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Renaissance CLINICAL STUDIES Siegesbeckia Orientalis Extract

Siegesbeckia Orientalis Extract is obtained from the herb Siegesbeckia orientalis L. This herb has been used for centuries externally to soothe inflammation and stimulate wound healing, which it does through tissue regeneration by way of collagen matrix build-up.

A now expired patent by Pierre Fabre Medicaments describes its ability to stimulate wound healing, to promote more regular tissue renewal, to increase the normal appearance of scars and to fully restore elasticity to damaged skin with collagen fibers arranged in regular fashion.

Extracts of Siegesbeckia orientalis have shown anti-inflammatory properties, inhibition of collagenase and protection from UV induced erythema.

This initial research led to an investigation of Siegesbeckia Orientalis Extract ability to restructure stretch marks. Stretch marks are caused by abnormal stretching of the dermis (pregnancy, change in weight), from a linear scar or from some endocrine disorders. In each case the stretch mark affects the elastin fibers in the middle dermis, which are diminished or disappear. Any effective treatment for stretch marks thus must restore normal quantities of collagen and elastin fibers.

The effects shown in a four-week clinical study where a crème containing 1.5% of Siegesbeckia Orientalis Extract was applied by volunteers twice daily are listed below.

Results

Length of Streaks -- Reduced 52.15%

Surface Smoothness -- Increased 13.7%

Indented Surfaces -- Reduced 55.4%

Length of Irregularities -- Reduced 52.2%

These results correspond to restructuring of the tissue. At the end of treatment the surface of the skin was more regular in appearance and the global profile was more uniform with stretch marks tending to fade. These results show Siegesbeckia Orientalis Extract to possess exciting characteristics for the treatment of stretch marks. In addition, Siegesbeckia Orientalis Extract is shown to possess excellent tolerance and non-toxicity.

Emblica

Emblica is the trade name for a tannin-rich extract from the herb Phyllanthus emblica. This herb has been used for thousands of years in India and is a cornerstone within the traditional healing system of Ayurveda.

As a skincare ingredient Emblica has been shown to have great multifunctionality. Though its primary applications within the skincare industry are as a photoprotective agent and a skin lightener, Emblica offers a host of benefits for the skin.

Studies have shown Emblica to possess powerful, broad-spectrum antioxidant properties. In addition, Emblica is extremely stable and is not subject to photodegradation. While vitamins C, and E, and antioxidants from pine bark and rosemary lose over 50% of their antioxidant activity in an aqueous solution after only three months, Emblica remains stable for over a year. Research has shown Emblica to increase skin hydration and skin lipids, to reduce collagenase activity, to reduce UV-induced erythema, to reduce inflammation and to help preserve skin tone and integrity.

One of Emblica’s most exciting applications is as a skin lightener. While most skin lighteners such as Hydroquinone, Arbutin, and Kojic Acid have toxicity issues or can cause negative reactions on the skin, Emblica is well tolerated with no side effects. Magnesium Ascorbyl Phosphate has been the best-tolerated skin lightener up to this point, however Emblica is more stable and does not generate pro-oxidant activity.

Skin lightening agents are used to either lighten or depigment the skin. Skin lighteners are generally used in Europe and the United States to treat age spots and freckles whereas the Asian market uses them to change or modify skin color. Excessive pigmentation of the skin can be caused by UV-radiation, hormonal imbalance, inflammation, drugs or aging. A number of studies have demonstrated Emblica’s ability to lighten and even-tone normal, hyper-pigmented and UV-induced pigmented skin color. In two studies Emblica showed comparable results to an equal concentration of Hydroquinone for skin lightening with Hispanic and Asian skin over a nine-week period. Another study showed Emblica to provide significant lightening of freckle spots after 8 weeks.

Though there has not been a specific study of Emblica’s potential to normalize the uneven skin tone caused by stretch marks, its ability to lighten both normal and hyper-pigmented skin is perhaps an indication that Emblica could also play a role in helping to normalize the appearance of stretch-marked skin.

As mentioned above, Emblica also possesses exciting photoprotective properties. Of particular importance is Emblica’s ability to reduce collagenase activity (a protein that attacks the dermis), which is increased by UV light. Collagenase is one of the key factors in aging of the skin.

Another extremely important feature of Emblica is that it can chelate iron and copper.

While iron and copper are necessary for many biological activities, their toxicity threatens cellular integrity. Emblica seems a particularly good ingredient to add to sun protection products, as it is clear that UV radiation causes the release of iron in skin firbroblasts and that sun-damaged skin contains significantly higher levels of iron.

While antioxidants are the chief defense against free radical damage, vitamins C and E as well as glutathione all function as pro-oxidants when in the presence of iron and copper, causing additional oxidative stress. Emblica may play an increasing role in UV protective products because it can help reduce oxidative stress by scavenging free radicals while simultaneously chelating iron and copper, stopping their harmful effects.

Emblica is extremely well tolerated with no adverse side effects.

Palmitoyl Pentapeptide-3

Palmitoyl Pentapeptide-3 is a synthetic protein that is a fragment of the C-terminal portion of collagen I (the most common type of the nineteen forms of collagen) combined with palmitic acid to make it more lipophillic, to improve its stability and to enhance its affinity towards human skin. One could look at Palmitoyl Pentapeptide-3 as a man-made precursor to collagen I. When this protein is added to cultured human fibroblasts it enhances the synthesis of collagen I, collagen III and fibronectin.

The research behind Palmitoyl Pentapeptide-3 was begun to find specific solutions to address aging factors in the skin, particularly the thinning of the sinusoidal layer between the dermis and the epidermis. The goal was to find a short peptide that would stimulate fibroblasts in the skin to produce key components of the extra-cellular matrix such as collagen and hyaluronic acid. The reasons for this follow.

As we age, the skin gets thinner. Part of this process is that the sinusoidal dermo-epidermal interface layer between the dermis and the epidermis gets flatter. It is this layer that allows nutrients to flow from the dermis to the epidermis. As we age this layer gets flatter and this reduces the area of exchange interface between the dermis and the epidermis. This can significantly affect the quality of the epidermis. The loss of adhesion between these two structures, which is normally provided by collagen IV and collagen VII, results in nutritional exchange deficiencies and a slowing of biological processes in the skin.

Collagen is the main constituent of the skin’s extra-cellular matrix. In fact, collagen as a whole makes up approximately 25% of all protein found in the human body. In young skin, the collagen fibers are held in place by orderly bonds, to form a sort of net. The “holes” of this net are filled by proteoglycans and glycosaminoglycans forming the glycan network. The glycan network is a water-saturated gel in which water-soluble molecules and ions are able to circulate. It is this water that gives skin its visco-elasticity and its turgidity. A key molecule in this process is hyaluronic acid, as it can hold up to 1000 times its weight in water. A reduction in the quantity of interstitial glycans (including hyaluronic acid) leads to a loss of water retention and the glycan network collapses onto itself. With age, this gel tends to sag, hindering cell migration and mitosis. As the number of fibroblasts, mastocytes and blood vessels falls, the dermis atrophies.

Studies were carried out to see if Palmitoyl Pentapeptide-3 would affect the sinusoidal dermo-epidermal interface layer and if it would help to stimulate factors making up the glycan network. As mentioned above, collagen IV and collagen VII are the primary constituents of the sinusoidal dermo-epidermal interface layer between the dermis and the epidermis that allows nutrients to flow from the dermis to the epidermis. In vitro, Palmitoyl Pentapeptide-3 was found to stimulate collagen IV synthesis by 100-327% and to stimulate hyaluronic acid synthesis by 267%. In vivo Palmitoyl Pentapeptide-3 was found to stimulate collagen synthesis by 30-117%. The next step was to use image analysis to determine the affect Palmitoyl Pentapeptide-3 had on wrinkled skin. The six-month results are listed below, though significant results were seen in two months.

Results Mean wrinkle depth -- Reduced 17%

Surface area – deep wrinkles -- Reduced 68%

Surface area – moderate wrinkles -- Reduced 51%

Mean density of wrinkled area -- Reduced 47%

Skin roughness -- Reduced 16%

Main wrinkle volume -- Reduced 24%

These results show that Palmitoyl Pentapeptide-3 had a dramatic effect on reducing the quantity and depth of wrinkles. It also improved surface smoothness. The studies behind Palmitoyl Pentapeptide-3 give a clear description of the mechanism for how this is accomplished and also indicate that Palmitoyl Pentapeptide-3 is stimulating natural biological processes to reverse the aging process of the skin. In addition, Palmitoyl Pentapeptide-3 is very well tolerated by the skin. Palmitoyl Pentapeptide-3 is a very exciting ingredient and is becoming more and more popular as its results are becoming more widely known.

Biopeptide-CL Like Palmitoyl Pentapeptide-3, Biopeptide-CL is a synthetic protein that is a fragment of collagen combined with palmitic acid to make it more lipophillic, to improve its stability and to enhance its affinity towards human skin. As with Palmitoyl Pentapeptide-3, one could look at Biopeptide-CL as a man-made precursor to collagen.

Biopeptide-CL was developed through research to identify a substance that would behave similarly to retinoic acid but without its drawbacks, especially in regards to synthesizing collagen.

The reported results are as follows:

In vitro:

Increases collagen production by the fibroblasts by as much as 350%.

Increases hyaluronic acid production by the fibroblasts by as much as 146%.

In vivo:

The following statistics were gathered using image analysis of volunteers who used crèmes containing a 3% concentration of Biopeptide-CL for 28 days.

Surface roughness -- Reduced 17%

Mean depth of wrinkles -- Reduced 23%

Depth of main wrinkle -- Reduced 39%

Skin thickness -- Increased 4%

The increase in skin thickness was considered especially notable and contrasts with the 6% reduction of the skin thickness that occurs after 10 years of aging. The study concludes to state that Biopeptide-CL is a potent active cosmetic ingredient without the adverse effects (including irritation, dehydration or long-term toxicity and instability) characteristic of retinoids.

Palmitoyl Tetrapeptide-3

Palmitoyl Tetrapeptide-3 is a synthetic peptide that is a fragment of immunoglobulin G that has been combined with palmitic acid to make it more lipophillic and thus enhance its affinity towards human skin. Palmitoyl Tetrapeptide-3 was discovered through research to learn how to suppress the body’s production of interleukins, particularly IL6, since these are the chemical messengers that trigger the body’s acute inflammatory response.

Inflammation is a function of immunity and is a protective response to injury or destruction of tissue. This is the body’s way of walling off the injurious agent and the injured tissue. Under normal circumstances, very little IL6 is secreted and its secretion is strictly controlled. However, as we age this regulation system develops defects, and significant levels of IL6 appear in the plasma even when there is no inflammatory stimulus. This results in high levels of inflammatory proteins in the tissues and a loss of healing potential. This process has been linked with breast cancer, osteoporosis, anemia, autoimmunity and slower tissue regeneration.

The hormone DHEA is directly responsible for maintaining the regulation of the production of IL6. This has even been demonstrated in the skin: when DHEA is present in sufficient amounts it is converted into a steroid hormone, androstenediol, which is directly responsible for maintain IL6 production and for maintaining local homeostasis of cytokine and interleukin production. As we age, DHEA is reduced and this directly leads to cytokine deregulation and the over-production of some interleukins and the under-production of others. As mentioned above, IL6 production is increased with negative consequences. Since UV radiation can increase IL6 production by five times, this process can significantly impact the skin.

The researchers’ goal thus became to find a peptide that would mimic the effects of DHEA without DHEA’s potential for being converted into estrogen, since estrogen is a hormone that is not licensed for cosmetic purposes. Specifically they wanted to find a peptide that would target IL6 and inhibit its production. The results:

1.) At concentrations from 10 ppm, Palmitoyl Tetrapeptide-3 induces a marked reduction in the secretion of the cytokine IL6. This reduction is progressive and depends on the concentration of the peptide: baseline secretion may be inhibited by up to 40%.

2.) Palmitoyl Tetrapeptide-3 reduced levels of IL6 after cells were exposed to UV radiation by up to 86% even though IL6 had been increased by about 20 fold by the UV.

These results show that Palmitoyl Tetrapeptide-3 is able to affect baseline levels of IL6 as well as modulate the effects of UV-stimulated over-production of IL6. IL6 is marketed by Sederma as a molecule that can restore cytokine equilibrium, which characterizes youthful skin. Ultra Aesthetics has chosen to use Palmitoyl Tetrapeptide-3as a synergistic support ingredient to create a more optimum environment for other active ingredients to help restore youthful skin appearance.

Acetyl Hexapeptide-3

Acetyl Hexapeptide-3 is used in formulas as a wrinkle preventative as well as a wrinkle reducer as an alternative to injections.

Acetyl Hexapeptide-3 is a mimic of the N-terminal end of SNAP-25, one of three proteins (known as the SNARE complex) that are essential for neurotransmitter release at the synapsis, which is the chemical signal for a muscle to contract.

As a wrinkle reducer, studies have shown that Acetyl Hexapeptide-3 at a 10% concentration was able to significantly decrease the depth of wrinkles after 30 days of treatment. The mechanism by which Acetyl Hexapeptide-3 is able to accomplish this is related to the ways in which Acetyl Hexapeptide-3 is able to assist wrinkle prevention.

Acetyl Hexapeptide-3 performs this activity in two distinct ways:

The first way Acetyl Hexapeptide-3 acts as a wrinkle preventative is by competing with SNAP-25 for a position in the SNARE complex. This destabilizes the SNARE complex, preventing the vesicle from releasing neurotransmitters efficiently, and therefore attenuating muscle contraction. This causes a reduction in facial muscle contraction, which is believed to help prevent the long-term formation of lines and wrinkles.

The second way that Acetyl Hexapeptide-3 acts as a wrinkle preventative is by reducing the release of catecholamines (the overproduction of which is known to induce the formation of wrinkles and fine lines in the skin), specifically adrenaline and noradrenaline.

Acetyl Hexapeptide-3 is non-toxic and well tolerated by the skin.

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