70 SKIN CARE Keratinocytes.13 This paper will review and

expand on this discovery and discuss possible implications of this protein’s stimulating effect on skin barrier and overall skin health.

Materials and methods The Methods employed in these studies were reported on in an earlier publication.13


active product employed in these studies is a product sold commercially by BotanicalsPlus14 known as BP—Triluronic Acid. The complex is comprised of three molecular weight fractions of HA that include a high molecular weight fraction (1.5-2.0 MDa), a medium molecular weight fraction (200-500 kDa) and a low molecular weight fraction (5-10 kDa). The ingredient is offered in solution, powder and anhydrous formats. The following were employed for the study:

■ 1% BP—Triluronic Acid Solution (active) ■ Normal (Adult) Human Epidermal Keratinocyte Cells (medium) ■ Dibutyryl Cyclic-Adenosine Monophosphate (DbcAMP) (control) DbcAMP is a cell permeable form of cAMP. It

was used in these studies as a positive control because it is known to increase hyaluronic acid synthesis in fibroblasts and keratinocytes.15

Results and Discussion The skin cells examined in the reported studies were Normal Human Epidermal Keratinocytes (NHEKs), the same cells that create the skin’s epidermis. The results of the treatment of the NHEKs with concentrations of BP—Triluronic® Acid are shown in Figure 2. As is well-known, the skin’s epidermis is not a static structure, but is a constantly evolving protective covering in which keratinocytes slowly migrate from

200 180 160 140 120 100 80 60 40 20 0

* *


DbcAMP Treatment

Figure 2: Results of ECM-III assay comparing protein expression in pg/µg of protein expressed showing Untreated keratinocytes, cells treated with DbcAMP (positive control) and cells treated with 1.0% BP— Triluronic® Acid. Asterisks indicate statistical p<0.05 significance against Untreated control cells.

the lower levels of the epidermis upwards to the surface of the skin. This process is called differentiation, as the living keratinocyte cells slowly die and change into hardened keratin-based structures called corneocytes. The keratinocytes within the epidermis are held together by proteins called Tight Junction Proteins that are stimulated by expression of Hyaluronic Acid in the skin.16

During the

process of changing, the keratinocytes also express lipids in a profoundly important way—such that the dead corneocytes reside in a mortice of lipids, called the lipid bilayer, that create the stratum corneum.17

Recent elegant cryo-electron microscopic studies

of this process have demonstrated that what seems like a simple process is anything but and the corneocyte/lipid barrier that is formed is a very complex and constantly differentiating structure.18

BP-Triluronic® Acid Solution 1%

The entire structure

of the dynamic skin barrier has been generally referred to as a “brick and mortar” structure. When the stratum corneum is disrupted, the impact can, depending on the degree of disruption, be very serious. For example, in wounds like skin burns, the stratum corneum disruption can be so serious that the body loses water very rapidly and if the water is not replenished fast enough, it can result in death. The body’s skin keeps the human body from dehydrating in an earthly environment that would normally desiccate the body in days. Interestingly, the process of cellular

differentiation and lipid bilayer formation is controlled, much as a conductor controls the sounds of an medley, by the complex formed between the skin’s Hyaluronic Acid and the Hyaluronate Receptor proteins. When HA binds to these proteins, the interaction signals a commencement of a sophisticated molecular orchestra of skin barrier development.

If there is a disruption in this

finely tuned orchestral arrangement, much as an instrument playing out of tune can throw off an entire song, improper signalling of the glycoprotein conjugate can throw off normal skin barrier formation and skin health. While it was known in the literature that

various molecular weight fragments of HA interact with various transmembrane proteins, what was unknown prior to the work reported here was that Hyaluronic Acid itself can stimulate the formation of additional ECM-III proteins in NHEKs.19

Simply put, HA has the

Figure 3: Schematic representation of BP-Triluronic Acid polysaccharide complex showing how the High MW fraction (1.5-2.0 MDa) and medium MW fraction (200-500 kDa) would tend to reside at the surface of the skin (left image) while the Low MW fraction (5-10 kDa) would penetrate below the Stratum Corneum and be able to contact the viable Epidermis containing the Keratinocyte cells examined in the studies reported (right image).


ability to prompt more Hyaluronate Receptor proteins to be produced in the epidermal cells—which plays a big role in supporting the skin barrier, among other skin benefits.

Conclusion It has been found that a concentration of 1.0%

pg/ug Protein

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