Efficacy and safety of innovative cosmeceuticals

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372 X.-H. Gao et al. (eg, actinic keratoses). 50 Large, blinded, controlled trials are needed to investigate the role of this novel retinoid in the treatment of photoaging. Genistein is a soybean isoflavone with diverse biologic activities. It substantially inhibits skin carcinogenesis and cutaneous aging induced by UV light in mice and photodamage in humans. The mechanisms of action involve protection of oxidatively and photodynamically damaged DNA, down-regulation of UV-B–activated signal transduction cascades, and antioxidant activities. 51 Clinical trials are required to further substantiate its clinical applications. A newly formulated vitamin C complex having 10% ascorbic acid (water soluble) and 7% tetrahexyldecyl ascorbate (lipid soluble) in an anhydrous polysilicone gel base was tested to one half of the face and the inactive polysilicone gel base to the opposite side. The effects were evaluated clinically and histologically. A statistically significant improvement of the vitamin C–treated side was seen in the decreased photoaging scores of the cheeks and the perioral area. Biopsies showed increased Grenz zone collagen, as well as increased staining for messenger RNA for type I collagen. No patients were found to have any evidence of irritation and inflammation during the 12-week trial. 52 Green tea polyphenol inhibits the activity of collagenase and increases collagen biosynthesis rate of human fibroblasts. Table 1 Examples of some cosmeceutical ingredients (in alphabetical order) Ingredients Purported action Source AHAs Exfoliation and improving circulation Fruit acids (glycolic acid, lactic acid, citric acid, titanic acid, pyruvic acid, maleic acid, etc) Allantoin Soothing the skin Comfrey root Aloe vera power Softening the skin Aloe vera α-Lipoic acid Free radical scavengers and antioxidant Plants and animals Arjunolic extract Antioxidant and anti-inflammation Terminalia arjuna β-Bisabolol Anti-inflammation, antibacteria Chamomile flower β-Hydroxy acids Antibacteria Plants Boswellic acids Anti-inflammation and antiaging Boswellia serrata Calendula oil Soothing, softening, and cell renewal Calendula officinalis Centella extracts Skin conditioning, increasing collagen production, Centella asiatica improving texture and integrity of skin Coenzyme Q10 (ubiquinone) Cellular antioxidants Naturally occurring in skin Coleus forskohlii oil Antimicrobial, aromatherapy/perfume C. forskohlii Coriander seed oil Anti-inflammation, skin lightening Coriandrum sativa Dry extract from yarrow Treatment of oily hair Achillea millefolium Essential fatty acids Smoothening, moisturizing, and protection Linoleic, linolenic, and arachidonic acids Furfuryladenine Improve hydration and texture of skin Plant growth hormone Ginkgo extracts Antioxidants, smoothing, rejuvenation of skin Ginkgo biloba Green tea extract Antiaging and antioxidants Green tea Horse chestnut extract Supporting blood circulation, wound healing, Aesculus hippocastanum and anti-inflammation Kinetin Free radical scavenger and antioxidant Plants and yeast Licorice extract Skin whitening, antioxidant, antimicrobial, Glycyrrhiza glabra and anti-inflammation Lupeol Antioxidant and skin conditioning Cratacva nurvula Neem oil limonoids Antimicrobial Azadirachta indica Oleanolic extract Antioxidant, improving texture and integrity of skin Olive leaf Panthenol Moisturizing and soothing skin Provitamin B 5 Pycnogenol Antiaging Grape seed Retinoids Smoothing, promoting cell renewal, and improving circulation of skin β-Carotene derivatives or synthetic compounds with similar mechanisms of action Rosemary extract Antioxidants, anti-inflammation Rosemarinus officinalis Sodium hyaluronate Lubricant, natural moisturizer Natural protein Tetrahydrocurcuminoides Antioxidant and antiaging Curcuma longa Turmeric oil Antibacterial and inflammation C. longa Ursolic acid Anti-inflammatory, collagen building up R. officinalis Vitamins A, E, and C Antioxidants Witch hazel Tones Hamamelis virginiana
Efficacy and safety of innovative cosmeceuticals It can also inhibit tyrosinase activity. It was interesting to note that after irradiation at 40 kGy by γ-ray, the abovementioned effects were all unregulated. 53 Green tea polyphenol or green tea could protect UV-induced DNA damage in a variety of cell types, including skin fibroblasts and keratinocytes. When green tea was taken orally, it also showed photoprotective effects manifested as low DNA damage of peripheral blood cells. 54,55 Orally taken green tea or green tea polyphenols have mild adverse effects, such as excess gas, upset stomach, nausea, heartburn, abdominal pain, dizziness, headache, and muscle pain. 56 Though it looks likely that green tea might be a suitable candidate for antiaging, so far, there have been no convincing reports on the evaluation of topical use of green tea or its derivatives on skin. It should be kept in mind that green tea polyphenols are highly unstable and easily oxidized in ambient environment. Formulary of green tea polyphenols as active ingredients in topicals, therefore, remains a challenge in the cosmeceutical industries. N-Furfuryladenine is a cytokinin growth factor that can be obtained from a variety of sources, such as plants, parts of animals, and even human urine. 57 In the presence of calcium, it could promote differentiation of human keratinocytes. 58 It could also inhibit oxidative and glycoxidative protein damage in vitro, and Fenton reaction– mediated oxidative damage to DNA. 59,60 Cosmetic products containing N(6)-F-furfuryladenine have been developed and marketed for a couple of years. A randomized, blinded, and controlled clinical trial is needed to evaluate its efficacy and safety. Conclusions The essence of innovative cosmeceuticals is their functional active ingredients. Hundreds of substances have been screened, synthesized, and tested (as exampled in Table 1), 2,16 and many have been included in commercially available products, for example, chamomile and soy. Prudent measures should be taken on clinical trials of cosmeceuticals because the interaction between skin and cosmeceuticals could be influenced by environmental factors as temperature, humidity, pollution, microbial, light, and so on. In addition, the desired functions of a cosmeceutical might require a coordinating action of multiple ingredients. Moreover, there are problematic skin conditions that might change the interactive pattern and outcome between cosmeceuticals and skin. Scientific clinical evaluation is a must for research, development, and application of cosmeceuticals. References 1. Kligman A. Cosmeceuticals: do we need a new category? In: Elsner P, Maiback H, editors. Cosmeceuticals. New York: Marcel Dekker; 2000. p. 1. 373 2. Dureja H, Kaushik D, Gupta M, et al. Cosmeceutical: an emerging concept. Indian J Pharmacol 2005;37:155-9. 3. Lee ES, Kim JH, Sungbin IM, et al. Application of computerized image analysis in pigmentary skin diseases. Int J Dermatol 2001;40:45-9. 4. Yoshimura K, Sato K, Aiba-Kojima E, et al. Repeated treatment protocols for melasma and acquired dermal melanocytosis. Dermatol Surg 2006;32:365-71. 5. Boissy RE, Visscher M, DeLong MA. DeoxyArbutin: a novel reversible tyrosinase inhibitor with effective in vivo skin lightening potency. Exp Dermatol 2005;14:601-8. 6. Chakraborty AK, Funasaka Y, Komoto M, et al. Effect of arbutin on melanogenic proteins in human melanocytes. Pigment Cell Res 1998; 11:206-12. 7. Maeda K, Fukuda M. Arbutin: mechanism of its depigmenting action in human melanocyte culture. J Pharmacol Exp Ther 1996;276:765-9. 8. Nakamura K, Yoshida M, Uchiwa H. Down-regulation of melanin synthesis by a biphenyl derivative and its mechanism. Pigment Cell Res 2003;16:494-500. 9. Usuki A, Ohashi A, Sato H, et al. The inhibitory effect of glycolic acid and lactic acid on melanin synthesis in melanoma cells. Exp Dermatol 2003;12(Suppl 2):43-50. 10. Galcia A, Fulton JE. The combination of glycolic acid and hydroquinone or kojic acid for the treatment of melasma and related conditions. Dermatol Surg 1996;22:443-7. 11. Moon KY, Ahn KS, Lee J, et al. Kojic acid, a potential inhibitor of NFkappaB activation in transfectant human HaCaT and SCC-13 cells. Arch Pharm Res 2001;24:307-11. 12. Nohynek GJ, Kirkland D, Marzin D, et al. An assessment of the genotoxicity and human health risk of topical use of kojic acid [5- hydroxy-2-(hydroxymethyl)-4H-pyran-4-one]. Food Chem Toxicol 2004;42:93-105. 13. Wan HM, Chen CC, Chang TS, et al. Combining induced mutation and protoplasting for strain improvement of Aspergillus oryzae for kojic acid production. Biotechnol Lett 2004;26:1163-6. 14. Kim DH, Hwang JS, Baek HS, et al. Development of 5-[(3- aminopropyl)phosphinooxy]-2-(hydroxymethyl)-4H-pyran-4-one as a novel whitening agent. Chem Pharm Bull (Tokyo) 2003;51:113-6. 15. Balina LM, Graupe K. The treatment of melasma. 20% azelaic acid versus 4% hydroquinone cream. Int J Dermatol 1991;30:893-5. 16. Draelos ZD. Cosmeceuticals: procedures in cosmetic dermatology. Philadelphia: Elsevier Saunders; 2005. p. 71-9. 17. Ortonne JP. Retinoid therapy of pigmentary disorders. Dermatol Ther 2006;19:280-8. 18. Gao XH, Chen HD, Kligman AM. Topical tretinoin for photoaging: the China experience. J Appl Cosmetol 1997;15:77-82. 19. Yoshimura M, Watanabe Y, Kasai K, et al. Inhibitory effect of an ellagic acid–rich pomegranate extract on tyrosinase activity and ultraviolet-induced pigmentation. Biosci Biotechnol Biochem 2005; 69:2368-73. 20. Yokota T, Nishio H, Kubota Y. The inhibitory effect of glabridin from licorice extracts on melanogenesis and inflammation. Pigment Cell Res 1998;11:355-61. 21. Nerya O, Vaya J, Musa R, et al. Glabrene and isoliquiritigenin as tyrosinase inhibitors from licorice roots. J Agric Food Chem 2003;51: 1201-7. 22. Kim HJ, Seo SH, Lee BG, et al. Identification of tyrosinase inhibitors from Glycyrrhiza uralensis. Planta Med 2005;71:785-7. 23. Kameyama K, Sakai C, Kondoh S, et al. Inhibitory effect of magnesium L-ascorbyl-2-phosphate (VC-PMG) on melanogenesis in vitro and in vivo. J Am Acad Dermatol 1996;34:29-33. 24. Curto EV, Kwong C, Hermersdorfer H, et al. Inhibitors of mammalian melanocyte tyrosinase: in vitro comparisons of alkyl esters of gentisic acid with other putative inhibitors. Biochem Pharmacol 1999;57: 663-72. 25. Kim DS, Park SH, Kwon SB, et al. Sphingosylphosphorylcholineinduced ERK activation inhibits melanin synthesis in human melanocytes. Pigment Cell Res 2006;19:146-53.
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