lys in Pal-GHK.
This tripeptide sequence emerges as a byproduct during the hydrolysis of collagen, indicative of collagen degradation. Such fragments generated during tissue damage may serve as signaling molecules to activate fibroblasts, thereby initiating the synthesis of new collagen. Pal-GHK, with its analogous Gly-His-Lys sequence, presents a plausible capacity to stimulate the production of collagen, elastin, and glycosaminoglycans, pivotal constituents of the skin’s extracellular matrix.
The researchers postulated that the presence of the GHK triplet in the alpha 2(I) chain of type I collagen implies potential liberation by proteases at wound sites, with in situ healing effects.
A placebo-controlled clinical study, involving 23 research subjects, provides additional empirical data of Pal-GHK’s potential to stimulate collagen synthesis. Skin thickness was used as a metric, and the results indicated a modest yet statistically significant increase of approximately 4% compared to the placebo, supporting the researcher’s hypothesis about the peptide’s impact in skin regeneration.(2)
Pal-GHK Peptide and Anti-Oxidative Potential
In a laboratory experiment conducted by Sakuma et al. in 2018, intriguing findings suggested that the amino-acid sequence within Pal-GHK possesses notable antioxidative potential.(3)
This potential appeared to surpass the efficacy of other widely recognized antioxidative peptides, including carnosine and reduced glutathione, frequently employed in applicable research. The researchers further expounded that, through experiments employing an ESR spin-trapping technique, Pal-GHK might diminish signals associated with hydroxyl (·OH) and peroxyl (ROO·) radicals generated in distinct chemical reaction systems.
Active radicals, such as reactive oxygen species (ROS), reactive nitrogen species (RNS), and reactive carbonyl species (RCS), are considered to play crucial roles in mediating photodamage and inflicting harm upon lipids, DNA, and proteins. Studies have intimated that the amino acid sequence embedded in Pal-GHK may harbor the capacity to deter protein glycation and manifest anti-RCS attributes against various radicals, including acrolein, malondialdehyde, and 4-hydroxynoneal.(4)
Additionally, Pal-GHK has emerged as a potential regulator of iron release from ferritin, an enzyme that catalyzes lipid peroxidation. One study reported a remarkable 87% reduction in iron release from damaged tissue following exposure to Pal-GHK, exhibiting mitigating oxidation within the affected tissues.(5)
Furthermore, Pal-GHK appears to offer promise in diminishing the production of reactive oxygen species and inflammatory cytokines, while concurrently enhancing the activity of antioxidant enzymes. In an animal trial, Pal-GHK exhibited some capacity to suppress the activation of the NF-κB and p38 MAPK signaling pathways, both closely associated with inflammation. Consequently, this appeared to lead to reduced infiltration of inflammatory cells in the lungs of mice with lung damage, alongside lower levels of TNF-1 and IL-6 production.(6)
Additionally, it has been proposed that Pal-GHK holds potential in ameliorating oxidative stress triggered by smoke inhalation. Research suggests that the amino-acid sequence present in Pal-GHK may mitigate oxidative stress in alveolar epithelial cells by elevating the expression of Nrf2 (Nuclear factor erythroid 2-related factor 2) and concomitantly reducing reactive oxygen species levels in cell cultures. Nrf2 is a regulatory protein implicated in governing the expression of antioxidant proteins, serving as a protective shield against oxidative damage arising from injury and inflammation.(7)
Pal-GHK Peptide and Wrinkle Control
A clinical trial was undertaken to evaluate the possible efficacy of Pal-GHK in diminishing wrinkle depth. The study, involving a cream formulation incorporating Pal-GHK, encompassed 15 participants, as reported by the researchers.(6) Notably, the trial period revealed a noticeable reduction in wrinkle length, depth, and skin roughness, indicating the peptide’s potential in mitigating the visible signs of aging.
Furthermore, an additional unrelated clinical investigation explored the combined effects of Pal-GHK tripeptide and Pal-GQPR, a palmitoylated tetrapeptide comprised of the sequence Pal-Gly-Gln-Pro-Arg, derived from immunoglobulin G (IgG). The study, conducted as a blind, randomized clinical trial with the participation of 28 subjects, observed significant improvements in wrinkle depth, volume, density, skin roughness, and the surface area occupied by deep wrinkles.(7) This comprehensive analysis underscores the synergistic impact of the combined peptides in possibly ameliorating various parameters associated with aging and skin texture.
In Summary
Pal-GHK peptide, a synthetic compound integrating a palmitoyl group and the tripeptide sequence Gly-His-Lys, has emerged as a promising entity. Its potential lies in stimulating collagen production and enhancing skin elasticity, with possible implications for wound healing and fortifying the extracellular matrix.
Studies underscore its anti-oxidative potential to counteract free radicals and mitigate oxidative stress. Additionally, clinical investigations have highlighted its probable efficacy in reducing wrinkle depth, length, and skin roughness, signifying its role in promoting skin rejuvenation and texture refinement.
With its multifaceted benefits, Pal-GHK continues to remain a focal point in the development of innovative skincare formulations and related research.
NOTE: These products are intended for laboratory research use only. This peptide is not intended for personal use. Please review and adhere to our Terms and Conditions before ordering.
References:
- Pickart, L., & Thaler, M. M. (1973). Tripeptide in human serum which prolongs survival of normal liver cells and stimulates growth in neoplastic liver. Nature: New biology, 243(124), 85–87. https://pubmed.ncbi.nlm.nih.gov/4349963/
- Lintner, K., & Peschard, O. (2000). Biologically active peptides: from a laboratory bench curiosity to a functional skin care product. International journal of cosmetic science, 22(3), 207–218. https://doi.org/10.1046/j.1467-2494.2000.00010.x
- Sakuma, S., Ishimura, M., Yuba, Y., Itoh, Y., & Fujimoto, Y. (2018). The peptide glycyl-ʟ-histidyl-ʟ-lysine is an endogenous antioxidant in living organisms, possibly by diminishing hydroxyl and peroxyl radicals. International journal of physiology, pathophysiology and pharmacology, 10(3), 132–138.
- Cebrián, J., Messeguer, A., Facino, R. M., & García Antón, J. M. (2005). New anti-RNS and -RCS products for cosmetic treatment. International journal of cosmetic science, 27(5), 271–278. https://doi.org/10.1111/j.1467-2494.2005.00279.x
- Park, J. R., Lee, H., Kim, S. I., & Yang, S. R. (2016). The tri-peptide GHK-Cu complex ameliorates lipopolysaccharide-induced acute lung injury in mice. Oncotarget, 7(36), 58405–58417. https://doi.org/10.18632/oncotarget.11168
- Sakuma, S., Ishimura, M., Yuba, Y., Itoh, Y., & Fujimoto, Y. (2018). The peptide glycyl-ʟ-histidyl-ʟ-lysine is an endogenous antioxidant in living organisms, possibly by diminishing hydroxyl and peroxyl radicals. International journal of physiology, pathophysiology and pharmacology, 10(3), 132–138.
- Zhang, Q., Yan, L., Lu, J., & Zhou, X. (2022). Glycyl-L-histidyl-L-lysine-Cu2+ attenuates cigarette smoke-induced pulmonary emphysema and inflammation by reducing oxidative stress pathway. Frontiers in molecular biosciences, 9, 925700. https://doi.org/10.3389/fmolb.2022.925700