8/6/2019 Rosmarinic Acid cal Critique

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30 AESTHETIC DERMATOLOGY J U N E 2 0 0 9 S K I N & A L L ER G Y N EW S

Rosmarinic acid (alpha-o-caffeoyl-3,4-dihydroxyphenyl lactic acid)is a naturally occurring hydrox-

ylated compound and analogue of caf-feic acid (3,4-dihydroxycinnamic acid).

Caffeic acid, which is one of the mainhydroxycinnamic acids (a ma- jor class of phenolic com-pounds), confers antioxidantactivity, protects human skinfrom ultraviolet Cinducederythema, and exhibits con-siderable anticarcinogenic po-tential (J. Nutr. 2001;131:66-71; Folia Biol. [Praha] 2003;49:197-202; Int. J. Pharm.2000;199:39-47; Nutr. Cancer1998;32:81-5).

Caffeic acid and its deriv-atives, such as rosmarinicacid, carnosol, and carnosic acidall of

which manifest antioxidant activityare thought to be the key constituentsof rosemary. Caffeic acid also is foundin coffee, several grains, fruits, and veg-etables, including white grapes, olives,spinach, cabbage, and asparagus, as wellas white wine and olive oil (Phytother.Res. 2003;17:987-1000; Indian J. Exp.Biol. 1999;37:124-30).

Notably, rosmarinic acid is a commoncomponent of some fern and hornwortspecies, as well as species of the Boragi-naceae family and, particularly, the Lami-aceae family (Phytochemistry 2003;62:121-5). The Lamiaceae family includescommon culinary herbs such as basil,lavender, lemon balm, marjoram,

oregano, peppermint, perilla, sage, sa-vory, thyme, and rosemary.

A dimer of caffeic acid, rosmarinicacid is well absorbed through the gas-trointestinal tract and the skin, and hasbeen shown to augment prostaglandinE2 production and reduce leukotriene B4production in human polymorphonu-clear leukocytes (Indian J. Exp. Biol.1999;37:124-30).

Rosmarinic acid is versatile, and it isused in food preservatives, cosmetics,and medical applications by dint of its an-timicrobial, antiviral, antioxidant, anti-in-flammatory, and immunomodulatoryproperties (Indian J. Exp. Biol. 1999;

37:124-30; Phytochemistry 2003;62:121-5; J. Agric. Food Chem. 2001;49:5165-70;J. Dermatol. 2008;35:768-71; Photochem.Photobiol. 2006;82:1668-76).

This column will briefly discuss the re-search and potential dermatologic ap-plications of this phenolic compound.

Anti-Inflammatory ActionsTwenty years ago, rosmarinic acid wasidentified as a nonsteroidal anti-inflam-matory agent.

In a 1989 study, researchers intra-venously and topically administered theantioxidant polyphenol to rats to assesshow different routes of administrationaffect absolute bioavailability and relat-ed tissue distribution.

They found absolute bioavailability tobe high for both IV and topical admin-

istration (60% for topical administra-tion), with a longer lag time associatedwith percutaneous administration, sug-gesting that rosmarinic acid is well ab-sorbed from the gastrointestinal tract as

well as the skin.The investigators conclud-

ed that rosmarinic acid haspotential as a therapeutic non-steroidal anti-inflammatoryagent (Methods Find. Exp.Clin. Pharmacol. 1989;11:345-52).

During the ensuing 2decades, a variety of benefi-cial activities were associatedwith rosmarinic acid, sug-gesting medical indications.In 2004, Osakabe et al. de-termined that oral supple-

mentation with the polyphenol was an

effective treatment for seasonal allergicrhinoconjunctivitis, due to inhibition ofthe inflammatory response and the scav-enging of reactive oxygen species ex-hibited by the compound (Biofactors2004;21:127-31).

Antitumorigenic ActionsThe same year, Osakabe et al. reportedon the antitumorigenic ef-fects of a rosmarinicacidrich Perilla frutescensextract in a two-stagemurine skin cancer model.They noted significant sup-pression of tumorigenesisas a result of the topical ap-

plication of 2 mg/mouse of the extractfollowing tumor initiation with 7,12-di-methylbenz[a]anthracene (DMBA).

Tumor promotion was achieved bythe use of 12-tetradecanoylphorbol 13-acetate (TPA). The researchers notedthat anti-inflammatory activity 5 hoursafter TPA treatment was equivalent be-tween a perilla extract containing 68%rosmarinic acid and a commercially avail-able rosmarinic acid.

In addition, TPA-induced increases inmyeloperoxidase activity, as well as theproduction of certain chemokines, weresignificantly reduced by pretreatmentwith perilla extract or rosmarinic acid,

as were expression levels of intercellu-lar adhesion molecule-1 and vascularcell adhesion molecule-1 mRNA. Fur-thermore, pretreatment with the ex-tract or with commercial rosmarinicacid significantly reduced reactive oxy-gen radical synthesis (of 8-hydroxy-2-de-oxyguanosine) induced by double treat-ment of TPA.

The investigators attributed part ofthe anticarcinogenic activity of P.frutescens to the independent mecha-nisms associated with rosmarinic acid,free radical scavenging, and inflamma-tory response suppression (Carcinogen-esis 2004;25:549-57).

Antimicrobial ActionsIn 2006, Moreno et al. investigatedRosmarinus officinalis extracts to identify

their bioactive constituents and proper-ties, as well as the distribution and levelsof antioxidants. They found a strongcorrelation between antioxidant activityand total phenol content, with all rose-

mary extracts displaying significant rad-ical scavenging activity.

A methanol extract that contained30% carnosic acid, 16% carnosol, and5% rosmarinic acid was substantiallymore effective as an antimicrobial agentagainst gram-positive bacteria, gram-negative bacteria, and yeast than was awater extract containing 15% ros-marinic acid.

The investigators concluded that theantimicrobial activity of rosemary ex-tracts was linked to their phenolic com-position, and that carnosic acid and ros-marinic acid are probably the primaryantimicrobial components of rosemary

(Free Radic. Res. 2006;40:223-31).

PhotoprotectionLater that year, Psotova et al. examinedthe protective effects ofPrunella vulgarisand rosmarinic acid, its primary pheno-lic constituent, against alterations in-duced by UVA exposure in a human ker-atinocyte cell line. For 4 hours, human

keratinocytes exposed to UVA (10-30J/cm2) were treated with 1-75 mg/L ofP. vulgaris extract or 0.9-18 mg/L of ros-marinic acid.

Both P. vulgaris extract and ros-marinic acid mitigated UVA-inducedloss of cell viability and significantly in-hibited the production of free radicalsengendered by UVA exposure. DNAdamage also was lessened as a result ofpostexposure treatment with both com-pounds.

The investigators, who noted that P.vulgaris and rosmarinic acid are used incosmetics, concluded that both botani-cals exhibit concentration-dependent

photoprotection and have potential assupplementary photoprotective agentsin dermatologic formulations (J. Pho-tochem. Photobiol. B 2006;84:167-74).

Also in 2006, investigators topicallyapplied caffeic acid and its analogues,such as rosmarinic acid, to the abdomensof live hairless mice, and found that thepolyphenols inhibited the production ofreactive oxygen species upon exposure toUVA. They achieved similar resultsthrough oral administration of thepolyphenols (Photochem. Photobiol.2006;82:1668-76).

In 2007, Lee et al. conducted severalexperiments with B16 melanoma cells toidentify the effects of rosmarinic acid onmelanogenesis. They found that thepolyphenol elevated melanin contentand tyrosinase expression in a concen-

tration-dependent fashion, and that pro-tein kinase A was involved in and medi-ated the melanogenesis spurred by ros-marinic acid (Biochem. Pharmacol.2007;74:960-8).

Early in 2009, Snchez-Campillo et al.performed in vitro and in vivo experi-ments that showed rosmarinic acid actsas an exogenous photoprotective agent by scavenging free radicals. The re-searchers also found that rosmarinic acidacts as an endogenous photoprotector byactivating the bodys defense mecha-nisms through the regulation of tyrosi-nase activity and the initiation ofmelanin synthesis.

In particular, in vivo experimentsshowed that UVA-exposed mice orallytreated with rosmarinic acid displayedonly slight dysplasia (in 30% of cases),whereas UVA-exposed mice fed a control

diet exhibited severe or moderate dys-plasia in all cases (Food Chem. Toxicol.2009;47:386-92).

Atopic DermatitisIn 2008, Lee et al. assessed the effects ofrosmarinic acid on mild atopic der-matitis in 21 patients (14 females, 7males) aged 5-28 years. Twice daily, a

0.3% rosmarinic acid emulsionwas topically applied to elbowflexures for 8 weeks. Erythemaon the antecubital fossa wassignificantly diminished at 4and 8 weeks, and transepider-mal water loss from the ante-cubital fossa was significantly

lower at 8 weeks than at baseline, ac-cording to local Severity Scoring ofAtopic Dermatitis index results.

Xerosis, pruritus, and general symp-toms all improved, according to the re-sults of self-administered questionnaires.The investigators concluded that ros-marinic acid warrants consideration as atherapeutic agent for atopic dermatitis (J.Dermatol. 2008;35:768-71).

Rosmarinic acid can be obtainedthrough the diet or as an oral supple-ment pill, and it is used in cosmetic for-mulations with numerous other ingre-dients.

ConclusionRosmarinic acid is a significant polyphe-nol with an apparently wide range ofpotential and realized dermatologic ap-plications.

The direction of current research ispromising, but much more work is stillrequired to determine how importantthis antioxidant will be in the derma-tologic armamentarium. To date,atopic dermatitis may be the indicationfor which this herbal ingredient is bestsuited.

DR. BAUMANN is director of cosmeticdermatology at the University of Miami.To respond to this column, or to suggesttopics for future columns, write to Dr.Baumann at our editorial offices via e-mailat sknews@elsevier.com.

COSMECEUTICAL CRITIQUE

Rosmarinic Acid

BY LESL IE S .

B A U MA N N, M . D.

Rosmarinic acid acts as an exogenous

photoprotective agent by scavenging free

radicals and as an endogenous photoprotector

by activating the bodys defense mechanisms.