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▎GHK - Cu Overview
GHK-Cu, a naturally occurring tripeptide copper complex, possesses multiple biological activities. It exerts antioxidant, anti-inflammatory, and collagen synthesis-promoting effects by regulating copper ion metabolism, being widely applied in cosmetic skincare, anti-aging, and healthcare fields. In cosmetic skincare, GHK-Cu can improve skin aging, promote wound healing, enhance skin elasticity, while also possessing anti-inflammatory and antioxidant functions. Additionally, it is used to promote hair health, regulate gene expression, and assist in treating certain diseases. As a multifunctional bioactive molecule, GHK-Cu demonstrates significant potential in delaying aging, improving skin health, and enhancing tissue repair capabilities.
▎GHK - Cu Structure
Source: PubChem | Sequence: Gly-His-Lys Molecular Formula: C28H46CuN12O8 Molecular Weight: 742.3g/mol CAS Number: 130120-56-8 PubChem CID: 9831891 Synonyms: Bisprezatide copper;DL1TR6W6VM |
▎GHK - Cu Research
What is the research background of GHK-Cu?
Research Progress of Active Peptides:
Since the 20th century, the research on bioactive peptides in the field of life sciences has been continuously deepened. Scientists have gradually realized that peptides play a crucial role in living organisms. They are not only components of proteins but also have independent biological functions and participate in regulating various physiological processes of organisms, such as cell growth, differentiation, and immunomodulation. This in-depth understanding of peptides provides a theoretical basis and research direction for the discovery and study of GHK-Cu.
Exploration of Plasma Components:
In the detailed study of human plasma components, scientists are committed to analyzing the composition and functions of various biomolecules in plasma. As an important body fluid in the human body, plasma contains a variety of proteins, peptides, hormones, electrolytes, and other substances, and it is a key medium for maintaining the normal physiological functions of the human body. In the 1970s, researchers accidentally discovered a special tripeptide during the analysis of plasma proteins. Its amino acid sequence is glycyl-histidyl-lysine, namely GHK. This discovery aroused great interest among scientists and prompted them to further explore the role and characteristics of this tripeptide in plasma.
Biological Significance of Copper Ions:
At the same time, the important role of copper ions in biology has gradually attracted attention. Copper is one of the essential trace elements in the human body and participates in many biochemical reactions. It is a component or activator of many key enzymes and plays an indispensable role in maintaining the normal metabolism of cells, respiration, and the synthesis of collagen. During the study of the biological functions of copper ions, scientists found that copper ions can bind to certain peptide substances to form complexes with special biological activities. This discovery provides an important clue for the study of the binding of GHK and copper ions and their potential functions.
Promotion of Aging-related Research:
With the development of society and the increasingly prominent problem of population aging, aging-related research has become an important topic in the field of life sciences. Scientists are trying to find biomarkers and regulatory factors closely related to the aging process to reveal the mechanism of aging and explore methods to delay aging. In this context, it has been found that the concentration of GHK-Cu in the human body gradually decreases with age, which implies that GHK-Cu may have some connection with the aging process. This discovery further stimulates researchers to conduct in-depth studies on the source, function, and application of GHK-Cu in the field of anti-aging, and promotes the continuous development of related research.
What is the mechanism of action of GHK-Cu?
Promoting Tissue Repair and Regeneration:
Stimulating Blood Vessel and Nerve Growth:
Existing studies have shown that GHK-Cu can stimulate the growth of blood vessels and nerves. It may achieve this effect by regulating specific growth factors and signaling pathways. For example, it may promote the expression of vascular endothelial growth factor (VEGF), thereby stimulating angiogenesis[1]. In terms of nerve growth, it may promote the survival, proliferation, and axonal growth of nerve cells by influencing signaling molecules related to nerve growth.
Increasing the Synthesis of Collagen, Elastin, and Glycosaminoglycans:
GHK-Cu can increase the synthesis of collagen, elastin, and glycosaminoglycans. Collagen is an important component of tissues such as the skin and bones, elastin gives tissues elasticity, and glycosaminoglycans play an important role in maintaining the moisture and elasticity of tissues. The specific mechanism may involve regulating the expression of related genes and signaling pathways, such as activating specific transcription factors in fibroblasts to promote the expression of genes related to collagen synthesis[1].
Supporting the Function of Dermal Fibroblasts:
Dermal fibroblasts play a key role in maintaining the structure and function of the skin. GHK-Cu can support the function of dermal fibroblasts, including promoting cell proliferation, migration, and the synthesis of extracellular matrix components. This may be achieved by regulating the signaling pathways and gene expression within fibroblasts.
Cell Protective Effects:
Anticancer Activity:
GHK-Cu has multiple anticancer activities. It may exert anticancer effects by inhibiting the proliferation of cancer cells, inducing apoptosis of cancer cells, and suppressing the invasion and metastasis of cancer cells. The specific mechanism may involve regulating the cell cycle, activating the apoptosis signaling pathway, and inhibiting tumor-related signaling pathways [1].
Anti-inflammatory Effect:
GHK-Cu has a powerful anti-inflammatory effect. It can inhibit the production of inflammatory factors such as tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6), and at the same time increase the activity of antioxidant enzymes such as superoxide dismutase (SOD). Its anti-inflammatory mechanism may be related to the inhibition of the NF-κB p65 and p38 MAPK signaling pathways, thereby reducing the inflammatory response[2].
Lung Protection and Repair of Chronic Obstructive Pulmonary Disease (COPD):
GHK-Cu has a protective and reparative effect on lung tissue. It can inhibit the inflammatory response in lung tissue, reduce the damage and fibrosis of lung tissue. For lung fibroblasts of patients with chronic obstructive pulmonary disease (COPD), GHK-Cu can restore their function, possibly by regulating related signaling pathways and gene expression[1].
Anxiolytic, Analgesic, and Anti-aggression Effects:
GHK-Cu also has anxiolytic, analgesic, and anti-aggression effects, but the specific mechanisms are not yet fully understood. It may be related to the regulation of signaling pathways and neurotransmitters in the nervous system.
DNA Repair and Cell Cleaning:
DNA Repair:
GHK-Cu has the function of DNA repair. It may repair damaged DNA by activating specific DNA repair enzymes or signaling pathways. This is of great significance for maintaining the normal function of cells and preventing the occurrence of diseases such as aging and cancer [1].
Activating Cell Cleaning (through the Proteasome System):
GHK-Cu can activate the proteasome system of cells, promoting the degradation and clearance of intracellular proteins. This helps to maintain the stability of the intracellular environment and prevent protein aggregation and cell dysfunction[1].
Hypothesis on the Mechanism of Acupuncture: Some studies have proposed the hypothesis that the mechanism of action of acupuncture may be achieved through GHK-Cu. Although the specific mechanism remains to be further studied, this provides a new perspective for understanding the mechanism of action of GHK-Cu[3].
The plasma level and clinical relevance of GHK in patients with silicosis: A. Plasma GHK levels in healthy subjects and patients with silicosis. B. Plasma GHK levels in patients with silicosis in different clinical stages of the disease. C. Lung imaging manifestations and plasma GHK levels in a healthy control population and in patients in different clinical stages of silicosis. D. Correlation between the plasma GHK levels and FEV1%pre in patients with silicosis. E. Correlation between the plasma GHK levels and the DLCO%pre in patients with silicosis.
Source:PubMed[6]
What are the applications of GHK-Cu?
Skin Repair and Beauty:
Stimulating Collagen Synthesis:
GHK-Cu can stimulate the synthesis of collagen, elastin, and glycosaminoglycans. Collagen is an important component of the skin, which gives the skin elasticity and firmness[1]. With the increase of age, the synthesis of collagen gradually decreases, leading to skin relaxation and the appearance of wrinkles. By promoting the production of collagen, GHK-Cu can improve the elasticity and firmness of the skin and reduce the formation of wrinkles.
Promoting Blood Vessel and Nerve Growth:
It has the effect of stimulating the growth of blood vessels and nerves [1]. Good blood circulation is crucial for the health of the skin. It can provide sufficient nutrients and oxygen for skin cells and promote the metabolism of the skin. In addition, the growth of nerves also contributes to the sensory and responsive abilities of the skin.
Supporting the Function of Dermal Fibroblasts:
GHK-Cu supports the function of dermal fibroblasts. Fibroblasts are one of the main cell types in the skin, and they are responsible for synthesizing collagen, elastin, and other extracellular matrix components[1]. GHK-Cu can enhance the activity of fibroblasts and improve their ability to synthesize the extracellular matrix, thus helping to maintain the structure and function of the skin.
Wound Healing:
GHK-Cu shows significant effects in wound healing. Studies have shown that it can accelerate the wound healing process, promote the growth of granulation tissue, and the production and accumulation of collagen. In addition, GHK-Cu can regulate the transformation of macrophages from the M2 phase, effectively inhibit the expression of inflammatory factors TNF-α and IL-6 in tissues, release anti-inflammatory factors such as TGF-β and iNOS, accelerate the expression of the HIF-1α pathway, promote the expression of VEGF to achieve the effect of promoting angiogenesis, and accelerate tissue repair.
Anti-aging:
GHK-Cu has multiple anti-aging effects. It can inhibit the activity of molecules such as NFκB, which are considered to accelerate the aging process (Pickart L, 2018). In addition, it also has anxiolytic, analgesic, and anti-aggression activities, DNA repair, and the function of activating cell cleaning through the proteasome system.
As a Cosmetic Ingredient:
Due to its effects on skin repair and anti-aging, GHK-Cu is widely used in cosmetics. For example, liposomes based on anionic (AL) and cationic (CL) hydrogenated lecithin can be used as a skin delivery system for GHK-Cu[4]. These liposomes are stable, have a small particle size (about 100nm), and a high bilayer fluidity, which can effectively deliver GHK-Cu into the skin. As a cosmetic ingredient, GHK-Cu can not only improve the appearance of the skin but also enhance the health of the skin.
Medical Field:
Treatment of Acute Lung Injury:
GHK-Cu has a protective effect on acute lung injury (ALI). In in vitro experiments on RAW 264.7 macrophages induced by lipopolysaccharide (LPS) and in a mouse model of acute lung injury in vivo, GHK-Cu treatment reduced the production of reactive oxygen species (ROS), increased the activity of superoxide dismutase (SOD), and at the same time reduced the production of TNF-α and IL-6, acting through the inhibition of the NF-κB p65 and p38 MAPK signaling pathways[2]. In addition, GHK-Cu can also reduce the pathological changes of lung tissue induced by LPS and inhibit the infiltration of inflammatory cells into the lung parenchyma.
Treatment of Pulmonary Fibrosis:
GHK-Cu has shown a therapeutic effect in a mouse model of pulmonary fibrosis induced by bleomycin (BLM)[5]. Idiopathic pulmonary fibrosis is a serious lung disease, and oxidative stress and inflammation are its key pathogenic mechanisms. GHK-Cu may play a protective role through antioxidant stress and anti-inflammatory pathways.
Treatment of Silicosis:
Silicosis is the most common type of pneumoconiosis, and there is currently no specific drug for its treatment. Studies have found that GHK-Cu has a therapeutic effect on silicosis. It can alleviate pulmonary inflammation and fibrosis in silicosis mice by targeting peroxiredoxin 6 (PRDX6), partly due to the inhibition of oxidative stress in alveolar macrophages induced by crystalline silica[6].
GHK-Cu has multiple functions and great significance. It can stimulate the synthesis of substances such as collagen, repair the skin, and delay aging, helping people pursue healthy and beautiful skin in the field of beauty and skin care. At the medical level, it provides a new direction for the treatment of lung diseases such as acute lung injury and pulmonary fibrosis, and is expected to improve the health of patients. Overall, GHK-Cu contributes to the development of life sciences, medicine, and the beauty industry, and has a positive impact on improving the quality of human life.
About The Author
The above-mentioned materials are all researched, edited and compiled by Cocer Peptides.
Scientific Journal Author
Bian Y is a researcher affiliated with multiple notable organizations. These include the State Key Lab Resp Hlth & Multimorbid, China-Japan Friendship Hospital, Chinese Academy of Medical Sciences - Peking Union Medical College, Natl Clin Res Ctr Resp Dis, Natl Ctr Resp Med, and Tongji University. His institutional affiliations reflect a broad background in medical and scientific research.
His research spans several important subject categories. He has expertise in the Respiratory System, Oncology, General & Internal Medicine, Research & Experimental Medicine, and Biochemistry & Molecular Biology. His work in these fields is significant for advancing medical science and improving healthcare. Bian Y is listed in the reference of citation [6].
▎Relevant Citations
[1] Pickart L, Margolina A. Regenerative and Protective Actions of the GHK-Cu Peptide in the Light of the New Gene Data[J]. International Journal of Molecular Sciences, 2018,19(7).DOI:10.3390/ijms19071987.
[2] Park J R, Lee H, Kim S, et al. The tri-peptide GHK-Cu complex ameliorates lipopolysaccharide-induced acute lung injury in mice[J]. Oncotarget, 2016,7(36):58405-58417.DOI:10.18632/oncotarget.11168.
[3] Molt O Ripoll J P, Cointry G. Hypothesis of the mechanism of action of acupuncture through GHK-Cu[J]. International Journal of Health Science, 2024. DOI:10.22533/at.ed.1594202415026
[4] Dymek M, Olechowska K, Hąc-Wydro K, et al. Liposomes as Carriers of GHK-Cu Tripeptide for Cosmetic Application[J]. Pharmaceutics, 2023,15(10).DOI:10.3390/pharmaceutics15102485.
[5] Ma W, Li M, Ma H, et al. Protective effects of GHK-Cu in bleomycin-induced pulmonary fibrosis via anti-oxidative stress and anti-inflammation pathways[J]. Life Sciences, 2020,241:117139.DOI:10.1016/j.lfs.2019.117139.
[6] Bian Y, Deng M, Liu J, et al. The glycyl-l-histidyl-l-lysine-Cu(2+) tripeptide complex attenuates lung inflammation and fibrosis in silicosis by targeting peroxiredoxin 6[J]. Redox Biology, 2024,75:103237.DOI:10.1016/j.redox.2024.103237.
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