include carrier peptides, signal peptides, and neurotransmitter peptides.25 Carrier peptides are designed to bind to another ingredient and facilitate transportation of the agent to the active site.26 An example of a carrier peptide is GHK-Cu (Glycyl-Lhistidyl- L-lysine Copper), which was designed to deliver copper, a trace element necessary for healing, into wounds.27 This peptide, composed of glycine, histidyl, and lysine, was isolated from human plasma and then synthetically engineered for use in cosmeceuticals designed to minimize the appearance of fine lines and wrinkles in conjunction with the moisturizing vehicle. Signal peptides are intended to increase collagen, elastin, fibronectin, proteoglycan, and glycosaminoglycan production.28 The most popular signal peptide is palmitoyl pentapeptide, abbreviated Pal-KTTKS, composed of lysine, threonine, threonine, lysine, and serine. It is a procollagen I fragment that demonstrated in vitro to stimulate the production of collagen I, III, and IV.29 Procollagen I fragments are intended to act as a signal down-regulating the production of collagenase. Other signal peptides include the hexapeptide VGVAPG, composed of valine, glycine, valine, alanine, proline, and glycine, which is thought to attach to receptors in the membrane of the fibroblast stimulating the synthesis of collagen, but decreasing the synthesis of elastin.30 Neurotransmitter peptides are intended to inhibit the release of acetylcholine at the neuromuscular junction and mimic botulinum toxin by selectively modulating SNAP-25. Acetyl hexapeptide-3 mimics the N-terminal end of the SNAP-25 protein inhibiting SNARE complex formation, thereby inducing muscle relaxation and minimization of wrinkles.31
Another mechanism for inducing activation and regeneration is the use of growth factors (GFs) and cytokines. The most commonly used growth factors in cosmeceuticals are transforming growth factor β1 (TGF-β1) inducing keratinocyte migration, epidermal growth factor (EGF) inducing epidermal proliferation, platelet derived growth factor (PDGF) inducing macrophage activation and matrix production, and fibroblast growth factor (FGF) such as the activity of the secretion of Cryptomphalus aspersa (SCA), which induces fibroblast proliferation and migration showing skin regenerative properties.32 The challenge with topical applied growth factors is their large molecular weight inhibiting skin penetration. Hydrophilic molecules larger than 500 daltons have very low skin penetration and thus remain inactive on the skin surface. Growth factors typically are in the range of 15,000 daltons and thus they must be penetration enhanced for skin delivery.33 Also, it seems that a small fraction of topically applied GFs penetrating into superficial epidermis, can elicit a fibroblastmediated response in the dermis and signaling molecules may pass through skin structures.34
Dermal stimulation can also be achieved through the use of stem cells, either of plant or animal origin, which are pluripotential cells capable of indefinite propagation in an undifferentiated state. Stem cells are present in the skin in the bulge region of the hair follicle, the interfollicular epidermis, and the sebaceous gland. Live stem cells cannot survive in a cosmeceutical at room temperature in a preservative laden formulation, thus ingredients that are stem derivatives are incorporated skin care products. An example of such an ingredient is Crytomphalus aspersa snail egg extract. This ingredient in vitro improved stem cell migration and differentiation, promoted extracellular matrix formation, improved cell adhesion, and stimulated the migration of epidermal keratinocytes and dermal fibroblasts.35
The last major concept in activation and regeneration is the modulation of circadian rhythms, based on fluctuations related to the day/night cycle, hormones, meals, sleep/wake cycle, adrenal gland production, thyroid gland, and clock genes.36 The human circadian clock is in the suprachiasmatic nucleus, located in the hypothalamus, with information transmitted via the retina that contains specialized photosensitive ganglion cells. Circadian rhythms are important in keratinocytes, fibroblasts, melanocytes, mast cells, and hair follicles.37 Skin functions affected by circadian rhythms include free radical production and neutralization, DNA damage and repair, keratinocyte/ fibroblast differentiation and proliferation, and barrier and immune functioning.38 During the day, the skin has the highest pH, sebum production, and thickness with the lowest cell proliferation. However, at night, the skin has the highest DNA repair, cell proliferation, barrier permeability, skin penetration, and blood flow. This has led to a new concept in skin care based
Another mechanism for inducing activation and regeneration is the use of growth factors (GFs) and cytokines. The most commonly used growth factors in cosmeceuticals are transforming growth factor β1 (TGF-β1) inducing keratinocyte migration, epidermal growth factor (EGF) inducing epidermal proliferation, platelet derived growth factor (PDGF) inducing macrophage activation and matrix production, and fibroblast growth factor (FGF) such as the activity of the secretion of Cryptomphalus aspersa (SCA), which induces fibroblast proliferation and migration showing skin regenerative properties.32 The challenge with topical applied growth factors is their large molecular weight inhibiting skin penetration. Hydrophilic molecules larger than 500 daltons have very low skin penetration and thus remain inactive on the skin surface. Growth factors typically are in the range of 15,000 daltons and thus they must be penetration enhanced for skin delivery.33 Also, it seems that a small fraction of topically applied GFs penetrating into superficial epidermis, can elicit a fibroblastmediated response in the dermis and signaling molecules may pass through skin structures.34
Dermal stimulation can also be achieved through the use of stem cells, either of plant or animal origin, which are pluripotential cells capable of indefinite propagation in an undifferentiated state. Stem cells are present in the skin in the bulge region of the hair follicle, the interfollicular epidermis, and the sebaceous gland. Live stem cells cannot survive in a cosmeceutical at room temperature in a preservative laden formulation, thus ingredients that are stem derivatives are incorporated skin care products. An example of such an ingredient is Crytomphalus aspersa snail egg extract. This ingredient in vitro improved stem cell migration and differentiation, promoted extracellular matrix formation, improved cell adhesion, and stimulated the migration of epidermal keratinocytes and dermal fibroblasts.35
The last major concept in activation and regeneration is the modulation of circadian rhythms, based on fluctuations related to the day/night cycle, hormones, meals, sleep/wake cycle, adrenal gland production, thyroid gland, and clock genes.36 The human circadian clock is in the suprachiasmatic nucleus, located in the hypothalamus, with information transmitted via the retina that contains specialized photosensitive ganglion cells. Circadian rhythms are important in keratinocytes, fibroblasts, melanocytes, mast cells, and hair follicles.37 Skin functions affected by circadian rhythms include free radical production and neutralization, DNA damage and repair, keratinocyte/ fibroblast differentiation and proliferation, and barrier and immune functioning.38 During the day, the skin has the highest pH, sebum production, and thickness with the lowest cell proliferation. However, at night, the skin has the highest DNA repair, cell proliferation, barrier permeability, skin penetration, and blood flow. This has led to a new concept in skin care based
