Applications of Popular Botanical Ingredients in OTC Skincare Popular in cosmeceutical regimens, botanicals are increasingly available in OTC products to moisturize, soothe itch, and provide other benefits.

By Jeanine B. Downie, MD

otanical extracts have been used on the skin for dermatitis, a common allergic reaction to .3 A millennia. Contemporary written reports and novel parthenolide-free extract of feverfew (PFE-fever- accumulated evidence tell us that Cleopatra few) compound has removed the parthenolide compo- Bused botanical-based topical formulations for nent to obviate the sensitization potential. In one cosmetic purposes and to condition her skin. Today, study, the agent had in vitro anti-inflammatory the US cosmeceutical market is an estimated $10-14 effects, as indicated by a reduction in release of pro- billion industry, and a majority of those products are inflammatory cytokines. In vivo, PFE-feverfew built upon botanical extracts. Botanical ingredients reduced DNA damage and hyperplasia following UV are also now incorporated into many mass-market exposure. There was also a reduction in UV-induced skincare products developed for both adults and chil- skin erythema as a result of PFE-feverfew dren. Following is a look at some of the more popular application.4 botanical ingredients used in mass-market skincare Another trial confirmed the ability of PFE-feverfew products. The emphasis is on topical application and to inhibit the activity of pro-inflammatory enzymes skincare formulations, not on oral botanical-based supplements. Take-Home Tips. Botanical ingredients are now incorporated into many mass-market skincare products developed for both adults and Feverfew children. If patients are interested in “natural” or botanical A popular topical botanical currently is feverfew skincare, the accumulated evidence suggests that some products may ( ), a member of the sunflower family. Feverfew’s common name derives from its be worthwhile. For patients with “sensitive skin,” eczema, atopic ancient oral use as a fever reducer. The antioxidant- dermatitis, or any acute or chronic, inflammatory, pruritic skin rich botanical is shown to have anti-inflammatory, condition, products containing feverfew, colloidal oatmeal, or anti-irritant, and anti-cancer properties and is used as sunflower seed oil may be useful adjuncts to other therapeutic an oral supplement to treat migraine headaches.2 interventions. Patients with rosacea and pigmentary alterations may One challenge associated with the topical applica- benefit from products featuring licorice root extract. ● tion of feverfew derivatives is the risk of parthenium

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Limitations of the Research Colloidal oatmeal Colloidal oatmeal is derived from dehulled oat ker- When it comes to topically-applied botanical ingredients, it is nels. The active components include polysaccharides, important that an individual evaluating products keep in mind the proteins, lipids, enzymes, saponins, flavonoids, vita- limitations of the available data. As dermatologists know, pub- mins, and prostaglandin synthesis inhibitors. Use of lished studies often document the biological activities of botani- finely ground colloidal oatmeal (Avena sativa L.) to cal ingredients ingested orally or applied topically, but there are soothe skin is an ancient practice, and the use of oat- generally few published controlled trials of finished formula- meal baths is still common to help control pruritic, tions. So, for example, while there is good scientific evidence inflammatory skin manifestations like poison ivy and that topically applied confers local anti-inflammatory chicken pox. Colloidal oatmeal functions as a effects, it is less clear what concentration of aloe vera is neces- cleanser, moisturizer, buffer, as well as a soothing and 6 sary to confer those benefits or whether any particular aloe-con- protective anti-inflammatory agent. Colloidal oatmeal taining lotion is more beneficial than another. has been used to treat atopic dermatitis and inflam- matory skin diseases and is known to repair barrier Furthermore, when it comes to botanical ingredients, the qual- dysfunction, reduce skin inflammation and irritation.2 ity of the raw botanical material is a crucial consideration. Many The anti-pruritic effects of colloidal oatmeal were respected manufacturers derive botanical ingredients only from demonstrated in a study of burn wounds. Patients specific, controlled crops to ensure quality and consistency. who applied to healing burn wounds a topical mois- These important considerations are not necessarily limitations turizer containing colloidal oatmeal reported signifi- of topical botanicals, as many high-quality botanical-based cantly less itch and used fewer antihistamines than skincare formulations are currently on the market. These have patients who used the vehicle moisturizer without demonstrated clinical effectiveness, achieved high levels of colloidal oatmeal.7 patient and physician endorsement, and in many cases have con- Colloidal oatmeal also provides protective and trolled data to support their efficacy. Physicians interested in moisturizing benefits, thought to derive from the high learning more about specific formulations can contact the manu- concentration of starches and beta-glucans that hold facturers with requests for information. Trusted manufacturers water.7 The botanical is high in oat phenols, some of test their finished formulations in controlled trials that may not which are strong ultraviolet absorbers and under always be as rigorous as pharmaceutical drug trials but are gen- investigation as sunscreen ingredients.7 erally well-designed and reliable. Colloidal oatmeal is featured in Aveeno Baby Soothing Relief products, including creamy wash, bath treatment, and moisture cream, as well as and the release of pro-inflammatory mediators from Aveeno Baby Daily Care washes and moisturizer, and macrophages and from human peripheral blood Aveeno Skin Relief BodyWash. Aveeno Daily moistur- mononuclear cells. In vivo, PFE-feverfew inhibited izing lotion and Aveeno Eczema Care also feature col- dermatitis in two different murine models.5 loidal oatmeal. Eucerin Calming Crème Daily mois- Most feverfew-containing skincare products are turizer is a fragrance-free formulation that also fea- intended for anti-aging use or to manage adult der- tures oatmeal to moisturize the skin and soothe itch. matoses, such as rosacea. However, given its efficacy Eucerin Calming itch treatment adds menthol for in combating dermatoses in vivo, there is increasing additional anti-pruritic effect. interest in using feverfew for atopic dermatitis and “sensitive skin.” PFE-feverfew is formulated into the Sunflower seed oil Aveeno Active Naturals line in their “Ultra-Calming” Botanically-derived oils have been studied as possible products. These include a facial cleanser, daily facial low-cost moisturizers, but studies suggest variability moisturizer with SPF, and a sunscreen, which may be in their effectiveness. For example, application of sun- suitable for use on eczema-prone skin and rosacea. flower (Helianthus annuus) seed oil was shown to

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accelerate epidermal barrier function repair in mouse Licochalcone is incorporated into the Eucerin models, while other botanical oils actually delayed Redness Relief System, which includes cleanser, SPF repair.8 When sunflower seed oil was applied three- moisturizer, and a nightly serum. TNS Essential times daily to preterm infants in one study, it was Serum has licorice in it as well as Vivite Vibrance. shown to improve overall skin health and reduce Both cosmeceuticals help to even out skin tone and nosocomial infections compared to controls.9 improve texture. Sunflower seed oil contains high levels of essential fatty acids, including linoleic acid. A novel sunflower Lavender and oleodistillate (SOD) has been shown to increase epi- Lavender (Lavandula angustifolia or Lavandula offici- dermal lipid synthesis and to reduce inflammation in nalis) takes its name from the Latin word “to wash,” vitro and in animal models. In one study, an SOD 2% presumably because it was commonly used as a fra- emulsion demonstrated moisturizing properties in 20 grance in baths. Lavender oil is shown to have strong adult volunteers with atopic skin and had a strong antioxidant properties.15 Orally, lavender oil supple- steroid-sparing effect. Other studies in infants and mentation has been associated with anti-inflammatory babies with AD have shown a positive impact on and analgesic effects.16 Topically applied lavender oil quality-of-life parameters.10 has shown antimicrobial effects17,18 and is under inves- Sunflower oleodistillate is the primary compo- tigation as an anti-tick treatment.19 nent of Stelatopia products from Mustela, which Despite these potential uses for topical lavender include moisturizing cream, cream cleanser, and oil, currently its primary use in skincare products is milky bath oil. as an anxiolytic and sleep-promoting fragrance. Studies have shown that lavender oil aromatherapy Licorice root extract effectively reduces anxiety in mouse models of One of the more popular botanical skincare ingredi- induced anxiety with demonstrated effects on neuro- ents lately is “licorice root” (Glycyrrhiza glabra) or transmitters such as dopamine, serotonin, and their “licorice root extract.” The main components of derivatives.20 In various trials, lavender aromatherapy licorice extract are triterpene saponins—glycyrrizin, has been shown to reduce anxiety among dental flavonoids—liquiritigenin, and isofavonoids— patients,21 pre-surgical patients,22 and test-taking grad- glabidrin. In reality, at least seven constituents have uate nursing students.23 been derived from the licorice root, and six of these Studies show that unstable lavender oil exposed to have been shown to have significant antioxidant oxidation has the potential to induce allergic reac- capacity. Glabridin was found to be the most abun- tions,24 although no widespread reports of lavender dant and potent antioxidant, while Formononetin was allergy are in the literature. In fact, in mouse models, not found to have notable antioxidant effects.11 topical application of lavender oil was shown to inhib- Glabridin has anti-tyrosinase activity,12 leading to its it immediate type allergic reactions.25 widespread use in cosmeceutical products intended to Chamomile (Matricaria recutita) contains the flavi- manage dyschromia and other pigmentary alterations. noid apigenin, which is suggested to have antitumor A novel constituent of licorice extract, licochalcone effects.26 Chamomile also has anti-inflammatory, A appears to induce an anti-inflammatory effect antimicrobial, and wound-healing benefits.27 Aveeno through the inhibition of COX-2-dependent PGE2 pro- Baby Calming Comfort bath and lotion contain laven- duction.13 In one trial, when patients with mild to der extracts for fragrance. Avalon Organics incorpo- moderate facial erythema used licochalcone-containing rates Lavender into several facial cleansing products. skincare for eight weeks, they had significant improve- Nature’s Baby Organics makes a wash with lavender ments in erythema scores at weeks four and eight and and chamomile. Aquaphor Baby Gentle Wash and reported improved quality of life.14 The skincare prod- Shampoo contains chamomile, as does Mustella baby ucts were found to be compatible with metronidazole. shampoo.

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2. Schiapparelli P, Allais G, Castagnoli Gabellari I, Rolando S, Terzi MG, Benedetto C. Non-pharmaco- : A Potential Allergen logical approach to migraine prophylaxis: part II. Neurol Sci. 2010 Jun;31 Suppl 1:S137-9. 3. Sharma VK, Sethuraman G. Parthenium dermatitis. Dermatitis. 2007 Dec;18(4):183-90. 4. Martin K, Sur R, Liebel F, Tierney N, Lyte P, Garay M, Oddos T, Anthonavage M, Shapiro S, Southall Tea tree oil is increasingly popular as a topical antiseptic and M. Parthenolide-depleted Feverfew (Tanacetum parthenium) protects skin from UV irradiation and external aggression. Arch Dermatol Res. 2008 Feb;300(2):69-80. antimicrobial. A number of washes, shampoos, and therapeutic 5. Sur R, Martin K, Liebel F, Lyte P, Shapiro S, Southall M. Anti-inflammatory activity of parthenolide- formulations are available and marketed to reduce risks of cuta- depleted Feverfew (Tanacetum parthenium). Inflammopharmacology. 2009 Feb;17(1):42-9. 6. Kurtz ES, Wallo W. Colloidal oatmeal: history, chemistry and clinical properties. J Drugs Dermatol. neous bacterial and fungal infections or treat acne, despite limit- 2007 Feb;6(2):167-70. 7. Matheson JD, Clayton J, Muller MJ. The reduction of itch during burn wound healing. J Burn Care ed positive data. Due to its popularity, the agent may attract the Rehabil. 2001 Jan-Feb;22(1):76-81 interest of patients. Tea tree oil has been associated with high 8. Darmstadt GL, Mao-Qiang M, Chi E, Saha SK, Ziboh VA, Black RE, Santosham M, Elias PM. Impact of topical oils on the skin barrier: possible implications for neonatal health in developing countries. Acta and increasing rates of allergic contact reactions.28,29,30 Given this Paediatr. 2002;91(5):546-54. 9. Darmstadt GL, Badrawi N, Law PA, Ahmed S, Bashir M, Iskander I, Al Said D, El Kholy A, Husein MH, rate of allergic reactions and the limited evidence to support its Alam A, Winch PJ, Gipson R, Santosham M. Topically applied sunflower seed oil prevents invasive bac- utility, tea tree oil should not be widely recommended for der- terial infections in preterm infants in Egypt: a randomized, controlled clinical trial. Pediatr Infect Dis J. 2004 Aug;23(8):719-25. matologic indications at this time. 10. Eichenfield LF, McCollum A, Msika P. The benefits of sunflower oleodistillate (SOD) in pediatric dermatology. Pediatr Dermatol. 2009 Nov-Dec;26(6):669-75. 11. Vaya J, Belinky PA, Aviram M. Antioxidant constituents from licorice roots: isolation, structure elu- Potential Adjuncts cidation and antioxidative capacity toward LDL oxidation. Free Radic Biol Med. 1997;23(2):302-13. 12. Yokota T, Nishio H, Kubota Y, Mizoguchi M. The inhibitory effect of glabridin from licorice extracts Patients often ask their dermatologist or office staff on melanogenesis and inflammation. Pigment Cell Res. 1998 Dec;11(6):355-61. about skincare products, running the gamut from 13. Furuhashi I, Iwata S, Shibata S, Sato T, Inoue H. Inhibition by licochalcone A, a novel flavonoid iso- lated from root, of IL-1beta-induced PGE2 production in human skin fibroblasts. J Pharm products featured in infomercials to high-end cosme- Pharmacol. 2005 Dec;57(12):1661-6. ceuticals, and, of course, mass-market skincare. 14. Weber TM, Ceilley RI, Buerger A, Kolbe L, Trookman NS, Rizer RL, Schoelermann A. Skin tolerance, efficacy, and quality of life of patients with red facial skin using a skin care regimen containing Clinicians may lack detailed information about partic- Licochalcone A. J Cosmet Dermatol. 2006 Sep;5(3):227-32. ular products and ingredients. In general, use of a gen- 15. Yang SA, Jeon SK, Lee EJ, Shim CH, Lee IS. Comparative study of the chemical composition and antioxidant activity of six essential oils and their components. Nat Prod Res. 2010;24(2):140-51. tle, soap-free, moisturizing cleanser is always appropri- 16. Hajhashemi V, Ghannadi A, Sharif B. Anti-inflammatory and analgesic properties of the leaf ate. If parents are interested in “natural” or botanical extracts and essential oil of Lavandula angustifolia Mill. J Ethnopharmacol. 2003 Nov;89(1):67-71. 17. Kunicka-Styczyƒska A, Sikora M, Kalemba D. Lavender, tea tree and lemon oils as antimicrobials in skincare, the accumulated evidence suggests that some washing liquids and soft body balms. Int J Cosmet Sci. 2010 Jun 21. Epub products may be worthwhile. For patients with “sensi- 18. Lodhia MH, Bhatt KR, Thaker VS. Antibacterial activity of essential oils from palmarosa, evening primrose, lavender and tuberose. Indian J Pharm Sci. 2009 Mar;71(2):134-6. tive skin,” eczema, atopic dermatitis, or any acute or 19. Pirali-Kheirabadi K, Teixeira da Silva JA. Lavandula angustifolia essential oil as a novel and promis- chronic, inflammatory, pruritic skin condition, prod- ing natural candidate for tick (Rhipicephalus (Boophilus) annulatus) control. Exp Parasitol. 2010 Apr 28. Epub ucts containing feverfew, colloidal oatmeal, or sun- 20. Tsang HW, Ho TY. A systematic review on the anxiolytic effects of aromatherapy on rodents under flower seed oil may be useful adjuncts to other thera- experimentally induced anxiety models. Rev Neurosci. 2010;21(2):141-52. 21. Kritsidima M, Newton T, Asimakopoulou K. The effects of lavender scent on dental patient anxiety peutic interventions. Patients with rosacea and pig- levels: a cluster randomised-controlled trial. Community Dent Oral Epidemiol. 2010 Feb;38(1):83-7. mentary alterations may benefit from products featur- 22. Braden R, Reichow S, Halm MA. The use of the essential oil lavandin to reduce preoperative anxi- ety in surgical patients. J Perianesth Nurs. 2009 Dec;24(6):348-55. ing licorice root extracts. The listing of brands and 23. McCaffrey R, Thomas DJ, Kinzelman AO. The effects of lavender and essential oils on product lines provided here is not exhaustive, and test-taking anxiety among graduate nursing students. Holist Nurs Pract. 2009 Mar-Apr;23(2):88-93. 24. Hagvall L, Sköld M, Bråred-Christensson J, Börje A, Karlberg AT. Lavender oil lacks natural protec- inclusion of a product is not an endorsement. What- tion against autoxidation, forming strong contact allergens on air exposure. Contact Dermatitis. 2008 ever product they consider, patients should carefully Sep;59(3):143-50. 25. Kim HM, Cho SH. Lavender oil inhibits immediate-type allergic reaction in mice and rats. J Pharm evaluate the offerings with the guidance of their physi- Pharmacol. 1999 Feb;51(2):221-6. cian. Generally, consumers do best to choose estab- 26. Li B, Birt DF. In vivo and in vitro percutaneous absorption of cancer preventive flavonoid apigenin in different vehicles in mouse skin. Pharm Res. 1996 Nov;13(11):1710-5. lished brands and/or those that provide detailed data 27. Jarrahi M. An experimental study of the effects of Matricaria chamomilla extract on cutaneous burn about the performance of their specific formulations. wound healing in albino rats. Nat Prod Res. 2008 Mar 20;22(5):422-7. 28. Simpson EL, Law SV, Storrs FJ. Prevalence of botanical extract allergy in patients with contact der- Lavender and chamomile-containing formulations matitis. Dermatitis. 2004 Jun;15(2):67-72. may have less utility in terms of promoting skin 29. Rutherford T, Nixon R, Tam M, Tate B. Allergy to tea tree oil: retrospective review of 41 cases with health, but these products appear to do no harm to positive patch tests over 4.5 years. Australas J Dermatol. 2007 May;48(2):83-7. 30. Zug KA, Warshaw EM, Fowler JF Jr, Maibach HI, Belsito DL, Pratt MD, Sasseville D, Storrs FJ, Taylor most skin and may have calming and soothing bene- JS, Mathias CG, Deleo VA, Rietschel RL, Marks J. Patch-test results of the North American Contact ■ ❑✔ Dermatitis Group 2005-2006. Dermatitis. 2009 May-Jun;20(3):149-60. Erratum in: Dermatitis. 2009 fits for adults and children, especially babies. Oct;20(5):300. 1. Wu J. Anti-inflammatory ingredients. J Drugs Dermatol. 2008 Jul;7(7 Suppl):s13-6. 31. Fowler JF Jr, Woolery-Lloyd H, Waldorf H, Saini R. Innovations in natural ingredients and their use in skin care. J Drugs Dermatol. 2010 Jun;9(6 Suppl):S72-81.

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