Future Cosmeceuticals of Dermatologic Importance

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Chapter 32 Future Cosmeceuticals of Dermatologic Importance

Neil S. Sadick

INTRODUCTION

As the aging population grows and the choice of cosmeceuticals becomes ever more discrete, cosmetic composition is essential in the antiaging field. But it is vital that the force behind innovative skin care lines is both clinical and scientific. This new generation of cosmeceuticals focuses on cell protection from both environmental and genetic forces.

ANTIOXIDANTS

Our skin is continuously exposed to oxidative stress leading to accelerated aging by damaging DNA, lipids, and proteins. Various endogenous antioxidant systems are designed to protect us from these oxidative stresses. Oxidative stress results from many sources including genetics, environmental factors, and ultraviolet (UV) radiation. The action mechanism of antioxidants in induction is such that they prevent free radicals from forming chain reactions that have the capability of damaging cells during oxidation of other molecules. Antioxidants are comprised of various molecules such as alpha lipoic acid (ALA), coenzyme Q-10, polyphenols, idebenone, kinetin, and vitamins A, B, C, and E. Antioxidants are widely used as treatments in many human diseases and have now become a vital source in cosmeceuticals because of their strong photoprotective effects, thereby resulting in reduction of erythema, sunburn cell formation, DNA changes, and carcinogenesis Fig. 32.1.

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Fig. 32.1 Free radical theory of aging

POLYPHENOLS

Polyphenols are groups of chemical substances with diverse and complex chemical structures that are found in plants. Flavonoids are one subgroup of polyphenols, including grape seed extract and soy isoflavones. Flavonoids are found in a large variety of foods, thus a diet high in phytochemicals along with topical application may protect the skin from endogenous and exogenous stress. It is believed that polyphenols not only protect cells from further damage but also promote cell revival. A study was conducted to measure the extent of effectiveness of polyphenols on UV skin damage. Epigallocatechin-3-gallate (EGCG), one of the main components of green tea, has been reported to have anticarcinogenic effects on the skin when exposed to UV radiation. In one study mice were exposed to UVB twice a week for 20 weeks (radiation dose between 280 and 375 nm). Some of the mice were then treated topically with EGCG (3.0 mg, 6.5 μmol) five days a week for 18 weeks. Some of the mice were treated with caffeine. Tumor formation was measured. The control group, which was exposed to UVB but was not treated with anything, developed an average of 4.5 tumors per mouse after 12 weeks. The caffeine-treated group developed 1.3 tumors per mouse and the EGCG-treated group developed 0.8 tumors per mouse. After 18 weeks, the control group developed 6.9 tumors while the caffeine and EGCG groups developed 3.6 and 2.5 tumors respectively.

GENISTEIN

Genistein is a soybean isoflavone that was first isolated from soy beans in 1931. It is a potent antioxidant with specific inhibitors of protein tyrosine, kinase, and phytoestrogens, increasing the thickness of the skin through an estrogenic effect. It has been found that it exhibits properties preventing the hemolysis of red blood cells by dialuric acid or H2O2 and inhibiting microsomal lipid peroxidation induced by Fe2+-ADP complex and NAPDH. It is the most potent inhibitor of P450-mediated activation of benzo[a]pyrene among all isoflavones.

Multiple studies over the past decade have given support to the belief that these natural ingredients have preventive and therapeutic effects on breast and prostate cancers, osteoporosis, cardiovascular diseases (in humans and animals), and postmenopausal syndrome. Genistein has significant effects in terms of inhibition of chemical carcinogenesis, UV-induced skin carcinogenesis and photo-damage in both humans and mice.

Although numerous in vitro studies have shown its potential in anticancer properties, evidence is lacking on its effect on skin carcinogenesis, but there is scientific support for its potential. Genistein has been found to have chemopreventive and strong anticancer activities. It has been shown to inhibit the activity of tyrosine protein kinase (TPK), topoisomerase II (Topo II), and ribosomal S6 kinase (RS6K) in cell culture. It has also been shown to inhibit growth of the ras oncogene and decrease PD6F-induced c-fos and c-jun expression in fibroblasts. Experiments were conducted to prove that genistein substantially blocks subacute and chronic UVB- and PUVA-induced cutaneous damage (Box 32.1; Figs 32.2 and 32.3).

Box 32.1 Clinical effects of genistein

image Preventive and therapeutic effects on the following in animals and humans:

Breast cancer

Prostate cancer

Postmenopausal syndrome

Osteoporosis

Cardiovascular disease

image Inhibits chemical carcinogen and UV light-induced skin carcinogenesis, photoaging, and photodamage

image Inhibits skin tumor formation post UVB radiation

image

Fig. 32.2 (A–C) Effect of genistein on UVB-induced acute skin burns in mice

image

Fig. 32.3 (A–C) Effect of genistein on histologic alterations in mice exposed to UVB

IDEBENONE

Idebenone, a newly developed antioxidant, is based on sunburn assays, photochemiluminescence, primary and secondary oxidative product assays, and evaluation of damage to UVB-irradiated keratinocytes. Idebenone is a powerful antioxidant outperforming many others. It has the capability of penetrating deep into the dermal layer of the skin and destroying free radicals associated with exposure to UV radiation. A five-part study to measure the environmental protection factor (EPF) and the safety and efficacy of idebenone was conducted. For each part of the study the highest possible score was 20 points for a total of 100. Idebenone was rated 95 out of 100 points in improvement of fine lines and wrinkles, radiance, dry and photodamaged skin, and elasticity (Table 32.1).

Table 32.1 Mechanism of aging based upon the free radical treatment of oxidative stress

image

GLOBAL REJUVENATION AGENTS

• Vitis vinifera

Vitis vinifera is a grape seed extract rich in flavonoids and phytochemicals. This grape seed extract is used in facial creams throughout Europe and is known to be much more effective than vitamins E and C on keratinocytes after H2O2 exposure. The grape seed extract is used in treating diseases of the skin, such as psoriasis and eczema, by blocking the disruption of the chemical structure of enzymes used in collagen building. Bioflavonoids in the extract promote fast absorption into the skin. These oxidative properties are also used in treating various other ailments and diseases such as preventing heart disease by acting as an anticoagulative agent, minimizing fibromyalgia damage by protecting muscle cells, lessening allergy symptoms as it acts as a natural antihistamine, deterring cancer by neutralizing the cellular change of the genetic material within a cell that may result in tumor formulation, slowing the progression of macular degeneration, and regulating hepatic architecture.

In one study comparing a serum and a cream versus a serum, both of which contained the Vitis vinifera shoot extract (grape seed), 26 subjects used the serum twice a day for 28 days and 30 subjects used the serum and cream twice a day for the same time period. The treatment area was the face and neck. Improvement in firmness, radiant glow, softness, texture, fine lines and wrinkles were tracked. There was no significant difference in findings between the serum and cream and the serum group. Fifty-four percent of the serum-treated subjects noted an overall global improvement greater than 25% (using a quartile scale) while 60% of the serum and cream group noted equal improvement.

• Coffeeberry

Coffeeberry is an antioxidant that is a combination of mequinol 2% and tretinoin 0.01% and is rich in polyphenols. In a randomized, double-blind, in vitro study, coffeeberry aided in the reduction of hyperpigmentation as well as enhancing collagen production in fibroblasts. It protects from harmful UVA/UVB rays. Coffeeberry derives from the coffee cherry which is the outer fleshy coating of the coffee seed. It is said to have higher potency than strawberries, blueberries, and raspberries, as well as white and green teas. Research conducted over a 6-week period showed significant reduction in hyperpigmentation, fine lines, and wrinkles. Patients with sensitive skin did not suffer from irritation.

• Stem cells

Wrinkles are due to cellular rarefaction in the interfollicular epidermis, leading to a loss in substance of essential fibers and, more importantly, the loss of stem cells (keratinocytes) which have extraordinary regenerative power. The natural aging process and oxidative stress are contributors to the depletion of these vital cells. Stem cells are undifferentiated cells that are capable of rejuvenation. The ability to capture and manipulate that capacity has far-reaching implications in the field of medicine. It may be used to treat a wide range of diseases. One particular use is in wound healing and tissue regeneration. The natural extension would be to utilize this technology in the field of rejuvenation by focusing on the skin’s ability to repair itself. This particular field has spilled over into the area of cosmeceuticals. Research is still nascent in this area.

• Aquaporins

Due to extreme temperatures as well as the normal process of aging, our skin loses its elasticity creating a ‘hydric stress’ that stimulates our aquaporin network to help bring our body back to homeostasis. This network works on bringing water from the inside to the outermost layer of the skin where dehydration occurs first hand. When we are exposed to extreme temperatures we are subjected to transepidermal water loss, which is how the skin loses its hydration, causing fine lines and wrinkles. Therefore, optimal water circulation is essential in dehydration prevention.

Aquaporins serve as ‘plumbing systems’ in the generation of our bodily fluids. They transport water from the deepest cell layers to the ones closest to the surface. A product was formulated called hydraction-Aquacapt complex that promotes better water circulation between cells. This complex contains Aquaxyl, a synthetic combination of molecules derived from wheat and birch. It stimulates the production of water levels in the skin’s epidermal layer and decreases loss from evaporation.

• Peptides

Peptides serve as messenger vehicles between the dermal and epidermal layers of the skin, enabling efficient communication between cells. In a number of peptide studies conducted to test their efficacy in cosmeceuticals, the most effective proved to be pal-pentapeptide (pal-KTTKS), composed of lysine, threonine, threonine, lysine, and serine. It has been used in combination with palmitic acid for enhanced penetration into the skin for stimulation of cellular growth of collagen and fibronectin synthesis. A 4-month study was conducted with applications of twice-daily medication on the face and neck. Results showed a decrease in roughness of the skin by 13%, reduction in fine lines and wrinkles by 36%, and a decrease in wrinkle depth by 27%. Pal-KTTKS increases elastin fibers and regulation of collagen IV at the skin junction Fig. 32.4.

image

Fig. 32.4 Signs of aging: decrease after a 4-month study

CONCLUSION

In addition to the high efficacy of antioxidants, such as polyphenols and coffeeberry, which aid in the prevention of many human diseases and in the alleviation of photoaging of skin, the future generation of cosmeceuticals focuses on global rejuvenation. This new approach to skin care centers on the reversal of aging.

FURTHER READING

Akiyama T, Ishida J, Nakagawa S, et al. Genistein, a specific inhibitor of tyrosine-specific protein kinases. Journal of Biological Chemistry. 1987;262:5592–5595.

Albertazzi P, Pansini F, Bonaccorsi G, et al. The effect of dietary soy supplementation on hot flushes. Obstetrics and Gynecology. 1998;91:6–11.

Arora A, Nair MG, Strasburg GM. Antioxidant activities of isoflavones and their biological activities in a liposomal system. Archives of Biochemistry and Biophysics. 1998;356:133–141.

Brzezinski A, Adlercreutz H, Shaoul R, et al. Short-term effects of phytoestrogen-rich diet on postmenopausal women. Menopause. 1997;42:89–94.

Cai Q, Wei H. Effects of dietary genistein on antioxidant enzyme activities in Sencar mice. Nutrition and Cancer. 1996;25:1–7.

Correa P. Epidemiological correlations between diet and cancer frequency. Cancer Research. 1981;41:3685–3690.

Cornacchione S, Neveu M, Talbourdet S, et al. In vivo skin antioxidant effect of a new combination based on a specific Vitis vinifera shoot extract and a biotechnological extract. Journal of Drugs in Dermatology. 2007;6:S8-S18.

Draelos Z. Botanical antioxidants. Cosmetic Dermatology. 2003;16:46–48.

Fotsis T, Pepper M, Adlercreutz H, et al. Genistein, a dietary-derived inhibitor of in vitro angiogenesis. Proceedings of the National Academy of Sciences USA. 1993;90:2690–2694.

Gyorgy P, Murata K, Ikehata H. Antioxidants isolated from fermented soybeans (tempeh). Nature. 1964;203:870–872.

Kang S, Chung JH, Lee JH, et al. Topical N-acetyl cysteine and genistein prevent ultraviolet-light-induced signaling that leads to photoaging in human skin in vivo. Journal of Investigative Dermatology. 2003;120:835–841.

Kapiotis S, Hermann M, Held I, et al. Genistein, the dietary-derived angiogenesis inhibitor, prevents LDL oxidation and protects endothelial cells from damage by atherogenic LDL. Arteriosclerosis, Thrombosis and Vascular Biology. 1997;17:2868–2874.

Kiguchi K, Constantinou A, Huberman E. Genistein induced cell differentiation and protein-linked DNA strand breakage in human melanoma cells. Cancer Communications. 1990;2:271–278.

Lambert JD, Hong J, Yang G, et al. Inhibition of carcinogenesis by polyphenols: evidence from laboratory investigations. American Journal of Clinical Nutrition. 2005;81(Suppl):284S-291S.

Lee EH, Cho SY, Kim SJ, et al. Ginsenoside F1 protects human HaCaT keratinocytes from ultraviolet-B induced apoptosis by maintaining constant levels of Bcl-2. Journal of Investigative Dermatology. 2003;121:607–613.

Li D, Yee JA, McGuire MH, Yan F. Soybean isoflavones reduce experimental metastasis in mice. Journal of Nutrition. 1999;29:1075–1078.

Manach C, Scalbert A, Morand D, et al. Polyphenols: food sources and bioavailability. American Journal of Clinical Nutrition. 2004;79:727–747.

Messina M, Barnes S. The role of soy products in reducing risk of cancer. Journal of the National Cancer Institute. 1991;83:541–546.

Monon LG, Kuttan R, Nail MG. Effect of isoflavone genistein and daidzein in the inhibition of lung metastasis in mice induced by B16F-10 melanoma cells. Nutrition and Cancer. 1998;30:74–77.

Okura A, Arakawa H, Oka H, Yoshinari T, Monden Y. Effect of genistein on topoisomerase activity and on the growth of [VAL 12] Ha-ras-transformed NIH 3T3 cells. Biochemical and Biophysical Research Communications. 1988;157:183–189.

Pinnell SR. Cutaneous photodamage, oxidative stress and topical antioxidant protection. Journal of the American Academy of Dermatology. 2003;48:1–19.

Pratt DE, Di Pietro C, Porter WL, Giffee JW. Phenolic antioxidants of soy protein hydrolyzates. Journal of Food Science. 1981;47:24–25.

Scalbert A, Williamson G. Dietary intake and bioavailability of polyphenols. Journal of Nutrition. 2000;130:2073S-2085S.

Tham DM. Potential health benefits of dietary phytoestrogens: a review of the clinical, epidemiological and mechanistic evidence. Journal of Clinical Endocrinology and Metabolism. 1998;83:2223–2235.

Wang Y, Yaping E, Zhang X, et al. Inhibition of ultraviolet B induced c-fos and c-jun expression by genistein through a protein tyrosine kinase-dependent pathway. Carcinogenesis. 1998;19:649–654.

Wei H, Bowen R, Zhang X, Lebwohl M. Isoflavone genistein inhibits the initiation and promotion of two-stage skin carcinogenesis. Carcinogenesis. 1998;19:1509–1514.

Wei H, Cai Q, Rhan R. Inhibition of Fenton reaction and UV light-induced oxidative DNA damage by soybean isoflavone genistein. Carcinogenesis. 1996;17:73–77.

Yamaguchi M, Goa YH. Genistein inhibits bone loss. Biochemical Pharmacology. 1998;55:71-76.

Yao-Ping L, You-Rong L, Jian-Guo X, et al. Topical applications of caffeine or (–)-epigallocatechin gallate (EGCG) inhibit carcinogenesis and selectively increase apoptosis in UVB-induced skin tumors in mice. Proceedings of the National Academy of Sciences USA. 2002;99:12455–12460.

Zwiller J, Sassone-Corsi P, Kakazu K, Boyton AL. Inhibition of PDGF-induced c-jun and c-fos expression by a tyrosine protein kinase inhibitor. Oncogene. 1991;6:219–221.

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