The Pomegranate is a powerful antioxidant that can protect the skin and the body from disease.

Of natural remedies, the pomegranate is by far one of the oldest known to man. In fact, the pomegranate tops the list when it comes to ancient healing benefits.

A native plant of Northern Africa, pomegranate (Punica Granatum L) was written about in 1552 B.C. in the Egyptian Ebers Papyrus, which is one of the oldest and most important medical documents yet recovered.

The Ebers Papyrus contains more than 700 remedies for treating disease; pomegranate is noted as one of the most popular ingredients. For example, physicians in Greece prescribed pomegranate juice as a remedy with multiple activities. It acted as an anti-inflammatory and as a potent anthelmintic, which could expel or destroy intestinal worms. It also was used to treat chronic diarrhea, dysentery, viruses and digestive problems.

In Mediterranean and Caucasian folk medicine, pomegranate extract helps strengthen the human capillary system. It also is used as an anti-asthma agent and for tonsillitis and bronchitis.

Meeting Environmental Challenges

While history teaches us that this unassuming fruit possesses valuable healing powers, the pomegranate shows incredible potential to meet our body’s needs in the face of increasing environmental challenges. Indeed, studies I’ve conducted confirm the healing potential of the pomegranate on the external and internal level, offering exciting applications for health and longevity.

Each day, the skin—the body’s largest organ—is bombarded with environmental assailants. In fact, the cells of the body sustain thousands of free radical hits. Moreover, ever increasing external aggressors, such as pollution, smoke and ultraviolet radiation from the sun, trigger the release of additional inflammatory mediators. These further break down collagen and damage cell barriers. This increased internal damage can produce wrinkles and hyperpigmentation. But perhaps more importantly, this internal damage contributes to the formation of cancerous cells.

Since my early days as a dermatologist, I’ve been studying the ability of various antioxidants, such as vitamin C, coenzyme Q10, alpha lipoic acid, grape seed extract, vitamin E and herb extracts, such as burdock root, echinacea and yellow dock root, to repair and protect the skin against such damage. However, I found the most potent antioxidant power to date is ellagic acid contained in the pomegranate.

Ellagic acid is a powerful free radical scavenger and extremely effective in increasing the body’s own built-in antioxidant glutathione. This, in turn, helps protect the DNA in cells from free radical damage. Glutathione also is essential in helping the body recycle hormones, such as estrogen, which also protects skin cells.

Polyphenols, such as ellagic acid, also inhibit the formation of harmful enzymes that cause cells to grow out of control. This is important in preventing cancer because out-of-control cell division is a hallmark of this disease. By inhibiting specific enzymes, ellagic acid and other polyphenols regulate cell turnover and give the cell time to divide normally and form completely. Ellagic acid also is thought to strengthen the cell membrane, making it less susceptible to free radical damage. It also prevents water loss from the cell. This, in turn, helps deter the aging process.

I first began studying the effects of pomegranate extract in the early 1990s. After this research was published in Cosmetic Dermatology, pomegranate extract began to pique the interest of university scientists.

Protecting the Skin

Intrigued by the powerful benefits of pomegranate extract, I theorized that it could play a significant role in protecting the skin from all types of environmental damage, specifically ultraviolet rays. To prove this theory, I initiated an independent pilot study to determine the effect of pomegranate extract in improving the sun protection factor of sunscreens.

In 1999, I asked an independent laboratory to test the effect of pomegranate extract on the sun protection factor of volunteers. Thirty-two subjects (male and female, ages 18 to 60, with fair to medium skin types) used pomegranate extract orally and topically. First, their minimal erythema dose (MED) was tested. Next, they applied four formulas (standard SPF 4 and SPF 8 lotions with and without pomegranate extract) and assessed for SPF. Subjects then tested pomegranate extract daily for five days under supervision. At the endpoint, subjects were tested again for SPF. Adding pomegranate extract boosted the SPF of the sunscreen formula by 20 percent. Over and above that, ingesting a 15 mg tablet of standardized pomegranate extract provided an additional 25 percent improvement in the SPF.

Research Findings

In October 2000, the Journal of Agri-cultural Food Chemistry covered research by a team from South Dakota University. They reported that when applied topically on mice, pomegranate oil inhibited papilloma incidence and activity.

In the fall of 2003, researchers at the University of Wisconsin evaluated pomegranate’s anti-skin tumor effects. They did so by comparing the topical application of pomegranate extract on neonatal mice against TPA-induced markers (12-0-tetradecanoylphorbol-13-acetate), a strong promoter of chemically induced skin cancer. Applying pomegranate extract onto the skin of neonatal mice 30 minutes before the TPA application significantly inhibited TPA-mediated increases in skin edema and hyperplasia, researchers found.

They also tested the pomegranate extract on TPA-induced skin tumor promotion. The animals pretreated with pomegranate extract showed substantially reduced tumor incidence and lower tumor body burden. In the TPA-treated group, all mice developed tumors at 16 weeks, while only 30 percent of the mice treated with pomegranate extract exhibited tumors at that point.

Perhaps the most extraordinary result of these studies is the discovery of pomegranate’s age-proofing capabilities and healing benefits. When taken orally, this ingredient boosts the SPF rating of topical sunscreens so that the same SPF protection levels are maintained, using fewer chemicals and more antioxidants.

Indeed, the protective and healing properties of the pomegranate are extremely important today, as the rate of skin cancer is growing increasingly faster than any other cancer among Western countries. However, applying sunscreen alone isn’t enough, and much of our challenge lies in education. For instance, the SPF of a sunscreen doesn’t tell the entire story. An effective product should provide:

• Full-spectrum sun protection to block UVA and UVB rays.
• Antioxidants, such as pomegranate, green tea, vitamin C, grape seed extract and bioflavonoids to neutralize damaging free radicals.
• Anti-inflammatory agents, such as licorice extract, zinc or chamomile extract, to soothe and prevent redness.
• Hydrating ingredients, such as sodium PCA, hyaluronic acid and plant-based lipids, to boost topical hydration in the cells.

Fortunately, I’ve noticed an ever-increasing consumer awareness of pomegranates, both as an ingredient in topical antioxidant products and as a key ingredient in many food and juice products.

Perhaps the most exciting development is the mainstream understanding and demand for antioxidants and SPF in topical skin care products. Today’s average consumer is well-versed about the effects of environmental damage, both from a cosmetic and wellness perspective. As a result, ingredients such as pomegranate are becoming increasingly integral components of skin care, and SPF has been widely included into cosmetic products. Moreover, consumers are adopting proactive paradigms about their bodies and overall wellness, becoming savvy about the benefits of antioxidants.

As health care professionals continue to research and develop the potential of this ancient fruit, we enter into an exciting period. Pomegranate offers consumers the cosmetic benefits of beautiful, wrinkle-free skin while providing valuable, life-saving protection against environmental damage. However, further research about pomegranate extract is necessary to fully realize the healing and protective properties of this medicinal fruit.

Pomegranate Power

Pomegranate contains polyphenols, tannins and anthocyanins, all of which are antioxidants. Pomegranate juice, in fact, contains higher levels of antioxidants than most other fruit juices, red wine or green tea. The following studies show the fruit’s potential in fighting disease. However, most of these studies are small, so more research is needed.

Ischemic heart disease; 2005 study published in the American Journal of the College of Cardiologists examined the effect of pomegranate juice on patients with ischemic heart disease. Forty-five patients drank 8 ounces of the juice or placebo for three months. Blood flow to the heart before and after exercise was measured at zero and three months. In patients drinking pomegranate juice, oxygen deficiency to the heart during exercise was significantly lowered compared to placebo. This suggests increased blood flow to the heart.

Erectile dysfunction; a study published in the Journal of Urology examined the effects of long-term intake of pomegranate juice on erectile dysfunction in an animal model. The results suggest that oxidative stress is a contributing factor in erectile dysfunction. Therefore, pomegranate juice may provide its benefit through an antioxidant mechanism.

Alzheimer’s disease; a recent study, published in Neurobiology of Disease, shows that pomegranate juice could halve the buildup of beta-amyloid deposits, which are associated with an increase in brain cell damage and death from oxidative stress. In an animal model, researchers at Loma Linda University in California found that the pomegranate juice-supplemented groups had 50 percent fewer deposits than the nonsupplemented group. While far more research needs to be done, this work suggests that the polyphenols in pomegranate juice may protect against oxidative stress.

Cholesterol; preliminary evidence suggests that drinking concentrated pomegranate juice may reduce cholesterol. Israeli researchers published their findings in the June 2004 issue of Clinical Nutrition. Drinking a glass of pomegranate juice a day for one year reduced blood pressure in subjects, particularly systolic pressure, and slowed LDL cholesterol oxidation.

The Future of Antioxidants

The role of antioxidants in both anti-aging and protective topical products has become a hot-button topic. Amongst the aging baby boomer generation, topical antioxidant products are increasingly in demand, both to reverse damage accumulated over years of exposure to the sun, dehydration, and environmental assailants and to protect skin from the harmful effects of such environmental pollution. I have also noticed a preventative trend resonating in Gen X and Gen Y’ers, who are adopting anti-aging skincare regimens (as early as 20 years of age), in an attempt to thwart signs of aging and protect skin from environmental damage before the tell-tale signs of aging emerge.

Perhaps the most exciting development of all is the mainstream understanding and demand for antioxidants and SPF in topical skincare products. Today’s average consumer is well versed and educated as to the effects of environmental damage, both from a cosmetic and a wellness perspective. As a result, ingredients such as Vitamin C and Pomegranate are becoming increasingly integral components of skincare and SPF has been widely included into cosmetic products. More and more, customers are adopting proactive paradigms about their bodies and overall wellness, becoming savvy about the benefits of Vitamin C and Pomegranate. Consumer knowledge and education translates directly to the esthetician and spa professional, as the demand for such antioxidant rich treatments escalates by the day.

As skincare professionals continue to research and develop advanced antioxidant technologies, we enter into an exciting period where dermatologists and estheticians can offer the consumer the cosmetic effects of beautiful, wrinkle free skin while providing valuable, life saving protection against environmental damage.

By Howard Murad, MD

Howard Murad, MD, is a board-certified dermatologist, pharmacist, researcher and associate clinical professor of medicine (dermatology) at the Geffen School of Medicine, UCLA. Dr. Murad oversees the Murad Inclusive Health® Center, the Murad Medical Spa, Murad Medical Group and the Murad Research Laboratory, all based in Southern California. He is an active member of the American Academy of Dermatology, the American Society of Dermatologic Surgery, the American Medical Association, the Pacific Dermatology Society, the Noah Worcester Society and the American College of Nutrition. He holds 17 patents, with several more pending. A successful author, Dr. Murad has written two books and published nearly 100 articles on topical ingredients, as well as internal and emotional health and their relationship to the skin.

Disclosure: Dr. Murad indicates that he has an ownership position in a health care-related company whose products are referred to in this article. He also holds a patent for a product or category of products referred to in this article. In addition, he has an ongoing relationship with a health care-related company whose products or category of products is referred to in this article.

Dr. Murad is a researcher, Board-Certified Dermatologist, pharmacist, Associate Clinical Professor of Dermatology at the David Geffen School of Medicine at UCLA and CEO of Murad, Inc.

Global Organic New Product Launches Outpace Naturals in Skin Care

Organics have accelerated past naturals in Mintel data on beauty launches but the market research firm does not expect the trend to continue.

Organic growth

Of 15,000 ‘all natural’ and organic products released so far this year around two thirds were organic, according to data drawn from Mintel’s Global New Products Database (GNPD).

Charting the global figures over the past two years indicates that ‘all natural’ launches have tailed off while the number of organic products hitting the market has continued to increase sharply.

Starting from a similar level at the beginning of 2006, organics has accelerated past ‘all natural’ so that they now take a two thirds share of the market niche.

Naturals expected to win

Despite what the data suggests, Mintel expects ‘all natural’ to win out in the end.

Beauty analyst Nica Lewis told CosmeticsDesign.com that the growth of the organic market will be hampered by supply issues.

She said: “Companies are already buying up all the available supplies of certain ingredients making it harder for others to expand in the long run.”

Consumer demand for organic cosmetics continues to be strong but Lewis said the free-from trend will perhaps trump the organic movement.

Consumers are determined to avoid certain ingredients such as parabens and may opt for free-from products rather than fully organic alternatives.

Lewis said the organic movement also faces other challenges such as the harmonization of standards.

Currently, the proliferation of organic certification bodies is causing confusion that could have an impact on sales.

“Consumers have a much clearer idea of what an ‘all natural’ cosmetic product is than an organic one,” added Lewis.

Related to this is the issue of strengthening standards that is set to continue especially in the US where products are often marketed as organic despite having little organic content.

Tougher standards and regulations will make it harder and more expensive for many companies to use the organic claim. Lewis said this will put significant downward on the number of organic beauty launches in the coming years.

Natural or Organic – an ongoing debate Where is the standardization and safety in the cosmetics arena?

The Cosmetic industry is aware that consumers are trending toward inner and outer well-being, which is impacting their spending behavior and decisions, from the foods they eat to the cosmetics they use. There is a lot of confusion in the personal care industry over which ingredients are healthy for the skin.

The term “natural” is not regulated by the FDA, which basically leaves each vendor to set its own standards for what the term means. Some brands marketed as “natural” are formulated with high concentrations of plant-based and naturally derived ingredients, and fewer parabens, sodium lauryl sulfate, phthalates, petrochemicals, and synthetic fragrances or dyes. We are seeing more natural preservatives, emulsifiers, etc. Current labeling standards are open to interpretation and allow products to be called “natural” even if only a small percentage of ingredients could technically fall under that umbrella.

The definition of “organic” refers to products containing ingredients grown and processed without the use of pesticides, herbicides, or insecticides. ‘Organic’ describes how it was grown. These regulations fall under the US Department of Agriculture (USDA)’s standards for organic foods. Since 2006, the USDA began allowing beauty companies to use its USDA organic seal on products that meet its requirements for food.
The requirements for labeling a product as “natural” are far less defined than the requirements for labeling a product as “organic.” Marketers seeking to create impact with performance are using natural ingredients as a key element of their marketing strategy in cosmetics and toiletries with a noticeable shortage of clinical data that actually proves that these products are effective. Some brands are picking up on this selling point by incorporating a “chemical-free” or “preservative-free” message into their product labeling. Differentiating between the levels of quality within the natural sector is proving to be a great challenge for skin care experts, physicians, and retailers alike.

The need to create a common definition and logo for natural and organic products is a recurring theme during conferences in Europe and USA. Many participants were surprised to discover that organic-certified products in France have to contain just 10 percent of organic ingredients to earn the “bio” label domestically. Meanwhile, natural cosmetics, called “eco” in France, only need to contain 5 percent of organic ingredients. The requirements also vary widely from country to country for natural and organic cosmetics.
Beauty retailer Sephora, CA, now categorizes products it sells as “natural” or “organic.” Estee Lauder-owned Origins has added a “certified organic” range to keep up with pressure from new competitors. Some brands are picking up on this selling point by incorporating a “chemical-free” or “preservative-free” message into their product labeling.

TARGET STORES TO LAUNCH NINE NATURAL / ORGANIC BRANDS

Retailer “Target” unveiled this month a new line of certified natural and Organic skin care products developed exclusively for multicultural skin types. On the mass-market level, Aveeno is one of the most successful brands in the natural segment, with its skin care range based on Johnson & Johnson’s patented active natural ingredient Feverfew, as well as soy, oats, and shiitake mushroom. Provencale beauty rang+e–Occitane, is certified organic by ECOCERT.

European Union (EU) has more strin gent and protective laws for cosmetics than USA does. If Ecocert is approved by the USDA, then certification by Ecocert is just as good as certification provided by the USDA.

In USA the regulation of cosmetics is woefully outdated. FDA needs to know who is making personal care products, and what products they are making, as a basic first step to protecting the public health. Ingredients and products are not subject to FDA premarket approval authority, with the exception of color additives. FDA has virtually no power to perform even the most rudimentary functions needed to ensure the safety of an estimated $35 billion of personal care products purchased by consumers annually The safety of personal care product ingredients is evaluated through a voluntary industry program known as the Cosmetic Industry Review (CIR) process. In the absence of the CIR program, there would be no systematic examination of the safety of individual cosmetic ingredients.

The recent draft legislation of FDA globalization Act of 2008 is a major step by FDA to update the Federal Food, drug and Cosmetic Act. It requires any facility engaged in manufacturing, processing packaging or holding of cosmetics in the US or for import to the US shall be required to register (and pay registration fees) under subsections (a) and (b) of section 604 of the Federal Food, drug and Cosmetic Act. The act also requires adverse-event reporting for cosmetics.

DEVELOPING “ALL NATURAL” PERSONAL CARE PRODUCTS: AN OVERVIEW OF ANTIMICROBIAL AND PRESERVATIVE OPTIONS

The need to control microbial activity is inherent in two major facets of personal care, namely, antimicrobial care wherein the product helps to retard the growth of topical pathogens or eliminates them, and preservatives that retard the growth of microbes in personal care product formulations.

In recent years, there has been increased dialogue related to natural antimicrobials as topical actives and preservatives in the personal care industry. Synthetic compounds long accepted as effective in controlling microbial growth have come under scientific and regulatory scrutiny. These efforts are mainly driven by safety and environmental concerns, and the increased incidence of antibiotic resistant microbial strains. Natural alternatives derived from botanicals are therefore being explored by researchers across the world.

TOPICAL ANTIMICROBIALS: AN INTRODUCTION

Like all biological materials, the skin harbors resident microflora. Under certain conditions and in some groups of people, the skin microflora grows invasively and triggers pathological processes resulting in acne, infections and skin eruptions.

Invasive growth of certain microorganisms causes scalp infections and infections in the oral cavity, as well. Certain microorganisms found in the skin, scalp and nails may also generate malodor and irritation, affecting general health and well being.

Antimicrobials find functional applications in cleansing formulations, deodorants and topical protectant formulations.

• Examples of skin pathogens include Propionibacterium acnes a microorganism associated with acne and other skin infections, Staphylococcus aureus a bacterial strain found in infected wounds and skin eruptions including acne, Staphylococcus epidermidis a bacterial strain occurring in a variety of opportunistic bacterial skin infections and in acne, corynebacteria and micrococci that cause body odor. Athlete’s foot (Tinea pedis) and onychomycosis (nail fungus) are other infections associated with the skin and nails.

• Examples of oral cavity pathogens include Streptococcus mutans, a bacterial strain associated with the progression of dental caries, Examples of scalp pathogens include Pitysporum ovale (Malassezia furfur, yeast strain associated with dandruff). Microorganisms also affect dental health. Gum disease involves bacterial growth and production of metabolic substances that gradually destroy the tissue surrounding and supporting the teeth. These bacteria grow and attack the tissues causing “gingivitis” characterized by inflamed gums that bleed easily. If left untreated the condition progresses to “periodontal disease” wherein there is severe

inflammation, bone damage and tooth loss. The causative bacteria reside in plaque, a deposit that forms on the base of the teeth and hardens to form “tartar”. Poor oral hygiene is the major cause of gum disease. Lifestyle, nutrition and the ageing affect the immune response, and increase the risk of gum disease. Antimicrobials target oral pathogens such as Streptococcus mutans, while anti-inflammatory and wound healing extracts offer support to healthy gums and teeth.

• Antibiotic resistant strains of microorganisms arise from non‐judicious use of conventional antibiotics. There is therefore a need for natural products that effectively inhibit the growth of microorganisms. Multifunctionality is an additional advantage of natural extracts. Several of them offer anti‐inflammatory, immunological and wound healing support as well.

• In the last few years, a number of laboratory studies have revealed the efficacy of plant extracts and phytochemicals as antimicrobials. These properties are attributed to the presence of secondary metabolites such as phenolics in essential oils and tannins in herbal extracts.

• Some examples of classes of natural materials that afford antimicrobial protection include essential oils such as tea tree oil, rosemary oil, turmeric oil; plant extracts such as rosemary extract, sage extract, lemon balm extract, green tea extract, Kaempferia galanga extract, Neem leaf extract and oil, and isolated phytochemicals such as cinnamates, benzoates, eugenol.

NATURAL ANTIMICROBIALS: ILLUSTRATIVE EXAMPLES COLEUS OIL

(INCI: COLEUS FORSKOHLII ROOT OIL)

Coleus oil is an essential oil extracted from the roots of Coleus forskohlii a plant from the Natural Order Labiatae (Lamiaceae), a family of mints and lavenders. This species is a perennial herb with fleshy, fibrous roots that grows wild in the warm sub‐tropical temperate areas in South Asia. The roots are eaten as a condiment or pickle in India. In recent years Coleus forskohlii has gained pharmacological importance as the only known plant source of the biologically active compound, forskolin. (1) A coleus oil is an useful byproduct of forskolin extraction.  The newly discovered antimicrobial properties of the oil (of specific composition obtained using a proprietary extraction process) render it useful in topical preparations. (2) Compounds such as 3‐decanone (about 7%), bornyl acetate (about 15%), sesquiterpene hydrocarbons and sesquiterpene alcohols in major concentrations imparts unique pleasing spicy notes to the essential oil. β‐sesquiphellandrene (about 13%) and γ‐eudesmol (12.5%) were identified in experimental studies on the oil. (3) In laboratory studies, Coleus oil was found to more effectively inhibit the growth of skin pathogens including Propionbacterium acnes (associated with acne), Staphylococcus aureus (a bacterial strain found in infected wounds and skin eruptions including acne), Staphylococcus epidermidis a bacterial strain occurring in a variety of opportunistic bacterial skin infections and in acne, than the well known tea tree oil. Additionally, Coleus oil was found to inhibit the yeast culture Candida albicans more effectively than tea tree oil. (2) The extract is safe to use in cosmetic formulations, it does not irritate the skin and its pleasant woody aroma blends with cosmetics.

KAEMPFERIA GALANGA (INCI: KAEMPFERIA GALANGA ROOT EXTRACT)

Kaempferia galanga (Lesser galangal, kencur), and Alpinia galanga (greater galangal) from the Zingiberaceae family are commonly used as spice ingredients and medicinal herbs in South‐east Asia and are valued traditionally for their protective topical effects when applied as pastes. Kaempferia galanga rhizome contains about 1.5 to 2% essential oil, whose main components are ethyl cinnamate (25%), ethyl‐p‐methoxycinnamate (30%) and p‐methoxycinnamic acid. Kaempferia galanga is a good natural source of a biologically active ester compound ethyl p‐methoxycinnamate.  (1) The antifungal action of ethyl‐p‐methoxycinnamate is reported in literature. (5)  In laboratory studies, the fraction of the extract rich in ethyl p‐methoxycinnamate was found to effectively inhibit the growth of Propionibacterium acnes, producing significant zones of inhibition at concentrations even as low as 0.5%. (6)

TURMERIC OIL (INCI: CURCUMA LONGA) CURCUMA LONGA ROOTS, THE SOURCE OF TURMERIC OIL

Turmeric oil is obtained by steam distillation or solvent extraction of the powdered rhizome of species of the genus Curcuma (Family: Zingiberaceae). Of these species, Curcuma longa is the most well known. Curcuma longa yields 0.3‐7.2% (usually 4‐5%) of turmeric oil following steam distillation. The chief constituents of the essential oil are In India, turmeric is known for its cosmetic and wound healing properties since ancient times. The essential oil has been used as a perfume component and studies have shown that it furnishes antibacterial/antifungal (8‐11), anti‐inflammatory, insect-repellant activities and is effective in the treatment of scabies.

OLEUROPEIN: INCI: OLEA EUROPAEA (OLIVE LEAF EXTRACT) OLIVE LEAVES, THE SOURCE OF OLEUROPEIN

Oleuropein is a polyphenolic compound found in plants belonging to the Oleaceae family, of which the olive tree is a member. The olive tree (Olea europaea) was known in biblical times as the “Tree of Life”.

Oleuropein is the major phenolic constituent extracted from olive leaf, (constituting about 19% (w/w)) and from the polar fraction of virgin olive oil. Oleuropein is reported to be hydrolyzed to another biologically active compound, hydroxytyrosol, in vivo. A variety of anitimicrobial actions of oleuropein and its associated compounds have been demonstrated in vitro. The inhibitory action of oleuropein against the growth and toxin production of Staphylococcus aureus, Bacillis cerus, Pseudomonas syringae and several other bacterial strains (by oleuropein or its hydrolysis products) in vitro, is documented. For example, the presence of low concentrations (0.1% w/v) of Oleuropein delayed the growth of Staphylococcus aureus in nutrient media, while higher concentrations (0.4‐0.6% w/v) inhibited growth completely. Concentrations of oleuropein greater than 0.2% w/v inhibited growth and enterotoxin production in both types of media.

NEEM OIL AND NEEM LEAVES EXTRACT (INCI: MELIA AZADIRACHTA)

The Neem tree is traditionally labeled as “The Village Pharmacy” on account of its multifaceted healthful properties. Its properties range from immunomodulatory and anti‐inflammatory effects to antimicrobial and pesticidal attributes. The leaves and seeds of Neem yield limonoids with wide biological applications. These have antibacterial, antiviral, insect repellant, anti‐protozoal and anti‐helmenthic properties.

The seed oil at concentration of 0.3% on agar plates were active against Stahylococcus aureus and at 0.4% was active against Salmonella typhosa. The seed oil at concentration of 3% on agar plate, was active against E.coli and Proteus species, a concentration of 6.0% was active against Klebsiella pneumoniae. Methanol and Butyl‐methyl‐ether extracts showed antifungal activity against the following strains of fungi including Epidermaphyton floccosum, Microsporum canis, Microsporum gypseum, Trichophyton concentricum, Trichophyton entagrophytes, Trichophyton rubrum and Trichophyton violaceum.(15)

A recent study determined the efficacy of a mucoadhesive dental gel containing Azadirachta indica leaf extract (25 mg/g). using commercially available chlorhexidine gluconate (0.2% w/v) mouthwash as positive control. The results of the study suggested that the dental gel containing neem extract significantly reduced plaque index and bacterial count as compared to the control group. (16)

GREEN TEA EXTRACT: (INCI: CAMELLIA SINENSIS LEAF EXTRACT)

The catechins in green tea were found to inhibit Staphylococci and Yersinia entero‐colitica. Green tea extracts may make strains of drug‐resistant bacteria more sensitive to penicillin. In vitro studies on particular antibiotic resistant strains of Staphylococcus aureus revealed that addition of green tea extract induced reversal of penicillin resistance. It was found that epicatechin gallate, markedly lowered the minimum inhibitory concentration (MIC) of oxacillin and other beta‐lactams. (17,18) Extracts of green tea were found to strongly inhibit Escherichia coli, Streptococcus salivarius and Streptococcus mutans, microorganisms found in the saliva and teeth of people suffering from dental caries. (19) Green tea in combination with the synthetic antioxidant Oleuropein had bactericidal effects against a broad spectrum of gram‐positive and gram‐negative bacteria, but no effect was observed against yeast. (12) Antiviral properties (13) are also reported in vitro and in vivo. Although the precise mechanism of antimicrobial action has as yet to be elucidated,(12,14) oleuropein and related compounds appear to have surface‐active properties that interfere with microbial cell membranes. Oleuropein could also interfere with the synthesis of amino acids that are crucial to viral replication and in the case of retroviruses, neutralize the production of reverse transcriptase and protease. Additionally, oleuropei butylated hydroxyanisole (BHA) reduced the hydrophobicity of S. mutans and greatly inhibited.

NATURAL PRESERVATIVES

A preservative is essentially a chemical agent that will destroy microorganisms or prevent their growth in finished formulations. There is ample scope for microbial contamination at the end user level. It is therefore important that the cosmetic product be protected by a suitable preservative system to ensure safety in use and adequate shelf life.

Factors such as water activity and pH of the formulation, and the solubility and stability of the preservative in the base composition are factors that determine preservative efficacy.

Additives such as glycerol, butylene glycol, salt (sodium chloride), sugars, soluble starches, dextrin, xanthan gum and others absorb water thereby lowering the water activity of the composition.

Parallels in the list of natural actives include glucans, mannans and other polysaccharides extracted from commonly used culinary materials such as tamarind seed and fenugreek.

In the area of chemical preservatives that stop or inhibit microbial growth, common classes of chemicals used include acids, aromatic alcohols, N‐methylol containing compounds, halogenated compounds, isothiazolinones, quaternary nitrogen compounds, and (1,2) idols. A number of phytochemicals found in natural sources resemble these compounds in chemical structure and are natural preservatives. These classes of phytochemicals include essential oil constituents (such as eugenol, thymol, carvacrol, terpenoid compounds), flavonoids, phenolic compounds, tannins and alkaloids. Some of these extracts when combined.

Although no single natural extract has been found to be comparable in efficacy to conventionally used preservatives such as parabens, combinations of naturals with synergistic activity have been identified. Such extracts could offer protection against invasive growth of bacteria and fungi.

Parabens for example, are poorly water soluble and their action is strongest against gram positive bacteria and fungi and weakest against gram negative bacteria. Combinations of synthetic preservatives are therefore used in formulations and the safety and global regulatory acceptance of effective levels of such combinations is sometimes a problem. It is here that combinations of natural extracts may be useful.

Very often such extracts also offer antioxidant action, with beneficial effects on product shelf life. One example is a proprietary natural extract of yellow curcuminoids from Curcuma longa (turmeric) roots (3) and a colorless derivative Tetrahydrocurcuminoids (INCI:Tetrahydrodifuruloylmethane, Tetrahydrodemethoxydiferulolylmethane, Tetrahydrobisdemethoxydiferuloylmethane), that were found to offer more effective antioxidant protection than the conventionally used synthetic antioxidant butylated hydroxytoluene (BHT).(21)

Another example is resveratrol (Resvenox®4) which offers antimicrobial and antioxidant benefits. Resveratrol is found in widely varying amounts in grapes (primarily the skins), raspberries, mulberries, blue berries, bilberries, cranberries, peanuts, scots pine, eastern white pine, and the roots and stalks of giant knotweed and Japanese knotweed (Polygonum cuspidatum). It has antibacterial and antifungal properties. (22)

CONCLUSIONS

An overview of some of the natural alternatives to synthetic preservatives and antimicrobial functional ingredients in cosmetics is presented here. Synergistic blends of these materials would be functional, and simultaneously benefit the “all natural” image of personal care products.

Fighting the Signs of Aging

In the war on aging skin, we now have a new generation of cosmeceuticals that offers unprecedented clinical benefits. These advanced technologies are based on breakthrough scientific discoveries and peer-reviewed science. Ultra-potent antioxidants, stem cell modulators and antisense DNA technologies are advancing our clinical understanding of the intrinsic and extrinsic aging processes, offering targeted strategies for slowing down and/or reversing the signs of aging.

Before discussing these new generations of products, let’s first review the aging process, which has intrinsic and extrinsic bases in humans. These two clinically, bio­logically independent and distinct processes affect skin structure and function.

Intrinsic or innate aging is a natural process that occurs from slow, but progressive and irreversible tissue degeneration. Telomere shortening, metabolic oxidative damage and free reactive oxygen species play a major role in the innate aging process.¹ Based on unique genetic factors, intrinsic aging affects everyone at different rates.

On a histological level, intrinsic aging is characterized by decreased collagen synthesis, degeneration of elastic fiber networks and loss of hydration. Clinically, fine wrinkling of the skin, loss of skin tone, skin laxity and loss of subcu­taneous fat occur.

Of the extrinsic factors, ultraviolet and infrared radiation, environmental pollutants and wind play a crucial role. Clinically, photoaging is characterized by coarse wrinkling and furrowing with an apparent thickening of the skin, elastosis and a variety of benign, premalignant and malignant neoplasms.² Histologically, photodamaged skin shows a 20 percent decrease in total collagen and decreased cellular content compared to sun-protected skin.³

Moreover, pigmentary alterations, red superficial blood vessels (telangiectasias) and hyperpigmented areas contribute to an aged appearance by creating shadows and contrast on the face.

Topical preparations to improve the appearance of aged skin fall into four broad categories: Ultra-potent antioxidants, pigment reduction agents, anti-inflammatory global rejuvenators, and genetic and stem cell modulators. We present the latest innovations in each of these categories.

Antioxidants

Antioxidants have long been used in the cosmetic industry for their multifaceted benefits, offering anti-aging and anti-inflammatory properties. In addition, antioxidants confer a degree of photo-protection and anticarcinogenesis by quenching free radical species generated by cellular metabolism and direct exposure to UV radiation. They also block UV-induced inflammatory pathways.

Green tea. The most extensively studied antioxidant, green tea offers antioxidant, anti-inflammatory and anticarcinogenic properties that seem to be beneficial with systemic and topical administration.⁴ Early studies on hairless mice fed green tea showed a dose-dependent reduction of UV-induced carcinogenesis.^{5, 6} Similar anticarcinogenic and chemoprotective effects were shown after green tea polyphenolic catechins (GTP) were topically applied to the mice. GTP is the active ingredient in green tea and limits UV-induced redness, the number of sunburn cells, collagen and cellular DNA damage.⁶

Green tea also has been studied for use in cosmetic applications. In a clinical study of 40 women with moderate photoaging, Chin et al. found increased elastic tissue content in the skin of women who were treated with 300 mg of green tea supplements twice daily and who applied green tea cream daily. Histological improvement, nonetheless, did not correlate with clinical improvement after eight weeks of treatment. This suggests that histological improvement (especially mild to moderate) may not translate into short-term clinical improvement. It also shows that clinically correlating all histological findings is essential.⁷

Vitamin C, vitamin E and ferulic acid. Diet is the sole source of vitamin C in humans. Gastrointestinal absorption is the rate limiting factor in cutaneous delivery of vitamin C. Therefore, even supra-physiological doses of vitamin C through oral administration do not increase the cutaneous concentration to optimal levels.

Exposure to sunlight and environmental pollutants deplete vitamin C from the skin. Even minimal UV exposure of 1.6 times the minimal erythema dose decreases the level of vitamin C to 70 percent of the normal level. Exposure to 10 ppm of ozone in city pollution decreases the level of epidermal vitamin C by 55 percent.⁴

Vitamin E is the most important lipid-soluble, membrane-bound antioxidant in plasma, cellular membranes and tissues. Similar to vitamin C, vitamin E is supplied solely through diet.

In tissues, vitamins C and E act synergistically to provide antioxidant protection. The inherent instability of active vitamin C (L-ascorbic acid), however, remains the major difficulty. When exposed to air, L-ascorbic acid converts to dihydroascorbic acid and turns brown.

To overcome the problem of instability, researchers have stabilized vitamin C and vitamin E preparations with ferulic acid. This is a potent antioxidant present in the cell walls of grains, fruits and vegetables. The acid itself absorbs UV radiation and, therefore, acts as a sunscreen. When mixed with vitamins E and C, it stabilizes the formulation and doubles synergistic photoprotection from four-fold (combined vitamin C and E) to eight-fold (vitamin C, vitamin E, ferulic acid, C E ferulic).⁵ Clinical studies show that topical C E ferulic acid provides substantial protection for human skin against solar simulator-induced oxidative skin damage. This includes erythema, sunburn cell formation and DNA mutations related to skin cancer.⁸

Yquem Extract. This is a novel, highly potent antioxidant. In vitro studies show it leads to highly significant reductions of oxidative stress. Yquem extract at low concentrations (1.5 µg/mL) is highly superior to that of vitamin C (at the concentration of 50 µM) and to that of vitamin E (at 25 µM concentration). In a pivotal clinical study of 10 subjects, the extract was applied for one day to facial skin.

The rates of free radical production were measured 18 hours after the last application and compared to a nontreated zone. In contrast to a control, one product containing yquem extract decreased the rate of free radical production by 22 percent in the treated zone. By comparison, grape polyphenols and idebendone formulations decreased free radical production by only 2.3 percent and 4.1 percent, respectively.⁹

Coffeeberry. Polyphenols are the active ingredients in coffeeberry, the fruit of the coffee plant Coffea arabica. The antioxidant properties of polyphenols are related to their ability to quench free radical production and to prevent cellular damage. In in vitro testing with an oxygen radical absorbance capacity assay, coffeeberry was superior to other commonly used antioxidants, such as green tea extract, pomegranate extract, vitamin C and ­vitamin E.^10,11In clinical trials, 30 patients with significant actinic damage used a skin regimen of 0.1 percent to 1 percent of coffeeberry in skin cleansers and face creams. When compared to pretreatment, all patients saw statistically significant improvements in fine lines, wrinkles, pigmentation and overall skin appearance.¹⁰

Idebenone. This is a synthetic analog of coenzyme Q10. Because of its lower molecular weight, idebenone can penetrate the skin more efficiently than coenzyme Q10. In a clinical study of 50 subjects with moderate photoaging, an application of 0.5 percent or 1 percent idebenone lotion twice daily for six weeks reduced fine lines and wrinkles by 26 percent and 27 percent, respectively. Both groups had a 37 percent improvement in skin hydration and a 30 percent to 33 percent improvement in global photoaging.¹²

Vine shoot. A new generation of ultra-potent antioxidants includes Vitis vinifera shoot, a polyphenol-rich antioxidant, and ectoine/hydroine, a natural blend of compounds found in halophilic microorganisms growing in extreme temperatures and salinity.

In an in vivo clinical study, 56 subjects were treated with a combination of vitis vinifera shoot extract (0.045 percent) and ectoine/hydroine (1 percent). The combination was applied for a four-week period twice daily; 90 percent of patients experienced a 25 percent overall improvement (firmness, radiant glow, evenness, smoothness, hydration, texture, softness) as assessed by an independent investigator.

In in vitro assays, the antioxidant capacity of vitis vinifera shoot appeared to be significantly more powerful than that of vitamin C or vitamin E.⁹

Peptides

These short-chain sequences of amino acids are rapidly expanding the category of cosmeceuticals. Three main categories of cosmeceutical peptides exist.

Signal peptides. These increase fibroblast production of collagen and/or decrease collagenase breakdown of existing collagen. Examples of signal peptides include valine-glycine-alanine-proline-glycine peptide^{13, 14}and lysine-threonine-threonine-lysine-serine peptide.¹⁵

Neuropeptides. Also known as neuro­transmitter-affecting peptides, these mimic the effects of botulinum toxin. Clinically, neuropeptides decrease facial muscle contraction, therefore reducing lines and wrinkles by raising the threshold for minimal muscle activity. Over time, they also reduce subconscious muscle movement.

In one open label trial, 10 female patients applied a 5 percent acetyl-hexapeptide-3 cream twice daily. Subjects experienced a 27 percent improvement in periorbital rhytids after 30 days as measured by silica replica analysis.¹⁶

Carrier peptides. These stabilize and deliver important trace elements necessary for wound healing and enzymatic processes into the skin. The most commonly encountered carrier peptides stabilize and deliver copper, an elemental metal for proper wound healing, enzymatic processes and aniogenesis, which is the production of new blood vessels.¹⁷

Pigment Modifying Agents

Even skin pigmentation is considered a universal sign of youth and beauty. Pigmentary alterations and uneven pigmentation occur from skin injury, advancing age or a combination of the two.

Hydroquinone. Also known as benzene- 1,4-diol, hydroquinone is the most effective pigment-lightening agent available. It functions by inhibiting the enzymatic action of tyrosinase, a key enzyme in the melanin pigment synthesis. Hydroquinone also inhibits RNA and DNA synthesis and alters melanosome (pigment pocket within melanocyte) formation. In addition, it suppresses the melanocyte metabolic processes, inducing the gradual reduction of melanin production.

In cosmetic medicine, hydroquinone is used as a topical application. The maximum concentration, available by prescription only, is 4 percent, and a plethora of 2 percent preparations are available over the counter.¹⁸

In recent years, hydroquinone has come under fire. Specifically, it may cause ochronosis, which is a bluish black discoloration of treated sites.¹⁹ What causes this remains unknown. It could be hydroquinone itself, high concentrations of it or other substances that exist in the preparations.

Furthermore, when systemically administered to rodents in very high quantities, hydroquinone was reported to be carcinogenic. Even though the human potential for carcinogenicity has not been demonstrated, hydroquinone is banned in some countries, such as France.

In the United States, the issue of safety and efficacy of hydroquinone was the subject of a much publicized Food and Drug Administration investigation. After an initial investigation, however, the FDA took no formal action banning over-the-counter hydroquinone.

Niacinamide. Also known as nicotinamide, niacinamide is a water-soluble component of the vitamin B complex group. In vivo, nicotinamide is incorporated into nicotinamide adenine dinucleotide and nicotinamide adenine dinucleotide phosphate. These coenzymes participate in a variety of enzymatic oxidation reduction reactions, including tissue mitochondrial respiration and lipid metabolism.

Niacinamide inhibits melanine transfer to keratinocytes. Bissett et al. showed that niacinamide reduced hyperpigmented macules, fine lines and wrinkles, red blotchiness, and skin sallowness. It also increased skin elasticity.^20-23 In addition, it helped alleviate some of the symptoms of rosacea by increasing hydration, reducing transepidermal water loss and improving barrier function of the stratum corneum.

Edelweiss Complex. A new strategy to target skin discoloration relies on antisense oligoneucleotides, which block targeted gene transcription on the molecular level. Researchers at Dior’s Innovation Centre in St. John Dubrey, France, have developed a unique antisense strategy to modulate melanogenesis. Antisense technology specifically blocks activated tyrosinase and halts pigment production at the cellular, DNA level.

This technology offers unprecedented specificity, biological stability and safety in whitening all skin types. In a clinical study of 30 Asian patients with dyschromia of the hands, the test product application twice daily for eight weeks significantly whitened hyperpigmented and normal skin.²⁴

Global Rejuvenators

The visible signs of skin aging are linked to a precise zone in the orchestral areas of the skin, termed Aging Responsible Interface (ARI). This zone is composed of three main elements: the deepest layers of the epidermis (top layer of the skin); the superficial dermis (bottom layer of the skin); and the interface between the dermis and epidermis.

Molecular studies of ARI identified 20 independent markers of youth. Markers located in the dermis are strongly associated with facial sagging and wrinkles. Those located in the epidermis and at the interface alter epidermal formation and turnover. They also affect skin resistance and influence skin complexion and radiance.

Using the DNA chips analysis of ARI zone, Dior’s research laboratories identified, at the molecular level, the skin constituents altered by chronological aging. They also identified the active ingredients to correct these alterations. DNA chip analysis led to the discovery of a global and complete ARI modifying system, which targets all 20 markers of aging.²⁵ As this article demonstrates, we have entered a new and exciting era in cosmetic dermatology. New generation cosmeceuticals offer unprecedented capabilities of gene targeting and specific, tissue-directed therapies. The explosion of primary scientific data on the natural history of the skin aging process continues to yield new and attractive potential therapeutic targets. The future, indeed, looks bright.

FOUR MAJOR FACTORS DEFINING THE FUTURE OF SKIN CARE

“The following 4R’s defining the future of skincare, encompassing most of the marketing claims consumers encounter, as well as outlining the importance of actives and their delivery systems, simultaneously.”

The 4R’s of delivery:

• Right chemical
• Right site
• Right concentration
• Right period of time

“Usually the active gets the credit for the efficacy, but it must be delivered in a safe, stable and effective fashion.  That is the role of the base and the delivery system.  In the end, what matters is the value added in the product to attract consumers to purchase the product.  Marketing delivery systems together with active ingredients is important to the consumers.”

“Delivery systems exist to improve the efficacy of an active in a formulation.”

Natural or Organic – an ongoing debate Where is the standardization and safety in the cosmetics arena?

The Cosmetic industry is aware that consumers are trending toward inner and outer well-being, which is impacting their spending behavior and decisions, from the foods they eat to the cosmetics they use. There is a lot of confusion in the personal care industry over which ingredients are healthy for the skin.

The term “natural” is not regulated by the FDA, which basically leaves each vendor to set its own standards for what the term means. Some brands marketed as “natural” are formulated with high concentrations of plant-based and naturally derived ingredients, and fewer parabens, sodium lauryl sulfate, phthalates, petrochemicals, and synthetic fragrances or dyes. We are seeing more natural preservatives, emulsifiers, etc. Current labeling standards are open to interpretation and allow products to be called “natural” even if only a small percentage of ingredients could technically fall under that umbrella.

The definition of “organic” refers to products containing ingredients grown and processed without the use of pesticides, herbicides, or insecticides. ‘Organic’ describes how it was grown. These regulations fall under the US Department of Agriculture (USDA)’s standards for organic foods. Since 2006, the USDA began allowing beauty companies to use its USDA organic seal on products that meet its requirements for food.

The requirements for labeling a product as “natural” are far less defined than the requirements for labeling a product as “organic.” Marketers seeking to create impact with performance are using natural ingredients as a key element of their marketing strategy in cosmetics and toiletries with a noticeable shortage of clinical data that actually proves that these products are effective. Some brands are picking up on this selling point by incorporating a “chemical-free” or “preservative-free” message into their product labeling. Differentiating between the levels of quality within the natural sector is proving to be a great challenge for skin care experts, physicians, and retailers alike.

The need to create a common definition and logo for natural and organic products is a recurring theme during conferences in Europe and USA. Many participants were surprised to discover that organic-certified products in France have to contain just 10 percent of organic ingredients to earn the “bio” label domestically. Meanwhile, natural cosmetics, called “eco” in France, only need to contain 5 percent of organic ingredients. The requirements also vary widely from country to country for natural and organic cosmetics.

Beauty retailer Sephora, CA, now categorizes products it sells as “natural” or “organic.” Estee Lauder-owned Origins has added a “certified organic” range to keep up with pressure from new competitors.  Some brands are picking up on this selling point by incorporating a “chemical-free” or “preservative-free” message into their product labeling.

TARGET STORES TO LAUNCH NINE NATURAL / ORGANIC BRANDS

Retailer “Target” unveiled this month a new line of certified natural and Organic skin care products developed exclusively for multicultural skin types. On the mass-market level, Aveeno is one of the most successful brands in the natural segment, with its skin care range based on Johnson & Johnson’s patented active natural ingredient Feverfew, as well as soy, oats, and shiitake mushroom. Provencale beauty rang+e–Occitane, is certified organic by ECOCERT.

European Union (EU) has more strin gent and protective laws for cosmetics than USA does. If Ecocert is approved by the USDA, then certification by Ecocert is just as good as certification provided by the USDA.

In USA the regulation of cosmetics is woefully outdated. FDA needs to know who is making personal care products, and what products they are making, as a basic first step to protecting the public health. Ingredients and products are not subject to FDA premarket approval authority, with the exception of color additives. FDA has virtually no power to perform even the most rudimentary functions needed to ensure the safety of an estimated $35 billion of personal care products purchased by consumers annually The safety of personal care product ingredients is evaluated through a voluntary industry program known as the Cosmetic Industry Review (CIR) process. In the absence of the CIR program, there would be no systematic examination of the safety of individual cosmetic ingredients.

The recent draft legislation of FDA globalization Act of 2008 is a major step by FDA to update the Federal Food, drug and Cosmetic Act. It requires any facility engaged in manufacturing, processing packaging or holding of cosmetics in the US or for import to the US shall be required to register (and pay registration fees) under subsections (a) and (b) of section 604 of the Federal Food, drug and Cosmetic Act. The act also requires adverse-event reporting for cosmetics.

Who Developed the First Skin Care Product?