Highly Polymerised DeoxyRibonucleotide (HPDR) or DNA is a molecule well known to biologists since the fundamental works of Watson and Crick and continues to attract a lot of attention.
Its structure is that of a natural polymer of which the basic element (which can sometimes be improperly called DNA within the cosmetic industry) is the association of three molecules: phosphorous, deoxyribose and a nucleic base (adenine or thymine or cytosine or guanine), which then form a nucleotide. The nucleotides in a chain constitute a long molecule, where the repetition of the various motifs is at the origin of the genetic code. This is now well documented and understood. The natural macromolecule is in reality formed by two chains coiled in the classic way of the double helix of which Watson and Crick described. This particularity brings into existence loose links called ‘hydrogen bonds’, between the complementary bases [Adenine (A) – Thymine (T) – Guanine (G) – Cytosine (C)] and are links susceptible to coming apart and joining in natural biological conditions. Only this tertiary spatial structure defines this natural polymer and therefore its biological characteristics, in opposition to the basic chemical units or monomers which are nucleotides alone or associated in a short chain. The industrial production of such a DNA, (called HPDR or integral DNA) is the preliminary indispensable condition for all biological and therapeutic uses of this molecule. In effect, the practical research and development of the method of extraction, specific to the biological raw material selection (salmon milt), allows for the integral preservation of the molecular structure. The HPDR (now referred to as integral DNA in this article), is characterised by:
• Its origin (derived from salmon spermatozoa).
• Its particular extraction method.
• Its perfectly defined physico-chemical properties.
Its fibrous appearance is a characteristic of the double helix super organisation of the biopolymer. Integral DNA extraction is done by non-denaturing techniques allowing perfect protection of its superstructure and so, preserving its physiological activity. The biological extracts made with nonpolymerised nucleotides cannot, under any circumstances, lay claim to the multiple biological functions of integral DNA. We obtain DNA according to strictly controlled conditions and therefore the molecule complies with precise physicochemical criterion which ensures that it does not contain inactive depolymerised parts. Javenech’s research centre, alongside the pharmaceutical industry has been working on this technique for many years. It has analytical, toxico-pharmacological and clinical files which may be required to obtain government approvals for use in finished products. The results of the toxicological studies allow for very safe use. At last, some of the acknowledged pharmacological and clinical properties can be of interest to the cosmetic industry.
Natural active against UV rays
In addition to its biological effects, the integral DNA molecule has an important physical characteristic: the partial protection against the diffusion of UV radiation. When applied very thinly (1 mm), a 1% integral DNA solution absorbs all weak intensity UV rays between a 200 mm and 300 mm wavelength (Fig. 1).1,2 Integral DNA, placed on the skin surface, will be able to block out part of the UV ray diffusion to the skin (the same wavelength that destroys the DNA cell). The addition of integral DNA in a sun care product enhances its photo-protective action (Fig. 2),3 by remedying the deficiencies in the barrier effectiveness of solar filtering and preventing and curing the eventual damage caused by UV rays to the skin. Further, its moisturising and antioxidant activity will allow safe sun tanning. In addition, integral DNA depolymerises but does not form toxic breakdown products. In view of the ageing phenomenon by exposure to UV solar rays, the cellular DNA of the epidermis undergoes damage for the same reason. The protective application of DNA in a gel form captures the nocuous UV rays and so protects the cell nucleus within the skin.
Antioxidant activity
An antioxidising activity (Fig. 3)4 takes place with the trapping of OH• radicals within the double helix, (this activity improves the effects of alpha tocopherol). In addition to this free radical scavenging activity, the integral DNA biomolecule presents another advantage in comparison with most other substances of the same activity. After scavenging free radicals, it does not form new toxic derived radicals that are able to damage other neighbouring components (the attack of OH• radicals upon integral DNA proceeds by addition and gives 8-OH deoxyguanosine). Rates of reactions in polymerised molecules have been reported.5 By evaluation of the expression of several genes by microcomputer-chips with DNA (cDNA-array gene expression) on normal human keratinocytes,6 we recorded an activation of several genes (TFRC, +4812% –FTH1, +153%); activation of the ferritin and the transferrin receptor. Integral DNA has an effect of protection against the toxicity of iron in the scavenging reactions (ROS – reactive oxygen species). For example, after UV exposure, the quantity of ferritin increases to complex iron and thus avoids its catalyst effect on free radicals.
Rebuilding of the cutaneaous damage
By evaluation using the same cDNA-array gene expression on normal human keratinocytes,6 we recorded an activation of several genes (CRNN, +335% –RPTN, +255% –TNF, +225% –SFN, +247%). Cornulin is a (cornified) stratified squamous epithelial protein that is considered a marker of late keratinocyte differentiation. The repetin is necessary to the formation of the corneal envelope. Stratifin is strongly induced by gamma radiation and other DNA-damaging agents (answer to an infection or inflammation).
Conclusion
HPDR is a natural, non toxic ingredient that can improve the UV protection of cosmetic products without the formation of toxic breakdown products. In addition to its free radical scavenging activity, the ingredient can rebuild cutaneaous damage by its power of hydration and anti dehydration.
Other advantages in cosmetic formulations
Hydration and anti-dehydration (Figs. 4-6)
Owing to the rigidity of its double helix structure and its great length compared with its diameter, integral DNA has considerable water retention qualities. When this molecule diffuses through the cells, it carries a water volume 10,000 times greater than its own volume.7 Using cDNA-array gene expression on normal human keratinocytes,6 we recorded an activation of several genes (AQP3, +652% –AQP8, +103% –SPTLC1, +777%). Integral DNA stimulates the aquaporins and serin palmitoyltransferase. Aquaporins are membrane water channels that play critical roles in controlling the water contents of cells (maintenance of hydrous balance). Serin palmitoyltransferase is an enzyme necessary for the synthesis of the ceramides phospholipides that play a ‘cement’ role between the horny layer corneocytes (barrier effect, avoids dehydration).
Antilipoperoxidant properties
Its antilipoperoxidant properties (by OH• radical scavenging) can be beneficial in creams in order to protect against oxidative deleterious effects of creams containing polyunsaturated fatty acids (Figs. 7 & 8).8
Elastase inhibition
Integral DNA is capable of inhibiting elastase, specifically the fibroblasts elastase in the human skin, which is largely responsible for the destruction of elastic fibres of the derma during the process of ageing (Fig. 9).9
Healing
The healing properties have been shown on corneal wounds and aspirin ulcers. In the cornea, integral DNA binds and heals wounds and explains its tolerance by the mucous membrane of the eye.10 Thus the integral DNA molecule is an excellent cosmetic active ingredient for products that outline the eye. Further, integral DNA protects against the effects of aspirin ulcers by again, binding and healing ulcer wounds. This can be a benefit after treatment with AHA or retinoic acid Also, some in vitro experiments show that integral DNA stimulates the collagen and proteoglycan synthesis which acts against the destructive effects of ageing in the skin.11,12 A stimulant activity towards ciliary motricity of cells previously inhibited.13 Integral DNA’s polymerisation structure, as well as its physico-chemical properties, allow the binding of some environmental toxic heavy metals such as lead or cadmium found in cigarette smoke or other sources of pollution (Figs. 10 & 11).14 When it is applied to the skin, integral DNA reveals its pharmacological properties thanks to three mechanisms:
• A direct action on the cellular growth by the diffusion of metabolites resulting from its degradation.
• An indirect signal effect sent by these metabolites fostering further cellular growth.
• A passage of the integral DNA molecule through the upper layer of epidermis, thanks to the torsion capacities of deoxyribonucleic acid. That would be a physical penetration, linked with possible dilatation of intercellular spaces, notably in the presence of excess water. These spaces, the content of which is essentially lipidic, can let hydrophilic molecules pass slowly.
Conclusion
The HPDR molecule is a natural macromolecule from the sea and, thanks to its total innocuousness and high cutaneous activity, it belongs to the best active ingredients in the cosmetic industry. Its numerous properties enable it to be used for successful marketing operations. HPDR can improve the UV protection of cosmetic products without formation of toxic breakdown products. In addition to its free radical scavenging activity, HPDR can rebuild the cutaneaous damage with a high power of hydration and anti-dehydration. Associated with a specific cosmetic formula, the HPDR molecule enhances the protective capabilities within other active ingredients. PPCC
References
1 Integral DNA and the treatment of cutaneous ageing. Parfums, Cosmétiques, Arômes n°65 – Octobre-Décembre 1985; 77. 2 In vitro behavior of HPDR raw material after exposure to UV radiation. 3 Clinical assessment of the Sun Protective Factor of HPDR. 4 Free radical scavenging activity of biopolymere composed of HPDR (review). 5 Sonntag CV. The chemical basis of radiation biology. London: Taylor and Francis Press, 1987. 6 HPDR and expression of several genes by microcomputer-chips with DNA (cDNA-array gen expression) on normal human keratinocytes. Javenech study 2008 7 Lehninger. 8 Study of protective effect of HPDR against lipid peroxidation. 9 Elastase inhibition by HPDR. 10 Clinical trials of HPDR on eye corneal wounds. 11 Advantages of HPDR in arthrosis recovery. 12 Advantages of HPDR in arthrosis recovery. Dr Mitrovic, C.H.U. Lariboisière; Dr Charlot. C.H.U. Henri Mondor, Créteil; Pr M. Richard, Hôpital Edouard Herriot, Lyon. 13 Stimulant activity toward ciliary motricity of cells previously inhibited. Chevance, Pasteur Institute. 14 Evidence of protective effects of biological polymers against heavy metals (lead and cadmium).
