Whitening Agent Presentation

WHITENING AGENTWHITENING AGENT

By Mohammad ZakyBy Mohammad Zaky

PEMBAGIAN KOSMETIKAPEMBAGIAN KOSMETIKA

Berdasarkan Surat Keputusan Menteri Berdasarkan Surat Keputusan Menteri Kesehatan Nomor 045/C/ SK/1977 Kesehatan Nomor 045/C/ SK/1977 tanggal 22 januari 1977, menurut tanggal 22 januari 1977, menurut kegunaannya kosmetik dikelompokkan kegunaannya kosmetik dikelompokkan dalam beberapa golongan yaitu : dalam beberapa golongan yaitu :


1.1. Sediaan untuk bayi; shampoo bayi, losion, baby oil, bedak, krim, dan Sediaan untuk bayi; shampoo bayi, losion, baby oil, bedak, krim, dan sediaan untuk bayi lainnya.sediaan untuk bayi lainnya.

2.2. Sediaan untuk mandi; bath oil, tablet, salt, buble bath, bath capsule, Sediaan untuk mandi; bath oil, tablet, salt, buble bath, bath capsule, dan sediaan untuk mandi lainnya.dan sediaan untuk mandi lainnya.

3.3. Sediaan untuk makeSediaan untuk make--up mata; eye brow pencil, eye liner, eye shadow, up mata; eye brow pencil, eye liner, eye shadow, eye makeeye make--up remover, mascara, dan sediaan makeup remover, mascara, dan sediaan make--up mata lainnya.up mata lainnya.

4.4. Sediaan wangiSediaan wangi--wangian; cologne dan toilet water, parfum, wangian; cologne dan toilet water, parfum, 4.4. Sediaan wangiSediaan wangi--wangian; cologne dan toilet water, parfum, wangian; cologne dan toilet water, parfum, powder(dusting dan talcum, tidak termasuk aftershave talc), dan powder(dusting dan talcum, tidak termasuk aftershave talc), dan sediaan wangisediaan wangi--wangian lainnya.wangian lainnya.

5.5. Sediaan rambut (bukan cat rambut); hair conditioner, hair spray Sediaan rambut (bukan cat rambut); hair conditioner, hair spray (aerosol fixative), hair straightener, hair rinse (bukan cat), tonik rambut, (aerosol fixative), hair straightener, hair rinse (bukan cat), tonik rambut, hair dressing dan hair grooming aid lainnya, wave set, serta sediaan hair dressing dan hair grooming aid lainnya, wave set, serta sediaan rambut lainnya.rambut lainnya.

6.6. Sediaan pewarna rambut(cat rambut); hair dye dan colour, hair Sediaan pewarna rambut(cat rambut); hair dye dan colour, hair rinse(cat), shampoo rambut (cat), hair tint, hair colour spray, hair rinse(cat), shampoo rambut (cat), hair tint, hair colour spray, hair lightener with colour, hair bleach, dan sediaan pewarna rambut lainnya.lightener with colour, hair bleach, dan sediaan pewarna rambut lainnya.


7.7. Sediaan makeSediaan make--up ( bukan untuk mata); blusher, face powder, foundation, up ( bukan untuk mata); blusher, face powder, foundation, pewarna kaki dan badan, lipstick, makepewarna kaki dan badan, lipstick, make--up base, rouge, makeup base, rouge, make--up fixative, dan up fixative, dan sediaan makesediaan make--up lainnya.up lainnya.

8.8. Sediaan untuk kebersihan mulut; mouth wash, pasta gigi, breath freshener, dan Sediaan untuk kebersihan mulut; mouth wash, pasta gigi, breath freshener, dan sediaan untuk kebersihan mulut lainnya.sediaan untuk kebersihan mulut lainnya.

9.9. Sediaan kuku; basecoat dan undercoat, cuticle softener, nail cream dan lotion, Sediaan kuku; basecoat dan undercoat, cuticle softener, nail cream dan lotion, nail extender, nail polish dan enamel remover, dan sediaan kuku lainnya.nail extender, nail polish dan enamel remover, dan sediaan kuku lainnya.

10.10. Sediaan untuk kebersihan badan; sabun dan deterjen mandi, deodorant (under Sediaan untuk kebersihan badan; sabun dan deterjen mandi, deodorant (under arm), douche, feminine hygiene, deodorant, dan sediaan untuk kebersihan arm), douche, feminine hygiene, deodorant, dan sediaan untuk kebersihan badan lainnya.badan lainnya.

11.11. Sediaan cukur; afterSediaan cukur; after--shave lotion, beard softener, talcum untuk pria, preshave lotion, beard softener, talcum untuk pria, pre--shave shave lotion, krim cukur (aerosol brushless dan lather ), sabun cukur, dan sediaan lotion, krim cukur (aerosol brushless dan lather ), sabun cukur, dan sediaan cukur lainnya.cukur lainnya.

12.12. Sediaan perawat kulit; pembersih (cold cream, cleansing liquid dan pad), Sediaan perawat kulit; pembersih (cold cream, cleansing liquid dan pad), depilatory, perawat kulit untuk muka, badan dan tangan ( tidak termasuk depilatory, perawat kulit untuk muka, badan dan tangan ( tidak termasuk sediaan cukur), bedak dan spray untuk kaki, pelembab, perawat kulit yang sediaan cukur), bedak dan spray untuk kaki, pelembab, perawat kulit yang dipakai pada malam hari, masker, skion freshener, wrinkle smoothing remover, dipakai pada malam hari, masker, skion freshener, wrinkle smoothing remover, dan sediaan kulit lainnya.dan sediaan kulit lainnya.

PENGGUNAAN PENGGUNAAN

WHITENING AGENTWHITENING AGENT

1.1. SKIN WHITENINGSKIN WHITENING2.2. TOOTH WHITENINGTOOTH WHITENING

SKIN WHITENINGSKIN WHITENING

Skin whitening bertujuan:Skin whitening bertujuan: untuk mendapatkan penampilan kulit untuk mendapatkan penampilan kulit

lebih cerah (tujuan kosmetik secara lebih cerah (tujuan kosmetik secara lebih cerah (tujuan kosmetik secara lebih cerah (tujuan kosmetik secara komersial)komersial)

untuk pengobatan klinis dari gangguan untuk pengobatan klinis dari gangguan pigmen (pigmentary disorders) seperti pigmen (pigmentary disorders) seperti melasma or postinflammatory melasma or postinflammatory hyperpigmentation . hyperpigmentation .

SKIN WHITENINGSKIN WHITENING

Many of them are known as competitive Many of them are known as competitive inhibitors of tyrosinase, the key enzyme inhibitors of tyrosinase, the key enzyme in melanogenesis. Others inhibit the in melanogenesis. Others inhibit the maturation of this enzyme or the maturation of this enzyme or the transport of pigment granules transport of pigment granules (melanosomes) from melanocytes to (melanosomes) from melanocytes to surrounding keratinocytes surrounding keratinocytes

PENDAHULUANPENDAHULUAN

Pada kulit, melanosit berada di lapisan basal Pada kulit, melanosit berada di lapisan basal yang memisahkan dermis dan epidermis. yang memisahkan dermis dan epidermis. Satu melanosit dikelilingi oleh sekitar 36 Satu melanosit dikelilingi oleh sekitar 36 keratinosit. Bersama, mereka membentuk keratinosit. Bersama, mereka membentuk unit melanin yang disebut epidermis. Melanin unit melanin yang disebut epidermis. Melanin unit melanin yang disebut epidermis. Melanin unit melanin yang disebut epidermis. Melanin yang diproduksi dan disimpan di dalam yang diproduksi dan disimpan di dalam melanosit di kompartemen melanosomal melanosit di kompartemen melanosomal diangkut melalui dendrit ke keratinosit diangkut melalui dendrit ke keratinosit overlay. Pigmen melanin merupakan polimer overlay. Pigmen melanin merupakan polimer yang diproduksi di dalam melanosomes dan yang diproduksi di dalam melanosomes dan disintesis dari tirosin Ldisintesis dari tirosin L--asam amino yang asam amino yang dikonversi oleh enzim tyrosinase.dikonversi oleh enzim tyrosinase.


Pembentukan melanin merupakan faktor Pembentukan melanin merupakan faktor penting pada warna kulit manusia. penting pada warna kulit manusia. Penghambatan pembentukan melanin dapat Penghambatan pembentukan melanin dapat mengakibatkan pengurangan kegelapan kulit. mengakibatkan pengurangan kegelapan kulit. mengakibatkan pengurangan kegelapan kulit. mengakibatkan pengurangan kegelapan kulit. Pembentukan melanin dalam tubuh manusia Pembentukan melanin dalam tubuh manusia berkurang dengan beberapa mekanisme, berkurang dengan beberapa mekanisme, termasuk antitermasuk anti--oksidasi, penghambatan oksidasi, penghambatan tirosinase langsung, penghambatan migrasi tirosinase langsung, penghambatan migrasi melanin dari sel ke sel dan aktivitas hormon, melanin dari sel ke sel dan aktivitas hormon, dll (Slominski et al., 2004).dll (Slominski et al., 2004).


Tirosinase merupakan enzim yang terkait Tirosinase merupakan enzim yang terkait dengan sintesis melanin dalam melanosit dan dengan sintesis melanin dalam melanosit dan mengkatalisis dua reaksi utama : mengkatalisis dua reaksi utama : monophenolase : hidroksilasi Lmonophenolase : hidroksilasi L--tirosin dan tirosin dan monophenolase : hidroksilasi Lmonophenolase : hidroksilasi L--tirosin dan tirosin dan diphenolase : oksidasi Ldiphenolase : oksidasi L--dopa (3,4dopa (3,4--dihydroxyphenylalanine). dihydroxyphenylalanine). Penghambatan tirosinase (monophenolase Penghambatan tirosinase (monophenolase dan diphenolase) akan menurunkan sintesis dan diphenolase) akan menurunkan sintesis melanin (Dubey dkk, 2006.). melanin (Dubey dkk, 2006.).

Targeting Tyrosinase as the Targeting Tyrosinase as the

Key Enzyme of Key Enzyme of

MelanogenesisMelanogenesisOne of the most obvious cellular targets One of the most obvious cellular targets for for depigmenting agents is the enzyme depigmenting agents is the enzyme tyrosinasetyrosinase. The scientific literature on . The scientific literature on tyrosinase inhibition shows that a large tyrosinase inhibition shows that a large tyrosinase inhibition shows that a large tyrosinase inhibition shows that a large majority of the work has been majority of the work has been conducted since 2000 and has mostly conducted since 2000 and has mostly been devoted to the search for new been devoted to the search for new depigmenting agents. Notably, many of depigmenting agents. Notably, many of these studies deal with these studies deal with tyrosinase tyrosinase inhibitorsinhibitors from natural sources and are from natural sources and are mostly of Asian origin mostly of Asian origin



MelanogenesisMelanogenesis

However, early pioneering work in the field However, early pioneering work in the field has been performed much earlier usinghas been performed much earlier using 44--hydroxyanisolehydroxyanisole. This compound could serve . This compound could serve as an as an alternative substrate for tyrosinase alternative substrate for tyrosinase as an as an alternative substrate for tyrosinase alternative substrate for tyrosinase causing depigmentation both causing depigmentation both in vivo in vivo and and in in vitrovitro ..Since this and various other substituted Since this and various other substituted phenolic compoundphenolic compound can generate potentially can generate potentially toxic quinone products they were used in toxic quinone products they were used in various studies aimed at the induction of various studies aimed at the induction of toxicity mediated by tyrosinase in melanoma toxicity mediated by tyrosinase in melanoma cells cells



MelanogenesisMelanogenesis Work on synthetic and natural tyrosinase inhibitors Work on synthetic and natural tyrosinase inhibitors

has been recently reviewed in several papers . The has been recently reviewed in several papers . The tyrosinase inhibitorstyrosinase inhibitors can be classified as can be classified as competitive, competitive, uncompetitive, mixed type and nonuncompetitive, mixed type and non--competitive competitive inhibitors.inhibitors.inhibitors.inhibitors.

Sifat penghambatan tirosinase dapat diungkapkan Sifat penghambatan tirosinase dapat diungkapkan dengan mengukur kinetika inhibisi enzim dengan mengukur kinetika inhibisi enzim menggunakan Lineweavermenggunakan Lineweaver--Burk plot dengan Burk plot dengan berbagai konsentrasi Lberbagai konsentrasi L--dopa sebagai substrat. Hal ini dopa sebagai substrat. Hal ini dapat dilihat pada contoh ekstrak polifenol dari dapat dilihat pada contoh ekstrak polifenol dari Acerola (Barat India cherry) atau turunan chalcone Acerola (Barat India cherry) atau turunan chalcone terisolasi dari Morus nigra (hitam murbei) (penelitian terisolasi dari Morus nigra (hitam murbei) (penelitian terkini Hanamura terkini Hanamura et al. et al. and Zhang and Zhang et alet al ) [11,12]. ) [11,12].




Knowledge of the type of inhibition may Knowledge of the type of inhibition may be important in order to achieve better be important in order to achieve better skin lightening effects since skin lightening effects since combined combined treatments may result in synergistic treatments may result in synergistic effectseffects. This has been shown in case of . This has been shown in case of the the competitive tyrosinase inhibitor, competitive tyrosinase inhibitor, arbutinarbutin and the and the noncompetitive inhibitor, noncompetitive inhibitor, aloesinaloesin [9,13] [9,13]



MelanogenesisMelanogenesisA 2009 paper by Chang states that a A 2009 paper by Chang states that a large majority of large majority of

tyrosinase inhibitors show reversible inhibitiontyrosinase inhibitors show reversible inhibition [10]. [10]. In In irreversible inhibition, covalent binding with the irreversible inhibition, covalent binding with the enzyme may cause its inactivation by altering the enzyme may cause its inactivation by altering the active site of the enzyme and/or by conformational active site of the enzyme and/or by conformational active site of the enzyme and/or by conformational active site of the enzyme and/or by conformational changes to the protein moleculechanges to the protein molecule. Irreversible . Irreversible inhibition may also occur via the soinhibition may also occur via the so--called called suicide suicide inhibitioninhibition mechanism as described in the model by mechanism as described in the model by Land Land et al. [14].et al. [14]. Also, two Also, two 88--hydroxy isoflavoneshydroxy isoflavonesisolated from soygerm koji showed suicide inhibition isolated from soygerm koji showed suicide inhibition of tyrosinase and have been tested with promising of tyrosinase and have been tested with promising results in an results in an in vivo in vivo assay with 60 volunteers [10]. assay with 60 volunteers [10].




Thus, exact knowledge on enzyme inhibition Thus, exact knowledge on enzyme inhibition mechanisms is helpful for designing new mechanisms is helpful for designing new whitening products based on targeting the whitening products based on targeting the key enzyme of melanogenesis, tyrosinasekey enzyme of melanogenesis, tyrosinase. . key enzyme of melanogenesis, tyrosinasekey enzyme of melanogenesis, tyrosinase. . Although tyrosinase plays a major role in Although tyrosinase plays a major role in melanin synthesis, one should realize that the melanin synthesis, one should realize that the regulation of skin pigmentation exists at regulation of skin pigmentation exists at various levels and therefore, different modes various levels and therefore, different modes of interference are possible. There are of interference are possible. There are indications that combined approaches could indications that combined approaches could be more successful than targeting tyrosinase be more successful than targeting tyrosinase only.only.



MelanogenesisMelanogenesisIn Table 1 we summarize the In Table 1 we summarize the large number of studies using large number of studies using tyrosinase inhibitors from tyrosinase inhibitors from natural sources that have natural sources that have natural sources that have natural sources that have appeared, mostly in the last appeared, mostly in the last decade. In many of the decade. In many of the investigations, the active investigations, the active ingredients from extracts of ingredients from extracts of various species have been various species have been isolated and identified. isolated and identified.

Table 1. Compounds selected as tyrosinase inhibitors by extraction from natural sources and the (possible) isolation and characterization of the active ingredients.

SourceSourceCompounds (type)Compounds (type) Mode of action tested*Mode of action tested*

Refs.Refs.TITI commentscomments

Chouji and YakuchiChouji and Yakuchiextracts, crude drugsextracts, crude drugs

eugenol, yakuchinone A, ferulic eugenol, yakuchinone A, ferulic acid,acid,curcumin and yakuchinone Bcurcumin and yakuchinone B

TI (c)TI (c) [18][18]

Anacardium occidentale,Anacardium occidentale,cashew fruitcashew fruit

66--[8(Z), [8(Z), 11(11(ZZ), 14), 14--pentadecatrienyl]pentadecatrienyl]--

TI (c)TI (c) [19][19]cashew fruitcashew fruit pentadecatrienyl]pentadecatrienyl]--

salicylic acid and salicylic acid and 55--[8(Z), [8(Z), 11(11(ZZ), ), 1414--pentadecatrienyl]resorcinolpentadecatrienyl]resorcinol

Bolivian medicinalBolivian medicinalplants, plants, BuddleiaBuddleiacoriacea, Gnaphaliumcoriacea, Gnaphaliumcheiranthifolium, cheiranthifolium, andandScheelea princeps.Scheelea princeps.

phenolicphenolic TITI [20][20]

Artocarpus gomezianus.Artocarpus gomezianus. among eight other compoundsamong eight other compoundsnorartocarpetin (5) and resveratrolnorartocarpetin (5) and resveratrol(8) were isolated(8) were isolated

5,8 were5,8 weremostmostpotent TIpotent TI

[21][21]




Artocarpus incisusArtocarpus incisus flavonoids, stilbenes and related 4flavonoids, stilbenes and related 4--substituted resorcinolssubstituted resorcinols

TITI 44--substitutedsubstitutedrecorcinolrecorcinolincreases TIincreases TI(c)(c)

[15][15]

StryphnodendronStryphnodendron unknownunknown strong TIstrong TI TI TI [22][22]StryphnodendronStryphnodendronbarbatimao, Portulacabarbatimao, Portulacapilosa, Carinianapilosa, Carinianabrasiliensis, Entadabrasiliensis, Entadaafricana africana and and Pros opisPros opisafricana. africana. Five plants out Five plants out ofof67 tropical plants67 tropical plants

unknownunknown strong TIstrong TI TI TI comparablecomparableto to Morus albaMorus albaas positiveas positivecontrolcontrol

[22][22]

Pulsatilla cernuaPulsatilla cernua 3,43,4--dihydroxycinnamic acid (1) 4dihydroxycinnamic acid (1) 4--hydroxyhydroxy--33--methoxycinnamic acid methoxycinnamic acid (2)(2)

2 > other TI2 > other TI> 1> 11,2 (nc)1,2 (nc)

[23][23]

galls of galls of Rhus javanicaRhus javanica Tannic acidTannic acid TITI -- [24][24]


Sophora flavescensSophora flavescens prenylated flavonoids; kuraridin,prenylated flavonoids; kuraridin,kurarinone and norkurarinolkurarinone and norkurarinol

strong strong TI >TI >KAKA

C8 and C5C8 and C5substitutionissubstitutionisessential foressential forTITI

[16][16]

SourceSourceCompounds (type)Compounds (type) Mode of action tested*Mode of action tested* Refs.Refs.

TITI commentscomments

Sophora flavescensSophora flavescens sophoraflavanone G, kuraridin, sophoraflavanone G, kuraridin, andandkurarinonekurarinone

TI > KATI > KA [25][25]

Veratrum patulumVeratrum patulum hydroxystilbene compounds;hydroxystilbene compounds;resveratrol, oxyresveratrol, and resveratrol, oxyresveratrol, and theirtheiranalogsanalogs

potent potent TITI cellulasecellulase

treatmenttreatmentimproved TIimproved TI

[17][17]

Phellinus linteusPhellinus linteus cerebroside B (1), protocatecerebroside B (1), protocate--chualdehyde (2), 5chualdehyde (2), 5--hydroxymethylhydroxymethyl--22--furaldehyde (HMF) (3), succinic furaldehyde (HMF) (3), succinic acidacid(4), fumaric acid (5)(4), fumaric acid (5)

2,3 TI2,3 TI2 > 32 > 32 (c)2 (c)3 (nc)3 (nc)

[26][26]




Ecklonia stolonifera.Ecklonia stolonifera.edible brown alga out of edible brown alga out of 1717seaweed extractsseaweed extracts

phloroglucinol derivativesphloroglucinol derivatives[phloroglucinol (1), eckstolonol [phloroglucinol (1), eckstolonol (2),(2),eckol (3), phlorofucofuroeckol A eckol (3), phlorofucofuroeckol A (4),(4),

1,2 TI (c)1,2 TI (c)33--5 (nc)5 (nc)

TI similar toTI similar toarbutinarbutin

[27][27]

(4),(4),and dieckol (5)].and dieckol (5)].

39 seashore plant species,39 seashore plant species,Japan: Japan: Hibiscus tiliaceus,Hibiscus tiliaceus,Carex pumila, Carex pumila, andandGarcinia subellipticaGarcinia subelliptica

GS contained 2 biflavonoids; GS contained 2 biflavonoids; 22RR,3,3SS--5,7,4',5'',7'',3''',4'''5,7,4',5'',7'',3''',4'''--heptahydroxyheptahydroxy--flavanone[3flavanone[3--8''] flavone (1) and8''] flavone (1) and5,7,4',5'',7'',3''',4'''5,7,4',5'',7'',3''',4'''--heptahydroxy[3heptahydroxy[3--8'']8'']biflavanone (2)biflavanone (2)

both strongboth strongTITI1 > KA1 > KA

[28][28]

Glycyrrhiza uralensisGlycyrrhiza uralensisGlycyrrhiza inflateGlycyrrhiza inflateLicoriceLicorice

liquiritin(1), licuraside (2),liquiritin(1), licuraside (2),isoliquiritin(3), liquiritigenin(4) isoliquiritin(3), liquiritigenin(4) andandlicochalcone A (5)licochalcone A (5)

2,3 and 52,3 and 5potent TI potent TI (c)(c)

[29][29]




Trifolium balansaeTrifolium balansae three steroids, stigmastthree steroids, stigmast--55--eneene--33beta,26beta,26--diol (2), stigmastdiol (2), stigmast--55--eneene--33--olol(3) and campesterol (4)(3) and campesterol (4)

2,3 and 42,3 and 4potent TIpotent TI2 > 3,42 > 3,4

[30][30]

Amberboa ramosa Amberboa ramosa JafriJafri cycloartane type triterpenoids; eightcycloartane type triterpenoids; eightcompounds identified. 3,21,22,23compounds identified. 3,21,22,23--

7 most7 mostpotent TIpotent TI

SAR studiesSAR studies [31][31]compounds identified. 3,21,22,23compounds identified. 3,21,22,23--tetrahydroxycycloarttetrahydroxycycloart--24 (3 24 (3 1),25(26)1),25(26)--diene (cmpd. 7)diene (cmpd. 7)

potent TIpotent TI> KA> KA

Sake leesSake lees triacylglycerols; triolein (1) andtriacylglycerols; triolein (1) andtrilinolein (2)trilinolein (2)

TI 1,2 (nc)TI 1,2 (nc)TI 2 > 1TI 2 > 1

PI in PI in E coli E coli (2)(2)

[32][32]

Garcinia kolaGarcinia kola screening 21 families of medicinalscreening 21 families of medicinalplants from West and Central Africa.plants from West and Central Africa.5 extracts selected with G. kola5 extracts selected with G. kolashowing good TI; five biflavanonesshowing good TI; five biflavanonesidentifiedidentified

TI > 60%TI > 60%IC50 > KAIC50 > KA

[33][33]




Marrubium velutinum Marrubium velutinum andandMarrubium cylleneumMarrubium cylleneum

Screening of 45 metabolites.Screening of 45 metabolites.Flavonoids (1), phenylethanoidFlavonoids (1), phenylethanoidglycosides (2), phenolic acids (3)glycosides (2), phenolic acids (3)

1,21,2moderatemoderateTI, 3 < 2TI, 3 < 2

[34][34]

Lichen species;Lichen species; unknownunknown TI (1)TI (1)antioxidant,antioxidant, [35,3[35,3Lichen species;Lichen species;Graphidaceae family(1)Graphidaceae family(1)

Usnea ghattensis (2),Usnea ghattensis (2),Heterodermia podocarpa,Heterodermia podocarpa,Arthothelium awasthii Arthothelium awasthii (3)(3)and and Parmotrema Parmotrema tinctorumtinctorum

unknownunknown TI (1)TI (1)3030--78%78% antioxidant,antioxidant,

antimicrobial,antimicrobial,antityrosinaseantityrosinaseIC50 (2,3)IC50 (2,3)similar or lesssimilar or lessthan other TIsthan other TIs

[35,3[35,36]6]

Sophora flavescensSophora flavescens sophoraflavanone G (1), sophoraflavanone G (1), kurarinonekurarinone(2) and kurarinol (3)(2) and kurarinol (3)

strong TIstrong TI1,2 (nc)1,2 (nc)3 (c)3 (c)

1,21,2antibacterialantibacterial3 PI in SB3 PI in SBMMS on 3MMS on 3

[37][37]




50 crude drugs50 crude drugsGlycyrrhiza glabra, Glycyrrhiza glabra, MorusMorusalba, Syzygiumalba, Syzygiumaromaticum, Citrus auaromaticum, Citrus au--

yesyesAll < KAAll < KA

[38][38]

aromaticum, Citrus auaromaticum, Citrus au--rantifolia, Cypreae morantifolia, Cypreae mo--neta, Punica granatum neta, Punica granatum andandCitrus aurantiumCitrus aurantiumGanoderma lucidumGanoderma lucidum yesyes [39][39]Arbutus andrachneArbutus andrachne Arbutin, hydroquinone, Arbutin, hydroquinone, --

sitosterolsitosteroland ursolic acid present in extractsand ursolic acid present in extracts

yesyes [40][40]

Morus alba Morus alba L. and L. and MorusMorusrotundiloba rotundiloba KoidzKoidzMulberryMulberry

betulinic acid (present)betulinic acid (present) yesyes antiantiinflammatoryinflammatory

[41][41]


SourceSource Compounds (type)Compounds (type) Mode of action tested*Mode of action tested* Refs.Refs.TITI commentscomments

Guioa villosaGuioa villosa sesquiterpene diglycosides;sesquiterpene diglycosides;crenulatosides E, F and G ( 1 crenulatosides E, F and G ( 1 -- 3)3)betulin ( 14), lupeol ( 15) andbetulin ( 14), lupeol ( 15) andsoyacerebroside I ( 16)soyacerebroside I ( 16)

nono

strong TIstrong TI

[42][42]

Broussonetia kazinoki.Broussonetia kazinoki. 1 ,31 ,3--diphenylpropanes: kazinol C (1),diphenylpropanes: kazinol C (1),D (2), F (3), broussonin C (4), kazinolD (2), F (3), broussonin C (4), kazinolS (5) and kazinol T (6)S (5) and kazinol T (6)

1,31,3--5 (c)5 (c)4; max TI4; max TI

--

--

[43][43]

S (5) and kazinol T (6)S (5) and kazinol T (6)Artocarpus heterophyllusArtocarpus heterophyllus 15 compounds.15 compounds.

norartocarpetin (4) and artocarpesinnorartocarpetin (4) and artocarpesin(6)(6)

yesyes5 cmpds >5 cmpds >KAKA

--

--

[44,45][44,45]

Paeonia sufruticosaPaeonia sufruticosa kaempferol (I), quercetin (II),kaempferol (I), quercetin (II),mudanpioside B (III), benzoylmudanpioside B (III), benzoyl--oxypaeoniflorin (IV), mudanpiosideoxypaeoniflorin (IV), mudanpiosideH (V), and pentagalloylH (V), and pentagalloyl----DD--glucoseglucose(VI)(VI)

yesyesI to V (c)I to V (c)VI (nc)VI (nc)

--

--

[46][46]

TI; tyrosinase inhibition, (c) competitive mode (nc) non competitive mode of inhibition. SB; Streptomyces bikiniensis [47]. MMS; molecular modeling studies on TI. SAR; structure activity relationship. PI; pigment inhibition.

Different Modes of Reducing Melanin Different Modes of Reducing Melanin

Production in Melanocytes and SkinProduction in Melanocytes and Skin

In Table 2, we sum up a large number In Table 2, we sum up a large number of studies that describe new whitening of studies that describe new whitening agents from natural sources with some agents from natural sources with some extra information on their mode of extra information on their mode of action besides the inhibition of action besides the inhibition of tyrosinase. Next to tyrosinase inhibition tyrosinase. Next to tyrosinase inhibition (TI) the extracts or their isolated active (TI) the extracts or their isolated active components were demonstrated to components were demonstrated to exhibit pigment inhibition (PI). exhibit pigment inhibition (PI).

Table 2. New whitening agents from natural sources and their mode of action as tyrosinase inhibitor (TI), inhibitor of pigment synthesis (PI) or by other mechanisms. Azelaic acid, Kojic acid, Arbutin and Aloesin are often used as positive skin whitening agents.

SourceSourceCompounds (type)Compounds (type) Mode of action tested(*)(**)Mode of action tested(*)(**)

Refs.Refs.TITI PIPI otherother

PityrosporumPityrosporumovaleovale

Azelaic acid; C9Azelaic acid; C9--dicarboxylic aciddicarboxylic acid

yesyes yesyes -- [75][75]

Aspergillus nigerAspergillus niger Kojic acid; 5Kojic acid; 5--hydroxyhydroxy--22--Yes Yes (c,m)(c,m)

-- -- [76,77[76,77]]Aspergillus nigerAspergillus niger

and and AspergillusAspergilluspenicilliumpenicillium

hydroxyhydroxy--22--(hydroxymethyl)(hydroxymethyl)----pyronepyrone

(c,m)(c,m) ]]

ArctostaphylosArctostaphylosuvauva--ursiursibearberrybearberry

Arbutin; Arbutin; hydroquinonehydroquinoneglucoside glucoside --dd--gluconopyranosidegluconopyranoside

yesyes(c,m,nc)(c,m,nc)

-- -- [13,78[13,78]][79][79]

Aloe veraAloe vera Aloesin; CAloesin; C--glycosylatedglycosylatedchromonechromone

yes (nc)yes (nc) -- -- [9,13,[9,13,80]80]




Artocarpus incisusArtocarpus incisus(best of)(best of)23 heart wood23 heart woodspecies from Papuaspecies from PapuaNew Guinea.New Guinea.

(+)(+)--dihydromorin,dihydromorin,chlorophorin, (+)chlorophorin, (+)--norartocarpanone, 4norartocarpanone, 4--prenylprenyl--oxyresveratrol, artocarbene,oxyresveratrol, artocarbene,artocarpesin and isoartoartocarpesin and isoarto--

yesyes KAKA yesyes(B 16 and(B 16 andGP)GP)

-- [81][81]

New Guinea.New Guinea. artocarpesin and isoartoartocarpesin and isoarto--carpesincarpesin

Morus albaMorus albaRheum undulatumRheum undulatum 1. Oxyresveratrol1. Oxyresveratrol2. Hydroxystilbene2. Hydroxystilbene

yes > KAyes > KA(nc)(nc)yesyes

-- 1. no effect on1. no effect onexpression orexpression orsynthesissynthesis

[82][82]

Morus albaMorus alba Mulberroside F (moracin MMulberroside F (moracin M--6, 3'6, 3'--didi--OO--betabeta--DD--glucopyranosideglucopyranoside

yesyes yesyes(melan(melan--a)a)

mild antimild anti--oxidant SOoxidant SOscavenger KA antimutagenicantimutagenic [84][84]




Ramulus moriRamulus mori(young twigs of(young twigs ofMorus alba)Morus alba)

2,3',4,5'2,3',4,5'--tetrahydroxytetrahydroxy--stilbene (2stilbene (2--oxyresveratrol)oxyresveratrol)

yes (c)yes (c) yesyes(GP + (GP + UV)UV)

no effect no effect onon

expression expression oror

[85][85]

oxyresveratrol)oxyresveratrol) ororsynthesissynthesisnonnon--toxictoxic

Glycyrrhiza Glycyrrhiza glabraglabraLicorice extractLicorice extract

glabrene and 2',4',4glabrene and 2',4',4--tritri--hydroxychalconehydroxychalcone

yesyes yesyes [86][86]

Grape seedGrape seed proanthocyanidinproanthocyanidin yesyes yesyes(B 16,(B 16,GP + GP + UV)UV)

antioxidantantioxidantactivity,activity,8OHdG8OHdG

[56][56]




AspergillusAspergillusfumigatus fumigatus andandSaccharomycesSaccharomycescerevisiaecerevisiae

melanin degrading melanin degrading enzymesenzymes

-- -- [70][70]

cerevisiaecerevisiaeCarthamusCarthamustinctoriustinctoriussafflower seedssafflower seeds

1) 1) NN--feruloylserotonin,2) feruloylserotonin,2) NN--((pp--coumaroyl)serotonin, coumaroyl)serotonin, andand3) acacetin3) acacetin

yes, 1,2 yes, 1,2 >>arbutinarbutin

yesyes(SB, B (SB, B 16).16).1,2 >1,2 >arbutinarbutin

[49][49]




GlycyrrhizaGlycyrrhizauralensisuralensis

Glycyrrhisoflavone (1) andGlycyrrhisoflavone (1) andglyasperin C(2)glyasperin C(2)

yesyes yesyes(B 16) 1 > 2(B 16) 1 > 2

[87][87]

Punica granatumPunica granatumPomegranatePomegranate

ellagic acidellagic acid yes yes ArbArb yes (GP +yes (GP +UV) UV) AAAA

[57][57]

Fish, PoultryFish, Poultry vitamin B3 derivative,vitamin B3 derivative,niacinamideniacinamide

nono nono MT inh.MT inh.Mc/Kc cocult.Mc/Kc cocult.

[53][53]niacinamideniacinamide Mc/Kc cocult.Mc/Kc cocult.

CTCT

Piper longumPiper longum piperlongumininepiperlonguminine nono yesyes(B16 +(B16 +msh)msh)

Tyr mRNA red.Tyr mRNA red.cAMP pathwaycAMP pathwayvia MITF inh.via MITF inh.

[88,89][88,89]

Angelica dahuricaAngelica dahurica isoimperatorinisoimperatorinimperatorinimperatorin

nono yesyes(B 16)(B 16)

Tyr protein +Tyr protein +mRNA red.mRNA red.

[90][90]

ArtocarpusArtocarpuslakoochalakoochaheartwoodheartwood

oxyresveratroloxyresveratrol yesyes NdNd CT (femaleCT (femalevolunteers) >volunteers) >KA > licoriceKA > licorice

[60][60]




AstragalusAstragalustaschkendicustaschkendicus

askendoside Baskendoside B yesyes NdNd [91][91]

SpatholobusSpatholobussuberectus suberectus DunnDunn(Leguminosae)(Leguminosae)

Butin (most effectiveButin (most effectivecompound)compound)

yesyes yesyes(nHEM)(nHEM)

Tyr,TrpTyr,Trp-- 1 1 andandTrpTrp--2 2 reducedreduced

[64][64]

(Leguminosae)(Leguminosae)Chinese herbChinese herb

reducedreduced(WB,qPCR)(WB,qPCR)

Sophora Sophora japonicajaponicaand and SpatholobusSpatholobussuberectus suberectus out out ofof25 Chinese 25 Chinese HerbsHerbs

high phenolic content, high phenolic content, e.g.,e.g.,gallic acidgallic acid


AO activityAO activity(DPPH)(DPPH)

[92][92]




Galla ChinensisGalla ChinensisRadix Radix ClematidisClematidisout of 90 out of 90 ChineseChineseHerbsHerbs

unknownunknown yesyes yesyes(Mel(Mel--ab,ab,melanmelan--a,a,melanmelan--a/a/SP 1SP 1cocult.)cocult.)

Effects on Effects on Tyr,Tyr,TrpTrp--1 and 1 and TrpTrp--22expressionexpression

[52][52]

HerbsHerbs cocult.)cocult.)KaempferiaKaempferiapanduratapandurata chalcone compounds,chalcone compounds,isopanduratin A and 4isopanduratin A and 4--

hydroxypanduratin Ahydroxypanduratin A

yes > yes > PTUPTU

yesyes(melan(melan--a) a) >>PTUPTU

Tyr proteinTyr proteinreducedreduced

[93][93]

Corn branCorn bran Polyamine conjugates, Polyamine conjugates, N,N'N,N'--dicoumaroylputrescinedicoumaroylputrescine(DCP), (DCP), NN--pp--coumaroylcoumaroyl--N'N'--feruloylputrescine feruloylputrescine (CFP),(CFP),and and N,N'N,N'--diferuloyldiferuloyl--putrescine (DFP)putrescine (DFP)

yesyesDCP > DCP > AAAA

yesyes(B 16)(B 16)DFP > DFP > ArbArb

AO activityAO activity(DPPH)(DPPH)

[94][94]



Refs.Refs.TITI PIPI TITI

PodocarpusPodocarpusmacrophyllusmacrophyllus

2,32,3--dihydrodihydro--4',4'''4',4'''--didi--OO--methylamentoflavonemethylamentoflavone


TrpTrp--2 mRNA2 mRNAreducedreduced

[95][95]

Longan seedLongan seed corilagin, gallic acid andcorilagin, gallic acid andellagic acid or otherellagic acid or otherphenolic/flavonoidphenolic/flavonoidglycosides and ellagitanninsglycosides and ellagitannins

yesyes n.d.n.d. AO activityAO activity(DPPH and(DPPH andORAC assays)ORAC assays)

[71][71]

Gastrodia elataGastrodia elataBlumeBlumeOrchidaceaeOrchidaceae

(synthetic) (synthetic) pp--hydroxybenzylhydroxybenzylalcoholalcohol

yes (Irrev)yes (Irrev) yesyes(B 16,(B 16,mouse MCmouse MC--KC cocult.)KC cocult.)

AO; radicalAO; radicalscavengerscavenger

[51,96][51,96]

Sophora flavescensSophora flavescens 1) kurarinol, 2) kuraridinol,1) kurarinol, 2) kuraridinol,and 3) trifolirhizinand 3) trifolirhizin

yesyes1,2 > KA1,2 > KA1,2 (nc)1,2 (nc)

yes (B 16)yes (B 16) [97][97]

Cucumis sativusCucumis sativus LuteinLutein nono yes (B 16)yes (B 16) Tyr proteinTyr proteinreducedreduced

[98][98]

LespedezaLespedezacyrtobotryacyrtobotrya

Haginin AHaginin A yes (nc)yes (nc) yesyes(melan(melan--a)a)GP (+UV)GP (+UV)zebra fishzebra fish

MITF, Tyr,MITF, Tyr,TrpTrp-- 1 reduced.1 reduced.Erk inducedErk induced

[59][59]



Refs.Refs.TITI PIPI TITI

MalpighiaMalpighiaemarginataemarginataAcerola fruitAcerola fruit

cyanidincyanidin--33--alphaalpha--OO--rhamnoside. pelargonidinrhamnoside. pelargonidin--33----OO--rhamnosiderhamnoside

yesyes yes (B 16)yes (B 16)GP (+UV)GP (+UV)

[11][11]

Coccoloba uviferaCoccoloba uviferaSea grapeSea grape

unknownunknown yesyes(nHEM)(nHEM)

AO; reducesAO; reducesILIL--1alpha,1alpha,TNFTNF--alpha andalpha andalphaalpha--MSH inMSH in

[74][74]

alphaalpha--MSH inMSH innHEM + UVnHEM + UV

SalicorniaSalicorniaherbacea,herbacea,halophytehalophyte

yesyes yes (B 16)yes (B 16) AO activityAO activity [99][99]

A llium A llium speciesspeciessuch as garlic andsuch as garlic andonions.onions.

11--propylmercaptanpropylmercaptan yesyes KAKA yes yes KAKA [100][100]

WillughbeiaWillughbeiacoriaceacoriaceaPhyllanthusPhyllanthusurinaria urinaria out of 14out of 14medicinal plantsmedicinal plantsCentralCentralKalimantanKalimantan

unknownunknown yesyesyesyes

yes (B 16)yes (B 16)yes (B16)yes (B16)

AO assayAO assayDPPHDPPH

[101][101]




Rhus Ghinensis;Rhus Ghinensis;Chinese gallsChinese galls

3 Gallotannins; 2,3,4,63 Gallotannins; 2,3,4,6--tetratetra--OO--galloylgalloyl--DD--glucopyranose,glucopyranose,1 ,2,3,61 ,2,3,6--tetratetra--OO--galloylgalloyl----DD--glucopyranose, and 1,2,3,4,6glucopyranose, and 1,2,3,4,6--pentapenta--OO--galloylgalloyl----DD--glucopyranoseglucopyranose

yes (nc)yes (nc) YesYes(B 16 + UVA;(B 16 + UVA;MSH)MSH)

[102][102]

Rhus succedaneaRhus succedanea 10'(Z)10'(Z)--heptadecenylheptadecenyl-- yes > HQyes > HQ yes > HQyes > HQ [103][103]Rhus succedaneaRhus succedanea 10'(Z)10'(Z)--heptadecenylheptadecenyl--hydroquinonehydroquinone

yes > HQyes > HQ yes > HQyes > HQ(B 16)(B 16)

[103][103]

PolygonumPolygonumcuspidatum.cuspidatum.Paris polyp hyllaParis polyp hyllaVitex negundoVitex negundo

Physcion (anthraquinone +Physcion (anthraquinone +anthraquinone analog)anthraquinone analog)(+)(+)--LyoniresinolLyoniresinol

yes yes KAKAyes > KAyes > KAyes > KAyes > KA

n.d.n.d.n.d.n.d.n.d,n.d,

Good skinGood skinpermeationpermeation

[10,104][10,104][105][105]

RaspberryRaspberry TilirosideTiliroside yesyes Yes (B 16)Yes (B 16) >Arb>Arb [106][106]ErigeronErigeronbreviscapusbreviscapusChinese herbChinese herb

(2Z,8Z)(2Z,8Z)--matricaria acidmatricaria acidmethyl estermethyl ester

nono yes (B 16, elanyes (B 16, elan--a > Arba > Arb

Tyr proteinTyr proteinreduced?reduced?

[107][107]

Alpinia galangaAlpinia galangaand and CurcumaCurcumaaromaticaaromaticamedicinal plantsmedicinal plants

eugenol and curcuminoidseugenol and curcuminoidspossible active ingredientspossible active ingredients

yesyes yes (G361 mayes (G361 macells + UVA)cells + UVA)

AO defenceAO defence [108][108]




Grape seedGrape seed oligomericoligomericproanthocyanidinsproanthocyanidins

-- yes, nHEM +yes, nHEM +UVUV

effects oneffects onTE, TrpTE, Trp--11and Trpand Trp--22expressionexpressionAO activityAO activity

[65][65]

* Modes of action tested; TI; tyrosinase inhibition, (c)competitive (u) uncompetitive (nc)non-competitive and (m) mixed mode; PI; pigment inhibition, SB; Streptomyces bikiniensis,B 16 or other melanoma cultures, melan-a mouse melanocytes, nHEM; normal humanepidermal melanocytes, SEM; skin equivalent model, ()-msh; ()-melanocyte stimulatinghormone, UV; ultraviolet, GP; guinea pig + msh or uv induced pigmentation; CT; tested inclinical trial. * * Comparison of effects on tyrosinase inhibition (TI) and pigmentationinhibition (PI) are mostly done in comparison to Arbutin (Arb), Kojic acid (KA) Ascorbic Acid(AA) and phenylthiourea (PTU). Other modes of action; AO; antioxidant; TE; tyrosinaseexpression (mRNA), MT; melanosome transport; 8OHdg = 8 hydroxy deoxy guanosine.

Cosmetic Use of (natural) Cosmetic Use of (natural)

Agents for Skin WhiteningAgents for Skin Whitening

In cosmetic formulations In cosmetic formulations hydroquinone (HQ)hydroquinone (HQ) has been has been widely used as an effective whitening agent but it has widely used as an effective whitening agent but it has been been banned recently because of serious safety banned recently because of serious safety concerns: its use has been connected with concerns: its use has been connected with mutagenicity and the increased incidence of mutagenicity and the increased incidence of mutagenicity and the increased incidence of mutagenicity and the increased incidence of ochronosis in Africanochronosis in African countries. Other compounds countries. Other compounds often used are often used are kojic acid, arbutin and azelaic acidkojic acid, arbutin and azelaic acid (see (see top of Table 2). top of Table 2). Arbutin Arbutin is a is a glycosylated form of HQglycosylated form of HQthat is present in bearberry extracts but it can also be that is present in bearberry extracts but it can also be synthesized from HQ by glucosidation. A new synthesized from HQ by glucosidation. A new derivative, derivative, deoxyarbutindeoxyarbutin was prepared by removal of all was prepared by removal of all hydroxyl groups from the glucose side chain of arbutin hydroxyl groups from the glucose side chain of arbutin and showed much lower cytotoxicity than arbutin and showed much lower cytotoxicity than arbutin [126,127]. [126,127].

Table 3. Limited selection of whitening products available on the market with some information on active ingredients.

CompanyCompany ProductProduct IngredientsIngredients Documentation; Documentation; in Vitro/in Vivo in Vitro/in Vivo EffectEffectRevitolRevitol Skin Skin

BrightenerBrightenerArbutin, Lumiskin (diacetyl Arbutin, Lumiskin (diacetyl boldine),boldine),Z Whitener (new natural Z Whitener (new natural ingredient,ingredient,unknown) + vitamins A,C and unknown) + vitamins A,C and E andE and

Lumiskin TM: action on tyrosinaseLumiskin TM: action on tyrosinaseexpression based on principle described expression based on principle described bybyFuller 2000 [128]Fuller 2000 [128]E andE and

other natural extracts other natural extracts (antioxidants)(antioxidants)

Fuller 2000 [128]Fuller 2000 [128]http://naturalskincareformula.com/http://naturalskincareformula.com/

PremiumPremiumNaturalsNaturals

SkinbrightSkinbright Arbutin, Kojic Acid, Lemon Arbutin, Kojic Acid, Lemon ExtractExtract

www.whiterskin.com/www.whiterskin.com/


CompanyCompany ProductProduct IngredientsIngredients Documentation; Documentation; in Vitro/in Vivo in Vitro/in Vivo EffectEffectSisquocSisquoc LucedermLucederm Niacinamide, Niacinamide, --Arbutin, Kojic Arbutin, Kojic

Acid,Acid,Mulberry, Bearberry, Licorice, Mulberry, Bearberry, Licorice,

LemonLemon

www.whiterskin.com/www.whiterskin.com/[29,53,82,83][29,53,82,83]

LIBiolLIBiol SynerlightSynerlight Actinidia Chinensis Actinidia Chinensis (Kiwi) (Kiwi) http://www.gattefossecanada.ca/http://www.gattefossecanada.ca/LIBiolLIBiol SynerlightSynerlight Actinidia Chinensis Actinidia Chinensis (Kiwi) (Kiwi) Fruit,Fruit,Sop hora Angustifolia Sop hora Angustifolia RootRoot

http://www.gattefossecanada.ca/http://www.gattefossecanada.ca/

BayerBayerHealthCareHealthCare

MandresyMandresyextractextract

Buddleja axillaris Buddleja axillaris leaves; leaves; extract richextract richin orthocinnamic compounds in orthocinnamic compounds andandflavonoids, verbascoside & flavonoids, verbascoside & luteolinluteolin

TI (mushroom); PI (nHEM + UV); TI (mushroom); PI (nHEM + UV); reducesreducesdendricity; dendricity; in vivo in vivo brightening 8 brightening 8 volunteersvolunteers(Chromameter)(Chromameter)www. serdexwww. serdex--plantextracts.com: plantextracts.com: United StatesUnited StatesPatent Application 20090028969Patent Application 20090028969


CompanyCompany ProductProduct IngredientsIngredients Documentation; Documentation; in Vitro/in Vivo in Vitro/in Vivo EffectEffectCivant SkinCivant Skincarecare

MeladermMeladerm Kojic Acid, Kojic Acid, --Arbutin, Niacinamide,Arbutin, Niacinamide,Mulberry, Bearberry, Licorice, Mulberry, Bearberry, Licorice, TegoTegoCosmo C250, Gigawhite, LemonCosmo C250, Gigawhite, LemonJuice, EmblicaJuice, EmblicaTegoCosmo; a natural amino acidTegoCosmo; a natural amino acid

niacinamide, mulberry and licorice (refs.niacinamide, mulberry and licorice (refs.[29,53,82,83])[29,53,82,83])www.whiterskin.com/;www.whiterskin.com/;http://www.whiterskin.com/studies/cosmo.phttp://www.whiterskin.com/studies/cosmo.pdfdfhttp://www.whiterskin.com/studies/giga.pdfhttp://www.whiterskin.com/studies/giga.pdfTegoCosmo; a natural amino acidTegoCosmo; a natural amino acid

derivative that belongs to the class derivative that belongs to the class ofofguanidine compoundsguanidine compoundsGiga white :plant extracts from theGiga white :plant extracts from theSwiss alps; Swiss alps; Malva Sylvestris, Malva Sylvestris, MenthaMenthaPiperita, Primula Veris, AlchemillaPiperita, Primula Veris, AlchemillaVulgaris, Veronica Oficinalis,Vulgaris, Veronica Oficinalis,Melissa Oficinalis, AchilleaMelissa Oficinalis, AchilleaMillefoliumMillefolium

http://www.whiterskin.com/studies/giga.pdfhttp://www.whiterskin.com/studies/giga.pdf


CompanyCompany ProductProduct IngredientsIngredients Documentation; Documentation; in Vitro/in Vivo in Vitro/in Vivo EffectEffectJujuJujuCosmeticsCosmetics

TosekkiTosekkiwhiteningwhiteningcreamcream

Glycyrrhetinic acid, Ginseng,Glycyrrhetinic acid, Ginseng,Houttuynia, Houttuynia, Yeast, Coix, HorseYeast, Coix, HorseChestnut, Arica, Grape Leaf,Chestnut, Arica, Grape Leaf,Ypericum, Ypericum, Ivy, Witch Hazel, Ivy, Witch Hazel, SophoraSophoraRoot, Mulberry Bark, Peony Root, Mulberry Bark, Peony

Glycyrrhetinc acid; Sophora Root; Glycyrrhetinc acid; Sophora Root; PeonyPeonyRoot; Mulberry Bark ( refs.Root; Mulberry Bark ( refs.[25,29,38,46,82,83,86])[25,29,38,46,82,83,86])http://beautyknot.wordpress.com/200http://beautyknot.wordpress.com/2009/02/27/j9/02/27/jRoot, Mulberry Bark, Peony Root, Mulberry Bark, Peony

Root,Root,Japanese Angelica Root, Rose Japanese Angelica Root, Rose FruitFruitand other ingredients.and other ingredients.

9/02/27/j9/02/27/jujuuju--cosmeticscosmetics--tosekkitosekki--whiteningwhitening--cream/cream/

LipotecLipotec ChromabrigChromabrightht

dimetylmethoxy chromanyl dimetylmethoxy chromanyl palmitatepalmitate

TI (mushroom + human); PI (nHEM)TI (mushroom + human); PI (nHEM)photoprotective; photoprotective; in vivo in vivo brightening brightening 20 Asian20 Asianfemales (Chromameter) females (Chromameter) www.lipotec.comwww.lipotec.com ;;Patent; Patent; http://www.maxworth.co.th/max/pdfhttp://www.maxworth.co.th/max/pdf/ES291 %20Chromabriht.pdf/ES291 %20Chromabriht.pdf

AbbreviationsAA; Ascorbic Acid, ACTH; adrenocorticotropic hormone, AO; antioxidant, Arb;

Arbutin, bFGF; basic fibroblast growth factor, BMP; bone morphogenetic proteins, cAMP; cyclic AMP, CT; clinical trials, DNJ; 1-deoxynojirimycin, DPPH; 1,1-diphenyl-2-picrylhydrazyl, ET-1; endothelin-1, ERK; extracellular signal-regulated kinases, GP; guinea pig, HGF; hepatocyte growth factor, HQ; hydroquinone, IC50; half maximal

inhibitory concentration, Il1; interleukin 1, KA; kojic acid, L-DOPA; L-dihydroxyphenylalanine, MC 1 R; melanocortin- 1 receptor, MITF; microphtalmia

transcription factor, ()-msh; ()-melanocyte stimulating hormone, MT; melanosome transport;

nHEM; normal human epidermal melanocytes, 8OHdg = 8 hydroxy deoxy nHEM; normal human epidermal melanocytes, 8OHdg = 8 hydroxy deoxy guanosine, ORAC; oxygen radical absorbance capacity, PKA; protein kinase A, PKC;

protein kinase C, PPAR; peroxisome proliferator- activated receptor, PTU; phenylthiourea, SAR; structure activity relationship, sAPP; soluble N-terminal

ectodomain of the beta-amyloid precursor protein, SCF; stem cell factor, SEM; skin equivalent model, Sox; Sry-related HMG box, TE; tyrosinase expression, TI; tyrosinase

inhibition, (c); competitive mode, (nc); non competitive mode, (m); mixed mode of inhibition, TNF-; tumor necrosis factor-, TRP; tyrosinase related protein, UV;

ultraviolet, UVA; ultraviolet A, UVB; ultraviolet B, UVR; ultraviolet radiation.

Natural Skin Whitening Natural Skin Whitening

AgentAgent

1.1. ArbutinArbutin2.2. Kojic AcidKojic Acid3.3. AloesinAloesin4.4. Azelaic AcidAzelaic Acid4.4. Azelaic AcidAzelaic Acid5.5. Flavone,3',4',5,6,7,8Flavone,3',4',5,6,7,8--hexamethoxyhexamethoxy--

(7CI,8CI);Nobiletin (6CI)(7CI,8CI);Nobiletin (6CI)6.6. 4 4 -- Hydroxystilbene Hydroxystilbene 7.7. OxyresveratrolOxyresveratrol8.8. ArtocarpinArtocarpin

ARBUTINARBUTIN

IUPAC nameIUPAC name ((2R,3S,4S,5R,6S2R,3S,4S,5R,6S))--22--HydroxymethylHydroxymethyl--66-- (4(4--hydroxyphenoxy)oxanehydroxyphenoxy)oxane--3,4,53,4,5--trioltriol Other namesOther names ArbutosideArbutoside

Hydroquinone Hydroquinone --DD--glucopyranosideglucopyranoside Identifiers Identifiers CAS numberCAS number 497497--7676--77 Properties Properties Molecular formulaMolecular formula C12H16O7 C12H16O7 Molar massMolar mass 272.25 g mol1 272.25 g mol1 Melting pointMelting point 199.5199.5 C, 473C, 473 K, 391K, 391 FF

ARBUTINARBUTIN

ArbutinArbutin is both an is both an etherether and a and a glycosideglycoside; a glycosylated ; a glycosylated hydroquinonehydroquinoneextracted from extracted from bearberrybearberry plant in the genus plant in the genus ArctostaphylosArctostaphylos. It . It inhibitsinhibitstyrosinasetyrosinase and thus prevents the formation of and thus prevents the formation of melaninmelanin. Arbutin is . Arbutin is therefore used as a skintherefore used as a skin--lightening agent. Arbutin is found in lightening agent. Arbutin is found in wheatwheat, and , and is concentrated in is concentrated in pearpear skins. It is also found in skins. It is also found in Bergenia crassifoliaBergenia crassifolia..[1][1]

Skin lightening agentSkin lightening agent Skin lightening agentSkin lightening agent Bearberry extract is used in skin lightening treatments designed for long Bearberry extract is used in skin lightening treatments designed for long

term and regular use. An active agent in brands of skin lightening term and regular use. An active agent in brands of skin lightening preparations, it is more expensive than traditional skin lightening preparations, it is more expensive than traditional skin lightening ingredients like ingredients like hydroquinonehydroquinone, which is now banned in many countries., which is now banned in many countries.

In vitro studies of human In vitro studies of human melanocytesmelanocytes exposed to arbutin at exposed to arbutin at concentrations below 300 g/mL reported decreased tyrosinase activity concentrations below 300 g/mL reported decreased tyrosinase activity and melanin content with little evidence of cytotoxicity.and melanin content with little evidence of cytotoxicity.[2][2]

KOJIC ACID KOJIC ACID

IUPAC name5-Hydroxy-2-(hydroxymethyl)-4H-pyran-4-one5-Hydroxy-2-(hydroxymethyl)-4H-pyran-4-oneOther namesKojic acid, 5-Hydroxy-2-(hydroxymethyl)-4-pyrone, 2-Hydroxymethyl-5-hydroxy--pyroneIdentifiers CAS number 501-30-4

Properties Molecular formula C6H6O4Molar mass 142.11 g/mol Appearance Tan powder Melting point 152 - 155 CSolubility in water SlightAcidity (pKa) 9.40[1]

KOJIC ACIDKOJIC ACID

Kojic acid (C6H6O4; 5Kojic acid (C6H6O4; 5--hydroxyhydroxy--22--(hydroxymethyl)(hydroxymethyl)--44--pyrone) pyrone) is a is a chelationchelation agent produced by several species of fungi, agent produced by several species of fungi, especially especially Aspergillus oryzaeAspergillus oryzae, which has the Japanese , which has the Japanese common name common name kojikoji..[2][2] Kojic acid is a byKojic acid is a by--product in the product in the fermentation process of malting rice, for use in the fermentation process of malting rice, for use in the manufacturing of sake, the Japanese rice wine.[manufacturing of sake, the Japanese rice wine.[citation citation fermentation process of malting rice, for use in the fermentation process of malting rice, for use in the manufacturing of sake, the Japanese rice wine.[manufacturing of sake, the Japanese rice wine.[citation citation neededneeded] It is a mild inhibitor of the formation of pigment in ] It is a mild inhibitor of the formation of pigment in plant and animal tissues, and is used in food and cosmetics plant and animal tissues, and is used in food and cosmetics to preserve or change colors of substances.to preserve or change colors of substances.[3][3] It is used on It is used on cut fruits to prevent cut fruits to prevent oxidative browningoxidative browning, in , in seafoodseafood to to preserve pink and red colors, and in cosmetics to lighten preserve pink and red colors, and in cosmetics to lighten skin. Kojic acid also has antibacterial and antifungal skin. Kojic acid also has antibacterial and antifungal properties.properties.

It is also used in skin diseases like It is also used in skin diseases like melasmamelasma..[4][4]

ALOESINALOESIN

ALOESINALOESIN

CAS No.30861CAS No.30861--2727--9Chemical Name:ALOESIN9Chemical Name:ALOESIN Synonyms:ALOESIN;Aloeresin B;Aloe resin B;8Synonyms:ALOESIN;Aloeresin B;Aloe resin B;8----

DD--GlucopyranosylGlucopyranosyl--77--hydroxyhydroxy--55--methylmethyl--22--(2(2--oxopropyl)oxopropyl)--4H4H--11--benzopyranbenzopyran--44--one;2one;2--(2(2--oxopropyl)oxopropyl)--4H4H--11--benzopyranbenzopyran--44--one;2one;2--(2(2--Oxopropyl)Oxopropyl)--55--methylmethyl--77--hydroxyhydroxy--88--((--DD--glucopyranosyl)glucopyranosyl)--4H4H--11--benzopyranbenzopyran--44--one;4Hone;4H--11--BenzopyranBenzopyran--44--one, 8one, 8--.beta..beta.--DD--glucopyranosylglucopyranosyl--77--hydroxyhydroxy--55--methylmethyl--22--(2(2--oxopropyl)oxopropyl)--CBNumber:CB1959107CBNumber:CB1959107

Molecular Formula:C19H22O9Molecular Formula:C19H22O9 Formula Weight:394.374MOLFormula Weight:394.374MOL

AZELAIC ACIDAZELAIC ACID

IUPAC name[hide]IUPAC name[hide]nonanedioic acidIdentifiers CAS number 123-99-9

Properties Molecular formula C9H16O4 Molar mass 188.22 g mol1 Melting point109-111 C[1]Boiling point286 C at 100 mmHg[1]Solubility in water 2.14 g/L[2] Acidity (pKa) 4.550, 5.498[2] Pharmacology Bioavailability Very low Routes ofadministration Topical Eliminationhalf-life 12 hours


Azelaic acid is an Azelaic acid is an organic compoundorganic compound with the with the formula (CH2)7(CO2H)2. This saturated formula (CH2)7(CO2H)2. This saturated dicarboxylic aciddicarboxylic acid exists as a white powder. It is exists as a white powder. It is found in found in wheatwheat, , ryerye, and , and barleybarley. It is a component . It is a component found in found in wheatwheat, , ryerye, and , and barleybarley. It is a component . It is a component of a number of hair and skin conditioners.of a number of hair and skin conditioners.

Azelaic acid is industrially produced by the Azelaic acid is industrially produced by the ozonolysisozonolysis of of oleic acidoleic acid. The side product is . The side product is nonanoic acid. It is produced naturally by nonanoic acid. It is produced naturally by Malassezia furfurMalassezia furfur (also known as (also known as Pityrosporum Pityrosporum ovaleovale), a ), a yeastyeast that lives on normal that lives on normal skinskin. The . The bacterial degradation of nonanoic acid gives bacterial degradation of nonanoic acid gives azelaic acid.azelaic acid.


Azelaic acid is industrially produced by the Azelaic acid is industrially produced by the ozonolysisozonolysis of of oleic acidoleic acid. . The side product is nonanoic acid. It is produced naturally by The side product is nonanoic acid. It is produced naturally by Malassezia furfurMalassezia furfur (also known as (also known as Pityrosporum ovalePityrosporum ovale), a ), a yeastyeast that that lives on normal lives on normal skinskin. The bacterial degradation of nonanoic acid . The bacterial degradation of nonanoic acid gives azelaic acid.gives azelaic acid.

Azelaic acid is used to treat mild to moderate acne, both comedonal Azelaic acid is used to treat mild to moderate acne, both comedonal Azelaic acid is used to treat mild to moderate acne, both comedonal Azelaic acid is used to treat mild to moderate acne, both comedonal acne and inflammatory acne.acne and inflammatory acne.[6][6][7][7] It works in part by stopping the It works in part by stopping the growth of skin bacteria that cause acne, and by keeping skin pores growth of skin bacteria that cause acne, and by keeping skin pores clear.clear.[8][8] Azelaic acid is also used as a topical gel treatment for Azelaic acid is also used as a topical gel treatment for rosacearosacea, due to its ability to reduce inflammation., due to its ability to reduce inflammation.[7][7] Azelaic acid has Azelaic acid has been used for treatment of skin pigmentation including melasma been used for treatment of skin pigmentation including melasma and post inflammatory hyperpigmentation, particularly in those with and post inflammatory hyperpigmentation, particularly in those with darker skin types. It has been recommended as an alternative to darker skin types. It has been recommended as an alternative to hydroquinonehydroquinone (HQ).(HQ).[9][9] As a As a tyrosinasetyrosinase inhibitor, azelaic acid inhibitor, azelaic acid reduces synthesis of reduces synthesis of melaninmelanin..[10][10]


Brand namesBrand names AzClear Action (20% lotion, AzClear Action (20% lotion, Ego PharmaceuticalsEgo Pharmaceuticals), ),

Azelex (20% cream, Azelex (20% cream, AllerganAllergan), White Action cream ), White Action cream (20% cream,2% glycolic acid), (20% cream,2% glycolic acid), SynCareSynCare), Finacea ), Finacea (20% cream,2% glycolic acid), (20% cream,2% glycolic acid), SynCareSynCare), Finacea ), Finacea (15% gel, Intendis/Berlex Laboratories, subsidiaries (15% gel, Intendis/Berlex Laboratories, subsidiaries of of BayerBayer AG), Finevin (20% cream, Intendis/Berlex AG), Finevin (20% cream, Intendis/Berlex Laboratories), Skinoren (20% cream or 15% gel, Laboratories), Skinoren (20% cream or 15% gel, Intendis), and Azaclear (azelaic acid and Intendis), and Azaclear (azelaic acid and niacinamide, Epikinetics LLC).niacinamide, Epikinetics LLC).

Flavone,3',4',5,6,7,8Flavone,3',4',5,6,7,8--hexamethoxyhexamethoxy--

(7CI,8CI);Nobiletin (6CI)(7CI,8CI);Nobiletin (6CI)

Name:Name: 4H4H--11--BenzopyranBenzopyran--44--one,2one,2--(3,4(3,4--dimethoxyphenyl)dimethoxyphenyl)--5,6,7,85,6,7,8--tetramethoxytetramethoxy--

Molecular Formula:Molecular Formula: C21H22O8C21H22O8 Molecular Structure:Molecular Structure: CAS:CAS: 478478--0101--3 3 CAS:CAS: 478478--0101--3 3 Refractive index:Refractive index: 1.558 1.558 Molecular Weight: Molecular Weight: 402.39 402.39 Flash Point: Flash Point: 256.5256.5C C Flash Point: Flash Point: 256.5256.5C C Density:Density: 1.244g/cm3 1.244g/cm3 Boiling Point: Boiling Point: 587.9587.9Cat760mmHg Cat760mmHg

4 4 -- HydroxystilbeneHydroxystilbene

Molecular Formula:Molecular Formula:C14H12O C14H12O

Molecular Weight:Molecular Weight: Molecular Weight:Molecular Weight:196.249 g/mol 196.249 g/mol

Cas Number:Cas Number:65546554--9898--9 9

OxyresveratrolOxyresveratrol

IUPAC Name: IUPAC Name: 44--[(E)[(E)--22--(3,5(3,5--dihydroxyphenyl)ethenyl]benzenedihydroxyphenyl)ethenyl]benzene--1,31,3--dioldiol

Artocarpin Artocarpin

Inhibition of Melanin Biosynthesis for Skin Whitening AgentInhibition of Melanin Biosynthesis for Skin Whitening Agent

REFERENSIREFERENSI

1.1. Cooksey, C.J.; Garratt, P.J.; Land, E.J.; Pavel, S.; Ramsden, C.A.; Riley, P.A.; Smit, N.P. Evidence of the Cooksey, C.J.; Garratt, P.J.; Land, E.J.; Pavel, S.; Ramsden, C.A.; Riley, P.A.; Smit, N.P. Evidence of the indirect formation of the catecholic intermediate substrate responsible for the autoactivation kinetics of indirect formation of the catecholic intermediate substrate responsible for the autoactivation kinetics of tyrosinase. tyrosinase. J. Biol. Chem. J. Biol. Chem. 1997, 1997, 272, 272, 262262622626235.26235.

2.2. Riley, P.A. Hydroxyanisole depigmentation: Riley, P.A. Hydroxyanisole depigmentation: InIn--vitro vitro studies. studies. J. Pathol. J. Pathol. 1969, 1969, 97, 97, 193193206.206.3.3. Riley, P.A. Hydroxyanisole depigmentation: Riley, P.A. Hydroxyanisole depigmentation: InIn--vivo vivo studies. studies. J. Pathol. J. Pathol. 1969, 1969, 97, 97, 185185191.191.4.4. NaishNaish--Byfield, S.; Cooksey, C.J.; Latter, A.M.; Johnson, C.I.; Riley, P.A. Byfield, S.; Cooksey, C.J.; Latter, A.M.; Johnson, C.I.; Riley, P.A. In vitro In vitro assessment of the assessment of the

structurestructure--activity relationship of tyrosinaseactivity relationship of tyrosinase--dependent cytotoxicity of a series of substituted phenols. dependent cytotoxicity of a series of substituted phenols. Melanoma. Res. Melanoma. Res. 1991, 1991, 1, 1, 273273287.287.

5.5. Smit, N.P.; Peters, K.; Menko, W.; Westerhof, W.; Pavel, S.; Riley, P.A. Cytotoxicity of a selected series of Smit, N.P.; Peters, K.; Menko, W.; Westerhof, W.; Pavel, S.; Riley, P.A. Cytotoxicity of a selected series of substituted phenols towards cultured melanoma cells. substituted phenols towards cultured melanoma cells. Melanoma Res. Melanoma Res. 1992, 1992, 2, 2, 295295304.304.substituted phenols towards cultured melanoma cells. substituted phenols towards cultured melanoma cells. Melanoma Res. Melanoma Res. 1992, 1992, 2, 2, 295295304.304.

6.6. Friedman, M. Food browning and its prevention: An overview. Friedman, M. Food browning and its prevention: An overview. J. Agric. Food Chem. J. Agric. Food Chem. 1996, 1996, 44, 44, 63 163 1653.653.

7.7. Kim, Y.J.; Uyama, H. Tyrosinase inhibitors from natural and synthetic sources: Structure, inhibition Kim, Y.J.; Uyama, H. Tyrosinase inhibitors from natural and synthetic sources: Structure, inhibition mechanism and perspective for the future. mechanism and perspective for the future. Cell Mol. Life Sci. Cell Mol. Life Sci. 2005, 2005, 62, 62, 170717071723.1723.

8.8. Mcevily, A.J.; Iyengar, R.; Otwell, S. Sulfite alternative prevents shrimp melanosis. Mcevily, A.J.; Iyengar, R.; Otwell, S. Sulfite alternative prevents shrimp melanosis. Food Technol.Food Technol.Chicago Chicago 1991, 1991, 45, 45, 808086.86.

9.9. Parvez, S.; Kang, M.; Chung, H.S.; Bae, H. Naturally occurring tyrosinase inhibitors: Mechanism and Parvez, S.; Kang, M.; Chung, H.S.; Bae, H. Naturally occurring tyrosinase inhibitors: Mechanism and applications in skin health, cosmetics and agriculture industries. applications in skin health, cosmetics and agriculture industries. Phytother. Res. Phytother. Res. 2007, 2007, 21, 21, 805805816.816.

10.10. Chang, T.S. An updated review of tyrosinase inhibitors. Chang, T.S. An updated review of tyrosinase inhibitors. Int. J. Mol. Sci. Int. J. Mol. Sci. 2009, 2009, 10, 10, 244024402475.2475.11.11. Hanamura, T.; Uchida, E.; Aoki, H. SkinHanamura, T.; Uchida, E.; Aoki, H. Skin--lightening effect of a polyphenol extract from Acerolalightening effect of a polyphenol extract from Acerola12.12. (Malpighia emarginata DC.) fruit on UV(Malpighia emarginata DC.) fruit on UV--induced pigmentation. induced pigmentation. Biosci. Biotechnol. Biochem.Biosci. Biotechnol. Biochem.13.13. 2008, 2008, 72, 72, 321132113218.3218.14.14. Zhang, X.; Hu, X.; Hou, A.; Wang, H. Inhibitory effect of 2,4,2',4'Zhang, X.; Hu, X.; Hou, A.; Wang, H. Inhibitory effect of 2,4,2',4'--tetrahydroxytetrahydroxy--33--(3(3--methylmethyl--22--butenyl)butenyl)--

chalcone on tyrosinase activity and melanin biosynthesis. chalcone on tyrosinase activity and melanin biosynthesis. Biol. Pharm. Bull. Biol. Pharm. Bull. 2009, 2009, 32, 32, 868690.90.15.15. Jin, Y.H.; Lee, S.J.; Chung, M.H.; Park, J.H.; Park, Y.I.; Cho, T.H.; Lee, S.K. Aloesin and arbutin inhibit Jin, Y.H.; Lee, S.J.; Chung, M.H.; Park, J.H.; Park, Y.I.; Cho, T.H.; Lee, S.K. Aloesin and arbutin inhibit

tyrosinase activity in a synergistic manner via a different action mechanism. tyrosinase activity in a synergistic manner via a different action mechanism. Arch. Pharm. Res. Arch. Pharm. Res. 1999, 1999, 22, 22, 232232236.236.

REFERENSIREFERENSI

16.16. Land, E.J.; Ramsden, C.A.; Riley, P.A.; Stratford, M.R. Evidence consistent with the requirement of cresolase activity for suLand, E.J.; Ramsden, C.A.; Riley, P.A.; Stratford, M.R. Evidence consistent with the requirement of cresolase activity for suicicide ide inactivation of tyrosinase. inactivation of tyrosinase. Tohoku J. Exp. Med. Tohoku J. Exp. Med. 2008, 2008, 216, 216, 23 123 1238.238.

17.17. Shimizu, K.; Kondo, R.; Sakai, K. Inhibition of tyrosinase by flavonoids, stilbenes and related 4Shimizu, K.; Kondo, R.; Sakai, K. Inhibition of tyrosinase by flavonoids, stilbenes and related 4--substituted resorcinols: Strucsubstituted resorcinols: Structureture--activity investigations. activity investigations. Planta Med. Planta Med. 2000, 2000, 66, 66, 111115.15.

18.18. Son, J.K.; Park, J.S.; Kim, J.A.; Kim, Y.; Chung, S.R.; Lee, S.H. Prenylated flavonoids from the roots of Sophora flavescens Son, J.K.; Park, J.S.; Kim, J.A.; Kim, Y.; Chung, S.R.; Lee, S.H. Prenylated flavonoids from the roots of Sophora flavescens witwith h tyrosinase inhibitory activity. tyrosinase inhibitory activity. Planta Med. Planta Med. 2003, 2003, 69, 69, 559559561. Kim, D.H.; Kim, J.H.; Baek, S.H.; Seo, J.H.; Kho, Y.H.; Oh, T.K.; 561. Kim, D.H.; Kim, J.H.; Baek, S.H.; Seo, J.H.; Kho, Y.H.; Oh, T.K.; Lee, C.H. Enhancement of tyrosinase inhibition of the extract of Veratrum patulum using cellulase. Lee, C.H. Enhancement of tyrosinase inhibition of the extract of Veratrum patulum using cellulase. Biotechnol. Bioeng. Biotechnol. Bioeng. 2004, 2004, 87, 87, 849849854.854.

19.19. Shirota, S.; Miyazaki, K.; Aiyama, R.; Ichioka, M.; Yokokura, T. Tyrosinase inhibitors from crude drugs. Shirota, S.; Miyazaki, K.; Aiyama, R.; Ichioka, M.; Yokokura, T. Tyrosinase inhibitors from crude drugs. Biol. Pharm. Bull. Biol. Pharm. Bull. 1994, 1994, 17, 17, 266266269.269.

20.20. Kubo, I.; KinstKubo, I.; Kinst--Hori, I.; Yokokawa, Y. Tyrosinase inhibitors from Anacardium occidentale fruits. Hori, I.; Yokokawa, Y. Tyrosinase inhibitors from Anacardium occidentale fruits. J. Nat. Prod. J. Nat. Prod. 1994, 1994, 57, 57, 54554555 1.55 1.21.21. Kubo, I.; Yokokawa, Y.; KinstKubo, I.; Yokokawa, Y.; Kinst--Hori, I. Tyrosinase inhibitors from Bolivian medicinal plants. Hori, I. Tyrosinase inhibitors from Bolivian medicinal plants. J. Nat. Prod. J. Nat. Prod. 1995, 1995, 58, 58, 739739743.743.21.21. Kubo, I.; Yokokawa, Y.; KinstKubo, I.; Yokokawa, Y.; Kinst--Hori, I. Tyrosinase inhibitors from Bolivian medicinal plants. Hori, I. Tyrosinase inhibitors from Bolivian medicinal plants. J. Nat. Prod. J. Nat. Prod. 1995, 1995, 58, 58, 739739743.743.22.22. Likhitwitayawuid, K.; Sritularak, B.; DeLikhitwitayawuid, K.; Sritularak, B.; De--Eknamkul, W. Tyrosinase inhibitors from Artocarpus gomezianus. Eknamkul, W. Tyrosinase inhibitors from Artocarpus gomezianus. Planta Med. Planta Med. 2000, 2000, 66, 66,

275275277.277.23.23. Baurin, N.; Arnoult, E.; Scior, T.; Do, Q.T.; Bernard, P. Preliminary screening of some tropical plants for antiBaurin, N.; Arnoult, E.; Scior, T.; Do, Q.T.; Bernard, P. Preliminary screening of some tropical plants for anti--tyrosinase actityrosinase activity. vity. J. J.

Ethnopharmacol. Ethnopharmacol. 2002, 2002, 82, 82, 155155158.158.24.24. Lee, H.S. Tyrosinase inhibitors of Pulsatilla cernua rootLee, H.S. Tyrosinase inhibitors of Pulsatilla cernua root--derived materials. derived materials. J. Agric. Food Chem. J. Agric. Food Chem. 2002, 2002, 50, 50, 140014001403.1403.25.25. Kubo, I.; KinstKubo, I.; Kinst--Hori, I.; Nihei, K.; Soria, F.; Takasaki, M.; Calderon, J.S.; Cespedes, C.L. Tyrosinase inhibitors from galls ofHori, I.; Nihei, K.; Soria, F.; Takasaki, M.; Calderon, J.S.; Cespedes, C.L. Tyrosinase inhibitors from galls of Rhus Rhus

javanica leaves and their effects on insects. javanica leaves and their effects on insects. Z. Naturforsch. C. Z. Naturforsch. C. 2003, 2003, 58, 58, 719719725.725.26.26. Kim, S.J.; Son, K.H.; Chang, H.W.; Kang, S.S.; Kim, H.P. Tyrosinase inhibitory prenylated flavonoids from Sophora flavescens.Kim, S.J.; Son, K.H.; Chang, H.W.; Kang, S.S.; Kim, H.P. Tyrosinase inhibitory prenylated flavonoids from Sophora flavescens.

Biol. Pharm. Bull. Biol. Pharm. Bull. 2003, 2003, 26, 26, 134813481350.1350.27.27. Kang, H.S.; Choi, J.H.; Cho, W.K.; Park, J.C.; Choi, J.S. A sphingolipid and tyrosinase inhibitors from the fruiting body of Kang, H.S.; Choi, J.H.; Cho, W.K.; Park, J.C.; Choi, J.S. A sphingolipid and tyrosinase inhibitors from the fruiting body of

Phellinus linteus. Phellinus linteus. Arch. Pharm. Res. Arch. Pharm. Res. 2004, 2004, 27, 27, 742742750.750.28.28. Kang, H.S.; Kim, H.R.; Byun, D.S.; Son, B.W.; Nam, T.J.; Choi, J.S. Tyrosinase inhibitors isolated from the edible brown algaKang, H.S.; Kim, H.R.; Byun, D.S.; Son, B.W.; Nam, T.J.; Choi, J.S. Tyrosinase inhibitors isolated from the edible brown alga

Ecklonia stolonifera. Ecklonia stolonifera. Arch. Pharm. Res. Arch. Pharm. Res. 2004, 2004, 27, 27, 12261226 1232.1232.29.29. Masuda, T.; Yamashita, D.; Takeda, Y.; Yonemori, S. Screening for tyrosinase inhibitors among extracts of seashore plants andMasuda, T.; Yamashita, D.; Takeda, Y.; Yonemori, S. Screening for tyrosinase inhibitors among extracts of seashore plants and

identification of potent inhibitors from Garcinia subelliptica. identification of potent inhibitors from Garcinia subelliptica. Biosci. Biotechnol. Biochem. Biosci. Biotechnol. Biochem. 2005, 2005, 69, 69, 197197201.201.30.30. Fu, B.; Li, H.; Wang, X.; Lee, F.S.; Cui, S. Isolation and identification of flavonoids in licorice and a study of their inhiFu, B.; Li, H.; Wang, X.; Lee, F.S.; Cui, S. Isolation and identification of flavonoids in licorice and a study of their inhibitbitory effects ory effects

on tyrosinase. on tyrosinase. J. Agric. Food Chem. J. Agric. Food Chem. 2005, 2005, 53, 53, 7408740874 14. Sabudak, T.; Tareq Hassan, K.M.; Iqbal, C.M.; Oksuz, S. Potent 74 14. Sabudak, T.; Tareq Hassan, K.M.; Iqbal, C.M.; Oksuz, S. Potent tyrosinase inhibitors from Trifolium balansae. tyrosinase inhibitors from Trifolium balansae. Nat. Prod. Res. Nat. Prod. Res. 2006, 2006, 20, 20, 665665670.670.

31.31. Khan, M.T.; Khan, S.B.; Ather, A. Tyrosinase inhibitory cycloartane type triterpenoids from the methanol extract of the wholeKhan, M.T.; Khan, S.B.; Ather, A. Tyrosinase inhibitory cycloartane type triterpenoids from the methanol extract of the wholeplant of Amberboa ramosa Jafri and their structureplant of Amberboa ramosa Jafri and their structure--activity relationship. activity relationship. Bioorg. Med. Chem. Bioorg. Med. Chem. 2006, 2006, 14, 14, 93 893 8943.943.

REFERENSIREFERENSI

32.32. Jeon, H.J.; Noda, M.; Maruyama, M.; Matoba, Y.; Kumagai, T.; Sugiyama, M. Identification and kinetic study of tyrosinase Jeon, H.J.; Noda, M.; Maruyama, M.; Matoba, Y.; Kumagai, T.; Sugiyama, M. Identification and kinetic study of tyrosinase inhibitors found in sake lees. inhibitors found in sake lees. J. Agric. Food Chem. J. Agric. Food Chem. 2006, 2006, 54, 54, 9 8279 827 9833.9833.

33.33. Okunji, C.; Komarnytsky, S.; Fear, G.; Poulev, A.; Ribnicky, D.M.; Awachie, P.I.; Ito, Y.; Raskin, I. Preparative isolation aOkunji, C.; Komarnytsky, S.; Fear, G.; Poulev, A.; Ribnicky, D.M.; Awachie, P.I.; Ito, Y.; Raskin, I. Preparative isolation and nd identification of tyrosinase inhibitors from the seeds of Garcinia kola by highidentification of tyrosinase inhibitors from the seeds of Garcinia kola by high--speed counterspeed counter--current chromatography. current chromatography. J. J. Chromatogr. A Chromatogr. A 2007, 2007, 1151, 1151, 4545 50.50.

34.34. Karioti, A.; Protopappa, A.; Megoulas, N.; Skaltsa, H. Identification of tyrosinase inhibitors fromKarioti, A.; Protopappa, A.; Megoulas, N.; Skaltsa, H. Identification of tyrosinase inhibitors from35.35. Marrubium velutinum and Marrubium cylleneum. Marrubium velutinum and Marrubium cylleneum. Bioorg. Med. Chem. Bioorg. Med. Chem. 2007, 2007, 15, 15, 2708270827 14.27 14.36.36. Behera, B.C.; Adawadkar, B.; Makhija, U. TyrosinaseBehera, B.C.; Adawadkar, B.; Makhija, U. Tyrosinase--inhibitory activity in some species of theinhibitory activity in some species of the37.37. lichen family Graphidaceae. lichen family Graphidaceae. J. Herb. Pharmacother. J. Herb. Pharmacother. 2006, 2006, 6, 6, 555569.69.38.38. Behera, B.C.; Verma, N.; Sonone, A.; Makhija, U. Tissue culture of some lichens and screening of their antioxidant, Behera, B.C.; Verma, N.; Sonone, A.; Makhija, U. Tissue culture of some lichens and screening of their antioxidant,

antityrosinase and antibacterial properties. antityrosinase and antibacterial properties. Phytother. Res. Phytother. Res. 2007, 2007, 21, 21, 11591159 1170.1170.antityrosinase and antibacterial properties. antityrosinase and antibacterial properties. Phytother. Res. Phytother. Res. 2007, 2007, 21, 21, 11591159 1170.1170.39.39. Ryu, Y.B.; Westwood, I.M.; Kang, N.S.; Kim, H.Y.; Kim, J.H.; Moon, Y.H.; Park, K.H. Kurarinol, tyrosinase inhibitor isolated Ryu, Y.B.; Westwood, I.M.; Kang, N.S.; Kim, H.Y.; Kim, J.H.; Moon, Y.H.; Park, K.H. Kurarinol, tyrosinase inhibitor isolated

from the root of Sophora flavescens. from the root of Sophora flavescens. Phytomedicine. Phytomedicine. 2008, 2008, 15, 15, 612612618.618.40.40. Adhikari, A.; Devkota, H.P.; Takano, A.; Masuda, K.; Nakane, T.; Basnet, P.; SkalkoAdhikari, A.; Devkota, H.P.; Takano, A.; Masuda, K.; Nakane, T.; Basnet, P.; Skalko--Basnet, N. Screening of Nepalese crude Basnet, N. Screening of Nepalese crude

drugs traditionally used to treat hyperpigmentation: drugs traditionally used to treat hyperpigmentation: In vitro In vitro tyrosinase inhibition. tyrosinase inhibition. Int. J. Cosmet. Sci. Int. J. Cosmet. Sci. 2008, 2008, 30, 30, 353353360.360.41.41. Chien, C.C.; Tsai, M.L.; Chen, C.C.; Chang, S.J.; Tseng, C.H. Effects on tyrosinase activity by the extracts of Ganoderma Chien, C.C.; Tsai, M.L.; Chen, C.C.; Chang, S.J.; Tseng, C.H. Effects on tyrosinase activity by the extracts of Ganoderma

lucidum and related mushrooms. lucidum and related mushrooms. Mycopathologia Mycopathologia 2008, 2008, 166, 166, 117117 120.120.42.42. Issa, R.A.; Afifi, F.U.; Amro, B.I. Studying the antiIssa, R.A.; Afifi, F.U.; Amro, B.I. Studying the anti--tyrosinase effect of Arbutus andrachne L. extracts. tyrosinase effect of Arbutus andrachne L. extracts. Int. J. Cosmet. Sci. Int. J. Cosmet. Sci.

2008, 2008, 30, 30, 27 127 1276.276.43.43. Nattapong, S.; Omboon, L. A new source of whitening agent from a Thai Mulberry plant and its betulinic acid quantitation. Nattapong, S.; Omboon, L. A new source of whitening agent from a Thai Mulberry plant and its betulinic acid quantitation.

Nat. Prod. Res. Nat. Prod. Res. 2008, 2008, 22, 22, 727727734.734.44.44. Magid, A.A.; VoutquenneMagid, A.A.; Voutquenne--Nazabadioko, L.; Bontemps, G.; Litaudon, M.; Lavaud, C. Tyrosinase inhibitors and sesquiterpene Nazabadioko, L.; Bontemps, G.; Litaudon, M.; Lavaud, C. Tyrosinase inhibitors and sesquiterpene

diglycosides from Guioa villosa. diglycosides from Guioa villosa. Planta Med. Planta Med. 2008, 2008, 74, 74, 555560.60.45.45. Baek, Y.S.; Ryu, Y.B.; CurtisBaek, Y.S.; Ryu, Y.B.; Curtis--Long, M.J.; Ha, T.J.; Rengasamy, R.; Yang, M.S.; Park, K.H. Tyrosinase inhibitory effects of 1,3 Long, M.J.; Ha, T.J.; Rengasamy, R.; Yang, M.S.; Park, K.H. Tyrosinase inhibitory effects of 1,3

--diphenylpropanes from Broussonetia kazinoki. diphenylpropanes from Broussonetia kazinoki. Bioorg. Med. Chem. Bioorg. Med. Chem. 2009, 2009, 17, 17, 353541.41.46.46. Zheng, Z.P.; Cheng, K.W.; To, J.T.; Li, H.; Wang, M. Isolation of tyrosinase inhibitors from Artocarpus heterophyllus and useZheng, Z.P.; Cheng, K.W.; To, J.T.; Li, H.; Wang, M. Isolation of tyrosinase inhibitors from Artocarpus heterophyllus and use

of its extract as antibrowning agent. of its extract as antibrowning agent. Mol. Nutr. Food Res. Mol. Nutr. Food Res. 2008, 2008, 52, 52, 153015301538.1538.47.47. Zheng, Z.P.; Chen, S.; Wang, S.; Wang, X.C.; Cheng, K.W.; Wu, J.J.; Yang, D.; Wang, M. Chemical components and Zheng, Z.P.; Chen, S.; Wang, S.; Wang, X.C.; Cheng, K.W.; Wu, J.J.; Yang, D.; Wang, M. Chemical components and

tyrosinase inhibitors from the twigs of Artocarpus heterophyllus. tyrosinase inhibitors from the twigs of Artocarpus heterophyllus. J. Agric. Food Chem. J. Agric. Food Chem. 2009, 2009, 57, 57, 664966496655.6655.48.48. Ding, H.Y.; Lin, H.C.; Chang, T.S. Tyrosinase inhibitors isolated from the roots of Paeonia suffruticosa. Ding, H.Y.; Lin, H.C.; Chang, T.S. Tyrosinase inhibitors isolated from the roots of Paeonia suffruticosa. J. Cosmet. Sci. J. Cosmet. Sci. 2009, 2009,

60, 60, 347347--352.352.

REFERENSIREFERENSI

49.49. Tomita, K.; Oda, N.; Ohbayashi, M.; Kamei, H.; Miyaki, T.; Oki, T. A new screening method for melanin biosynthesis inhibitorsTomita, K.; Oda, N.; Ohbayashi, M.; Kamei, H.; Miyaki, T.; Oki, T. A new screening method for melanin biosynthesis inhibitorsusing Streptomyces bikiniensis. using Streptomyces bikiniensis. J. Antibiot. (Tokyo) J. Antibiot. (Tokyo) 1990, 1990, 43, 43, 160116011605.1605.

50.50. Briganti, S.; Camera, E.; Picardo, M. Chemical and instrumental approaches to treat hyperpigmentation. Briganti, S.; Camera, E.; Picardo, M. Chemical and instrumental approaches to treat hyperpigmentation. Pigment Cell Res. Pigment Cell Res. 2003, 2003, 16, 16, 101101110.110.

51.51. Roh, J.S.; Han, J.Y.; Kim, J.H.; Hwang, J.K. Inhibitory effects of active compounds isolated from safflower (Carthamus tinctoRoh, J.S.; Han, J.Y.; Kim, J.H.; Hwang, J.K. Inhibitory effects of active compounds isolated from safflower (Carthamus tinctoriurius s L.) seeds for melanogenesis. L.) seeds for melanogenesis. Biol. Pharm. Bull. Biol. Pharm. Bull. 2004, 2004, 27, 27, 197619761978.1978.

52.52. Smit, N.P.; Kolb, R.M.; Lentjes, E.G.; Noz, K.C.; van der Meulen, H.; Koerten, H.K.; Vermeer, B.J.; Pavel, S. Variations in Smit, N.P.; Kolb, R.M.; Lentjes, E.G.; Noz, K.C.; van der Meulen, H.; Koerten, H.K.; Vermeer, B.J.; Pavel, S. Variations in melanin formation by cultured melanocytes from different skin types. melanin formation by cultured melanocytes from different skin types. Arch. Dermatol. Res. Arch. Dermatol. Res. 1998, 1998, 290, 290, 342342349.349.

53.53. Liu, S.H.; Chu, I.M.; Pan, I.H. Effects of hydroxybenzyl alcohols on melanogenesis in melanocyteLiu, S.H.; Chu, I.M.; Pan, I.H. Effects of hydroxybenzyl alcohols on melanogenesis in melanocyte--keratinocyte cokeratinocyte co--culture and culture and monolayer culture of melanocytes. monolayer culture of melanocytes. J. Enzyme Inhib. Med. Chem. J. Enzyme Inhib. Med. Chem. 2008, 2008, 23, 23, 526526534.534.

54.54. Zhong, S.; Wu, Y.; SooZhong, S.; Wu, Y.; Soo--Mi, A.; Zhao, J.; Wang, K.; Yang, S.; JaeMi, A.; Zhao, J.; Wang, K.; Yang, S.; Jae--Ho, Y.; Zhu, X. Depigmentation of melanocytes by the Ho, Y.; Zhu, X. Depigmentation of melanocytes by the treatment of extracts from traditional Chinese herbs: A cell culture assay. treatment of extracts from traditional Chinese herbs: A cell culture assay. Biol. Pharm. Bull. Biol. Pharm. Bull. 2006, 2006, 29, 29, 194719471951.1951.

54.54. Zhong, S.; Wu, Y.; SooZhong, S.; Wu, Y.; Soo--Mi, A.; Zhao, J.; Wang, K.; Yang, S.; JaeMi, A.; Zhao, J.; Wang, K.; Yang, S.; Jae--Ho, Y.; Zhu, X. Depigmentation of melanocytes by the Ho, Y.; Zhu, X. Depigmentation of melanocytes by the treatment of extracts from traditional Chinese herbs: A cell culture assay. treatment of extracts from traditional Chinese herbs: A cell culture assay. Biol. Pharm. Bull. Biol. Pharm. Bull. 2006, 2006, 29, 29, 194719471951.1951.

55.55. Greatens, A.; Hakozaki, T.; Koshoffer, A.; Epstein, H.; Schwemberger, S.; Babcock, G.; Bissett, D.; Takiwaki, H.; Arase, S.; Greatens, A.; Hakozaki, T.; Koshoffer, A.; Epstein, H.; Schwemberger, S.; Babcock, G.; Bissett, D.; Takiwaki, H.; Arase, S.; Wickett, R.R.; Boissy, R.E. Effective inhibition of melanosome transfer to keratinocytes by lectins and niacinamide is reversWickett, R.R.; Boissy, R.E. Effective inhibition of melanosome transfer to keratinocytes by lectins and niacinamide is reversiblible. e. Exp. Dermatol. Exp. Dermatol. 2005, 2005, 14, 14, 498498 508.508.

56.56. Duval, C.; Smit, N.P.; Kolb, A.M.; Regnier, M.; Pavel, S.; Schmidt, R. Keratinocytes control the pheo/eumelanin ratio in cultDuval, C.; Smit, N.P.; Kolb, A.M.; Regnier, M.; Pavel, S.; Schmidt, R. Keratinocytes control the pheo/eumelanin ratio in cultureured d normal human melanocytes. normal human melanocytes. Pigment Cell Res. Pigment Cell Res. 2002, 2002, 15, 15, 440440 446.446.

57.57. NiNi--Komatsu, L.; Leung, J.K.; Williams, D.; Min, J.; Khersonsky, S.M.; Chang, Y.T.; Orlow, S.J. TriazineKomatsu, L.; Leung, J.K.; Williams, D.; Min, J.; Khersonsky, S.M.; Chang, Y.T.; Orlow, S.J. Triazine--based tyrosinase based tyrosinase inhibitors identified by chemical genetic screening. inhibitors identified by chemical genetic screening. Pigment Cell Res. Pigment Cell Res. 2005, 2005, 18, 18, 447447453.453.

58.58. Yamakoshi, J.; Otsuka, F.; Sano, A.; Tokutake, S.; Saito, M.; Kikuchi, M.; Kubota, Y. Lightening effect on ultravioletYamakoshi, J.; Otsuka, F.; Sano, A.; Tokutake, S.; Saito, M.; Kikuchi, M.; Kubota, Y. Lightening effect on ultraviolet--induced induced pigmentation of guinea pig skin by oral administration of a proanthocyanidinpigmentation of guinea pig skin by oral administration of a proanthocyanidin--rich extract from grape seeds. rich extract from grape seeds. Pigment Cell Res. Pigment Cell Res. 2003, 2003, 16, 16, 62962963 8.63 8.

59.59. Yoshimura, M.; Watanabe, Y.; Kasai, K.; Yamakoshi, J.; Koga, T. Inhibitory effect of an ellagic acidYoshimura, M.; Watanabe, Y.; Kasai, K.; Yamakoshi, J.; Koga, T. Inhibitory effect of an ellagic acid--rich pomegranate extract onrich pomegranate extract ontyrosinase activity and ultraviolettyrosinase activity and ultraviolet--induced pigmentation. induced pigmentation. Biosci. Biotechnol. Biochem. Biosci. Biotechnol.

Whitening Agent Presentation

Documents