N-Prolyl Palmitoyl Tripeptide-56 Acetate (PP-56)

3D structure of PP-56

Extracellular Matrix plays an important role in maintaining the dermal architecture, cellular maintenance as well as in facilitating the signaling between the cells and between the environment and cells. The quality of the extracellular matrix impacts skin health via the synthesis of collagen, elastin, and many other molecules in the skin layers as its the medium for all the communications to occur. Studies have shown that when the matrix itself is old and the skin cells are younger, the skin cells did not function as expected. 1 On the contrary, When the matrix is young and the skin cells are old, the cells were able to function as expected.

The quality of the extracellular matrix is declined either due to stressors or with age there is a decline in the collagen levels and vice versa. Production of several collagens, fibronectin (Collagen I, Collagen III, Collagen IV) is well known to be modified with age and photo-exposures; consequently, this weakens the quality of dermal ECM.2 In addition, the impairment of collagen-VI induces a thinner dermis because of loosening property as an ECM organizer, a reduced production of collagen and proteoglycans, and deposition of fibronectin. So, improving the quality of the ECM and the production of its proteins is of interest to fight against skin ageing and damage.

The critical role exhibited by the extracellular matrix is due to the proteins present in it. These are referred to as matrikinin proteins. These proteins are produced by a set of genes called FOXO genes that are known as longevity genes because of their ability to coordinate cellular energy processes, synthesize natural antioxidants called sestrins, stimulate the synthesis of Collagen I and regulate many other processes that delay ageing.3

Collagen-I and some enzymes involved in its production were promoted at gene and protein levels. In addition, other proteins of the ECM such as fibronectin, collagen-IV, and collagen-VI were also increased whereas PP56 up-regulated genes of the FOXO–sestrin pathway. 3 N-Prolyl Palmitoyl Tripeptide-56 Acetate is a matrikinine like a peptide. It has been proven to upregulate the FOXO gene resulting in synthesis of Sestrins. Studies have also demonstrated that this peptide was able to synthesize many important proteins present in the ECM as well as Collagen I, Collagen IV, Collagen V, and fibronectin. The peptide significantly enhanced the production of collagen-I, collagen-III, and collagen-VI (+42%, +58%, and +113%, respectively. An increase in the production of enzymes involved in the protection, production, and maturation of collagen fibres was also observed.

Figure: 1 Effect of PP-56 on Collagen I production by Fibroblasts. Left panel shows collagen network and densification in untreated cells. Right panel shows collagen network and densification in PP-56 treated cells. PP-56 stimulates the production of more and dense Collagen I in fibroblasts.4

Figure 2: Upper panel represents untreated cells showing actin filaments ( green) and cofilin filaments ( orange ) of the ECM. The lower panel represents PP-56 treated cells showing actin and cofilin filaments. There is more production of both actin and cofilin in PP-56 treated cells.4

References:

  1. Collagen fragmentation promotes oxidative stress and elevates matrix metalliproteinase-1 in fibroblasts in ages human Am. J. Pathol. 174, 101–114, 2009.
  2. Decreases collagen production in chronologically aged skin: roles of age dependent alteration in fibroblast function and defective mechanical Am J.Pathol. 168, 1861–1868, 2006.
  3. Genetic association of FOXO1A and FOXO3A with longevity trait in Han Chinese populations. Hum. Molec. Genet. 18, 4897-4904.
  4. A new matrikine-derived peptide up-regulates longevity genes for improving extracellular matrix architecture and connections of dermal cell with its matrix. International journal of Cosmetic Science, 2020, 42, 53-59.
  5. Patent WO 2016/097965.