Bm Regenerate Anti Ageing Serum Contains the Hero Ingredient Tasmannia Lanceolata (Mountain Pepper Berry)

Bm Regenerate anti ageing serum contains the hero ingredient Tasmannia lanceolata (Mountain Pepper Berry) to stimulate collagen production and repair barrier function for smooth flawless skin.

It has been reported that expression of basement membrane (BM) proteins such as collagen XVII, laminin and nidogen is modulated by epidermal keratinocytes. Therefore, peptide derivatives with stimulatory effects on BM protein expression were developed as anti-aging ingredients.

1. Collagen IV

Collagen IV is a prominent component of the basement membranes (BM) through which inter- and intramolecular interactions shape a supramolecular matrix that controls cell adhesion, migration and differentiation. In addition to its structural function, recent studies have shown that type IV collagen is also implicated in rare genetic diseases such as Alport’s and Goodpasture’s syndromes.

The BM-specific structure of collagen IV is comprised of six alpha chains which can be assembled as a hexamer, a dimer via head-to-head interaction or a trimer by formation of four -chains with one -chain (Fig. 1). Each of the three chain types has a characteristic triple helix structure consisting of repeating -glycine and -proline residues, which gives rise to an extraordinary tensile strength.

An essential feature of collagen IV is its ability to self-assemble, with the formation of a complex network through inter- and intramolecular cross-linking. This self-assembly process is mediated by the carboxy-terminal NC1 domains of the a-chains, which are resistant to the protease action of bacterial collagenase and can be isolated from the BMs.

The NC1 domains of the a-chains are recognized by the integrin receptors a1b1 and a2b1, with binding sites located within a specific region of the hexamer. The hexamer is stabilized through the formation of disulfide bridges and covalently linked through lysyl-hydroxylysine bonds between adjacent chains.

2. Laminin

Laminin is the major component of the basement membrane that provides a stable attachment for epithelial cells and ensures communication between the two skin compartments. The short arms of the protein are involved in architectural functions and the long ones link the heparan sulfate proteoglycan perlecan and the bridging molecule nidogen to the collagen IV polymers that form the basement membrane.

Both heparan sulfate chains (perlecan) and nidogen bind to the g1 domain of the laminin 2 chain. Nidogen also binds to the heparan sulfate glycoprotein hyaluronic acid and interacts with a number of other molecules that contribute to its bridging function. The aesthetic skin care interaction of nidogen with the g1 domain of laminin is crucial for a proper hemidesmosomal assembly.

During keratinocyte sheet grafting in vitro or in vivo, nidogen was found to be deposited at the keratinocyte-epidermal interface. A large fraction of this nidogen was bound to the heparan sulfate-containing component laminin-5 (a3b3g2). Interestingly, the deletion of the nidogen binding site on the g1 chain of laminin-5 did not severely affect nidogen binding but had an impact on other activities of the protein.

In control 3D-cocultures a bright staining for nidogen, BM laminin and type IV collagen was clearly observed in the BM zone. However, upon Lgf treatment, nidogen appeared to dissociate from the BM lamina densa and became loosely organised. This loose structure was also visible by ImEM and confocal laser scanning microscopy and was accompanied by a lack of a hemidesmosomal structure as indicated by the splaying of nidogen.

3. Nidogen

Nidogens (formerly entactins) are a family of sulfated monomeric glycoproteins that have been shown to promote BM assembly and epithelial cell attachment through high-affinity binding with the laminin g1 chain. They also contain binding sites for perlecan and collagen IV and can function as instant stabilizers in molecular interactions, facilitating rapid BM remodeling. Mice lacking nidogen-1 have no overt phenotype, indicating that compensatory activities of the other mammalian nidogen isoforms compensate for the missing nidogen activity (Nidogen, b).

Nido-2 has been shown to promote BM formation in human skin cells and in vivo in an in vitro model system by acting as an integrin inhibitor. It also contains high-affinity binding sites for both laminin g1 and perlecan, thereby linking the heparan sulfate proteoglycans to the basal lamina.

Its heparan sulfate domain allows it to bind perlecan with high affinity, forming a highly stable complex. This interaction provides an important heparan sulfate bridge to the underlying laminin g1 network and is essential for nidogen induced BM formation in vivo.

The functional integrity of the dermal-epidermal junction – comprising the BM, hemidesmosomes and a meshwork of DEJ proteins – is crucial for skin barrier function. It has been demonstrated that BM defects in mice are lethal at an early developmental stage or around birth and that they cause a wide range of structural alterations including epithelial dissociation from type I collagen fibrils, impaired basal adhesion structures and small blood vessels with thin leaky walls. Nidogen-deficient mice exhibit an overall complex BM defect which includes impaired heparan sulfate deposition, increased gaps between the laminin g1 and g2 domains of perlecan and reduced levels of collagen IV in hemidesmosomes.

4. Heparin Sulfate Proteoglycans

Heparin sulfate (HS) is one of the functional polysaccharides in glycosaminoglycans, a class of biologically active compounds that act as endogenous superhydrators and promote skin hydration and homeostasis. Heparin, along with chondroitin/dermatan sulfate, keratan sulfate and hyaluronan, is synthesized in the Golgi apparatus via linker oligosaccharides (iduronic acid, GlcA, and glucuronic acid, GlcNAc) attached to core proteins (including laminin, nidogen, and collagen IV). HS is also present as free linear polysaccharide chains, called heparan sulfates. HS and its monosulfated derivatives, such as syndecan and dermatan sulfate, are found on the surface of extracellular matrix and as components of proteoglycans in the BM and other tissues.

In intact normal skin, heparan sulfates are localized on the BM and vascular capillaries. Up to two months after wounding, the aesthetic skin care shop heparan sulfate epitope is absent in the neo-epidermal BM of the regenerated skin. However, by one year after wounding, the heparan epitope is once again present in the neo-epidermal skin, indicating that complete re-establishment of a functional BM is a slow process.

To accelerate the re-establishment of BM function, we have developed an anti-wrinkle ingredient by conjugating a heparan sulfate peptide with vitamin C using ascorbyl succinyl tetrapeptide (AST). The resulting heparan sulfate-vitamin C complex has been shown to stimulate BM protein expression and enhance the DEJ by promoting epidermal cell proliferation and migration.