by Alison F. Stallings, MD [a], and Mary P. Lupo, MD, FAAD [b]

[a] Advanced Dermatology of Westchester, Tarrytown, New York; [b] Clinical Professor of Dermatology, Tulane Medical School, New Orleans, Louisiana

Abstract
Cosmeceuticals are the fastest growing sector of the cosmetic industry, and the future of antiaging cosmeceuticals in particular is very promising. Botanical extracts that support the health, texture, and integrity of the skin, hair, and nails are widely used in cosmetic formulations. They form the largest category of cosmeceutical additives found in the marketplace today due to the rising consumer interest and demand for natural products. Various plant extracts that formed the basis of medical treatments in ancient civilizations and many traditional cultures are still used today in cleansers, moisturizers, astringents, and many other skin care products. New botanical skin care treatments are emerging, presenting dermatologists and their patients the challenge of understanding the science behind these cosmeceuticals. Thus, dermatologists must have a working knowledge of these botanicals and keep up with how they evolve to provide optimal medical care and answer patient questions. The most popular botanicals commonly incorporated into skin care protocols are discussed.

(J Clin Aesthetic Derm. 2009;2(1):36–40)

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The cosmeceutical market is one of constant fluctuation depending upon consumer demand. Skin care companies are continuously pressured to release new, innovative products that promise to transform the appearance of aging skin overnight. Over the past decade, there has been fervent interest in products found in nature because of their perceived safety. Skin care products are often developed from plants. Many believe that if a product can be safely ingested, it will also be safe for topical application. In general, plant-derived, botanical, cosmeceutical products tend to be antioxidant in action since these organisms must thrive in constant direct ultraviolet (UV) light, the Earth’s most prolific manufacturer of free radicals. In this article, the authors review the most popular ingredients in this class and comment on their possible usefulness in skin care protocols.

Soy
Soy extract has positive research support for its antioxidant, antiproliferative, and anticarcinogenic activities. Topical application of soy has been used to reduce hyperpigmentation, enhance skin elasticity, control oil production, moisturize the skin, and delay hair regrowth.[1] Soy also has the potential to decrease photoaging of the skin and prevent skin cancers through the estrogen-type and antioxidant effects of its metabolites.[1]

The major components of soy are phospholipids, such as phosphatidylcholine and essential fatty acids. The minor components of soy include the most active compounds, such as isoflavones, saponins, essential amino acids, phytosterols, calcium, potassium, iron, and proteases soybean trypsin inhibitor (STI) and Bowman-Birk inhibitor (BBI). The various components of soy have a variety of beneficial effects making them useful additions to skin care products. The most potent isoflavones are the phytoestrogens known as genistein and daidzein. Genistein is a potent antioxidant that inhibits lipid peroxidation and chemical and ultraviolet light B (UVB)-induced carcinogenesis. Genistein was shown to significantly inhibit chemical, carcinogen-induced, reactive oxygen species; oxidative DNA damage; and proto-oncogene expression, as well as the initiation and promotion of skin carcinogenesis in mouse skin.[2] Topical estrogens have been shown to promote collagen synthesis and increase skin thickness, which may be beneficial for postmenopausal women who develop a thinner dermis and decreased collagen.[3] The small proteases STI and BBI appear to promote skin lightening and reduce unwanted facial and body hair in human clinical trials.[3,4] Beyond the depigmenting activity, STI, BBI, and soy milk were also found to prevent UV-induced pigmentation both in vitro and in vivo.[5] In addition, soy lipids, lecithins, and phytosterols are believed to restore barrier function and replenish moisture.

Beyond its moisturizing ability, soy appears to be a safe and effective treatment for postmenopausal women and for hyperpigmentation disorders (other than melasma, which is somewhat estrogen mediated). Although further research is necessary, the antioxidant and anticarcinogenic activities of soy and its isoflavones show a promising role for this botanical in the cosmeceutical industry. Soy has therefore become a popular addition to a wide variety of skin care products (see Table 1).

Teas: Green, Black, and White
Green tea extracts are among the fastest-growing herbal products. While there has been enormous growth in green tea consumption as a dietary supplement, the use of tea extracts in cosmeceutical formulations is also on the rise. The complex polyphenolic compounds in tea provide the same protective effect for the skin as for internal organs. They have been shown to modulate biochemical pathways that are important in cell proliferation, inflammatory responses, and responses of tumor promoters.[6] Green tea has been shown to have anti-inflammatory and antioxidant effects in both human and animal skin.

Since inflammation and oxidative stress appear to play a significant role in the aging process, green tea may also have antiaging effects by decreasing inflammation and scavenging free radicals. Researchers have found that the main active ingredient in green tea, epigallocatechin-3-gallate (EGCG), works well as an anti-inflammatory, antioxidant, and sunscreen. Topical green tea applied to human skin has been shown to provide a photoprotective effect, reduce the number of sunburn cells, protect epidermal Langerhans cells from UV damage, and reduce the DNA damage that formed after UV radiation.[7] Green tea polyphenols, when combined with traditional sunscreens, may have an additive or synergistic photoprotective effect. Green tea has also been found to decrease melanoma cells in tissue culture and squamous cell carcinoma cell formation in mice with topical and oral administration. Additionally, it improves wound healing by increasing keratinocyte cell differentiation and has been shown to inhibit Streptococcus species and Escherichia coli.[8]

Natural flavonoids, such as green or black tea polyphenols have been show to reduce UVB-induced erythema, tumorigenesis, and immunosuppression in mice.[9,10] White tea appears to be a more potent antioxidant than green tea. Black tea has a much lower content of catechins than green tea, but a higher content of other flavonoids, such as quercetin, theaflavin, and kaempferol. Black tea extracts applied before and after UV light challenge have been shown to decrease signs of cutaneous photodamage, carcinogenesis, and inflammation in human and mouse skin.[3]

Most cosmeceutical products containing tea extracts or phenols have not been tested in controlled clinical trials, but these substances have shown compelling evidence for antioxidant, anti-inflammatory, and anticarcinogenic activities. There are currently several products that contain green tea extract on the market (see Table 2). Unfortunately, the concentration of phenols is not standardized in these products; therefore, some products may have little-to-no therapeutic effect, making purchasing them a challenge for consumers. It is generally accepted that five-percent green tea extract or polyphenols in the 90-percent range is an effective concentration.

Chamomile
German chamomile, or Matricaria recutita, has been used throughout history as an herbal treatment for various skin conditions. It functions as an antimicrobial, antiallergic, anti-inflammatory, antioxidant, and analgesic and was approved by the German Commission E for inflammatory mucocutaneous diseases and wound and burn therapy.[3] The active constituents of chamomile include the terpenoids (bisoprolol, matricine, levomenol, chamazulene), flavonoids (apigenin, luteolin, rutin, quercetin), hydroxycoumarins, mono- and oligosaccharides, and mucilages. Chamazulene exhibits anti-inflammatory activity and promotes wound healing. Levomenol is an anti-inflammatory and natural moisturizing agent that has been found to diminish the signs of photodamage, reduce pruritus, and ameliorate skin texture and elasticity. In addition to reports of anti-inflammatory effects, chamomile is also purported to have some antioxidant properties, which have been identified through chemical assays.[11,12]

While chamomile is generally considered a safe product, there have been reports of contact dermatitis and conjunctivitis following topical application of chamomile products, and there is a potential risk of angioedema and anaphylaxis. Chamomile can also interact with warfarin, promoting an additive anticoagulant effect.

Clinical studies appear to support the traditional uses and therapeutic benefit of topical chamomile. This herb has been included in a wide variety of cosmetic products including soothing moisturizers and cleansers as well as color-enhancing hair products (see Table 3).

Caffeine
Caffeine, the chemical stimulant in coffee, tea, and some soft drinks, has demonstrated both anticarcinogenic and antioxidant properties. Initially, caffeine’s potential inhibitory role in cancer development was found through studying oral administration of black and green tea.[13] This study illustrated that the oral administration of caffeine alone and the addition of caffeine to decaffeinated teas showed inhibitory effects of UVB-induced carcinogenesis. Oral administration of caffeine has also been associated with in-vivo upregulation of tumor suppressor genes.[14]

Continued research revealed that topical application of caffeine inhibits carcinogenesis and promotes apoptosis in sunburn cells of hairless SKH-1, UVB-pretreated mice.[15] Researchers found that topical application of the tea constituents caffeine and (-)-epigallocatechin gallate (EGCG) decreased the number of nonmalignant and malignant skin tumors in SKH-1 hairless mice pretreated with UVB. While caffeine performed better than EGCG, both treatments resulted in elevated apoptosis in nonmalignant skin tumors and squamous cell carcinomas. The results suggest a need for further studies to determine whether topical applications of caffeine or EGCG can inhibit sunlight-induced skin cancer in humans. Further studies by the same authors found that topical application of caffeine sodium benzoate and caffeine have both a sunscreen effect and enhance UVB-induced apoptosis and may be good agents for inhibiting the formation of sunlight-induced skin cancer.[16]

These studies present a potential use for caffeine in formulations used to decrease the risk of skin cancer formation after cutaneous damage from UV exposure. More studies need to be done to further examine caffeine’s antioxidant potential. The above findings have prompted many manufacturers to add this popular agent to various cosmeceutical products on the market today (see Table 4).

Coffeeberry
Coffeeberry, harvested from the fruit of the coffee plant Coffea arabica, is considered to be one of the richest sources of antioxidants and is well known for its skin-rejuvenation properties. Coffeeberry contains potent polyphenols including chlorogenic acid, ferrulic acid, quinic acid, and condensed proanthocyanidins. The dermatologic application of CoffeeBerry® (J&J Technologies LC) extract was first recognized at the American Academy of Dermatology’s Annual Meeting in February 2007. The first product to enter the market with CoffeeBerry as the basic ingredient is RevaléSkin (Stiefel Laboratories, Inc., Coral Gables, Florida) (see Table 5).

According to Stiefel Laboratories, Inc., CoffeeBerry has demonstrated high antioxidant properties, outperforming green tea extract and vitamins C and E. Proprietary research from the manufacturer has also shown that the use of the RevaléSkin CoffeeBerry skin care system consisting of 0.1% CoffeeBerry cleanser and 1% day and night creams showed statistically significant improvement in fine lines, wrinkles, pigmentation, and overall appearance when compared to vehicle. In addition to the evidence of safety and efficacy provided by the randomized, double-blind trials, further support comes from positive pathologic and in-vitro studies showing enhanced collagen production by fibroblasts. Studies are currently in progress to evaluate the use of the CoffeeBerry skin care system in conjunction with retinoids and intense pulsed-light treatments.[17] More clinical studies need to be performed to fully assess the topical preparations containing CoffeeBerry extract, but polyphenols have already demonstrated efficacy in photoaging and skin cancer prevention.

Conclusion
The inclusion of botanicals in skin care products is becoming ever more popular. Potential antioxidant and anti-inflammatory benefits may prove beneficial for a number of conditions that dermatologists routinely treat, such as rosacea, photoaging, and skin cancer. The published effectiveness of prescription retinoids is well known, but equally well known is the irritation and redness often caused by the initiation of therapy. Botanicals may hold the promise of utility to reduce such inflammation. This is one of the best and most practical reasons to include botanicals in skin care protocols. Dermatologists should be aware of these products and be able to discuss their uses and potential benefits with their patients.

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