GHK-Cu: A Multi-Functional Peptide

Research Example #1: Regenerative and Protective Actions

The human peptide GHK-Cu (glycyl-l-histidyl-l-lysine) exhibits multiple biological actions that appear to be health-positive. GHK-Cu stimulates blood vessel and nerve outgrowth, increases collagen, elastin, and glycosaminoglycan synthesis, and supports dermal fibroblast function. It has demonstrated tissue repair capabilities for skin, lung connective tissue, bone tissue, liver, and stomach lining. GHK-Cu also possesses powerful cell-protective actions, including anti-cancer and anti-inflammatory activities, lung protection, restoration of COPD fibroblasts, suppression of aging-related molecules like NFκB, and activities such as anti-anxiety, anti-pain, and anti-aggression. Additionally, GHK-Cu promotes DNA repair and activates cell cleansing via the proteasome system. Recent genetic data reveal that GHK-Cu regulates multiple biochemical pathways, explaining its diverse protective and healing actions.

Research Example #2: Skin Regeneration

GHK-Cu is present in human plasma, saliva, and urine but declines with age. It functions as a complex with copper 2+, accelerating wound healing and skin repair. GHK-Cu stimulates the synthesis and breakdown of collagen and glycosaminoglycans and modulates the activity of metalloproteinases and their inhibitors. It also restores replicative vitality to fibroblasts after radiation therapy and attracts immune and endothelial cells to injury sites. GHK-Cu promotes wound healing in skin, hair follicles, the gastrointestinal tract, bone tissue, and foot pads of dogs, and induces systemic wound healing in rats, mice, and pigs. In cosmetic products, GHK-Cu tightens loose skin, improves elasticity, skin density, and firmness, reduces fine lines and wrinkles, photodamage, and hyperpigmentation, and increases keratinocyte proliferation. GHK-Cu is proposed as a therapeutic agent for skin inflammation, COPD, and metastatic colon cancer. It can up- and downregulate at least 4,000 human genes, essentially resetting DNA to a healthier state.

Research Example #3: Preventing Oxidative Stress

GHK-Cu is a naturally occurring plasma peptide that significantly declines during aging. It improves wound healing, tissue regeneration, and stimulates collagen and decorin production. GHK-Cu supports angiogenesis and nerve outgrowth, improves aging skin and hair condition, and possesses antioxidant and anti-inflammatory effects. Additionally, it increases cellular stemness and trophic factor secretion by mesenchymal stem cells. GHK-Cu‘s antioxidant actions include blocking reactive oxygen and carbonyl species formation, detoxifying lipid peroxidation products like acrolein, protecting keratinocytes from lethal UVB radiation, and blocking hepatic damage by dichloromethane radicals. Recent studies show that GHK-Cu can switch gene expression from a diseased to a healthier state for certain cancers and COPD. The Broad Institute’s Connectivity Map indicates that GHK-Cu induces a 50% or greater change in the expression of 31.2% of human genes, highlighting its significant biological impact.

Thymosin Beta-4: A Promising Hair Growth Peptide

Research Example #1: Role in Hair Growth

Thymosin Beta-4 (Tβ4) is known to play a role in hair growth, though its mechanism is unclear. Studies using Tβ4 epidermal-specific over-expressing and global knockout mouse models have explored how Tβ4 affects hair growth. Depilation and histological examination confirmed Tβ4‘s effect on hair growth, hair shaft number, and hair follicle structure. Changes in the expression of β-catenin and Lef-1, key molecules in the Wnt signaling pathway, paralleled changes in Tβ4 expression. Tβ4 over-expressing mice showed increased mRNA and protein expression of MMP-2 and VEGF, while knockout mice showed decreased expression. Tβ4 appears to regulate VEGF and MMP-2 via the Wnt/β-catenin/Lef-1 signaling pathway, influencing blood vessel growth around hair follicles and activating cell migration. Tβ4 may have potential for treating hair growth problems in adults, warranting further studies.

Research Example #2: Activation of Hair Follicle Stem Cells

Thymosin Beta-4, a 43-amino acid polypeptide, promotes angiogenesis and wound healing. It stimulates hair growth in normal rats and mice, with specific hair follicular keratinocytes expressing Tβ4 during the hair growth cycle. These keratinocytes, originating from the hair follicle bulge region (a skin stem cell niche), show increased migration and differentiation in the presence of Tβ4Tβ4 increases the expression and secretion of matrix metalloproteinase-2, aiding hair growth by promoting stem cell migration and differentiation, and extracellular matrix remodeling.

Research Example #3: Hair Growth Induction in Mice

To study Tβ4‘s role in hair growth and hair follicle development, researchers generated Tβ4 overexpressing and knockout mice. Depilation experiments showed faster hair regrowth in Tβ4-overexpressing mice and slower regrowth in knockout mice. Histological analysis revealed more hair shafts and clustered hair follicles in Tβ4-overexpressing mice, while knockout mice had fewer hair shafts. Increased Tβ4 expression at mRNA and protein levels was confirmed in Tβ4-overexpressing mice, along with increased VEGF expression. Mechanistically, Tβ4-overexpressing mice showed increased protein expression and phosphorylation of P38, ERK, and AKT, while knockout mice had decreased levels. Tβ4 appears to regulate P38/ERK/AKT signaling via VEGF expression, affecting hair growth speed, hair follicle pattern, and hair shaft number.

Overall Conclusion

GHK-Cu works through a multi-modal approach, accelerating wound healing in skin, hair follicles, the gastrointestinal tract, bone tissue, and foot pads of dogs. It also induces systemic wound healing in rats, mice, and pigs. In cosmetic products, GHK-Cu tightens loose skin, improves elasticity, skin density, and firmness, reduces fine lines and wrinkles, photodamage, and hyperpigmentation, and increases keratinocyte proliferation. GHK-Cu has therapeutic potential for skin inflammation, COPD, and metastatic colon cancer, and can regulate at least 4,000 human genes, essentially resetting DNA to a healthier state.

Thymosin Beta-4 (Tβ4) stimulates VEGF expression, activating downstream signaling pathways via MAPK/P38, MAPK/ERK, and PI3K/AKT. These studies establish the basis for further exploration of Tβ4‘s function and molecular mechanisms in hair growth. Researchers have identified the significant role of GHK-Cu and Thymosin Beta-4 in hair growth, with experiments demonstrating that GHK-Cu and Tβ4 overexpression promotes hair growth, while the loss of these peptides suppresses it.

In conclusion, both GHK-Cu and Thymosin Beta-4 show great promise in promoting hair growth and improving overall hair health. Ongoing research is crucial to further understand their mechanisms and optimize their therapeutic potential for treating hair loss.

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