Biological Activities of Paper Mulberry

Paper mulberry (Broussonetia papyrifera) is one of the most common skin-lightening agents in the beauty industry due to its strong anti-tyrosinase activity. It consists of various components, including flavonoids, tannins, alkaloids, phenols, saponins, coumarins, glycosides, and polysaccharides, which possess a wide range of pharmacological properties. Apart from its anti-tyrosinase activity, paper mulberry and its compounds exhibited anti-inflammatory, antioxidant, antimicrobial, antiviral, anticancer, antidiabetic, anticholinesterase, antigout, antinociceptive, and hepatoprotective effects. Phenols and flavonoids were demonstrated to be the main contributors to the biological activities of paper mulberry. Paper mulberry is widely applied in cosmetics for skin lightening and skin moisturizing purposes and shows potential for application in hair care products due to the hair nourishing effects. The safety of paper mulberry for topical application was proven in clinical studies.

paper mulberry;Broussonetia papyrifera;skin-lightening;tyrosinase;pharmacological activities

1. Chemical Composition of Paper Mulberry

Paper mulberry consists of various chemical constituents, with the main bioactive compounds including flavonoids, tannins, alkaloids, phenols, saponins, coumarins, glycosides, and polysaccharides [1][2][3][4][5][6][22,27,28,29,30,31]. These compounds are derived from different parts of the paper mulberry, such as the bark, roots, twigs, leaves, flowers, and fruits. Table 1 summarizes the major bioactive components found in paper mulberry.
Table 1.
Chemical composition of paper mulberry.

2. Biological Activities of Paper Mulberry and Its Components

Previous studies have demonstrated that paper mulberry and its components possess a wide range of biological activities, such as antityrosinase, anti-inflammatory, antioxidant, and antimicrobial effects, as listed below (Table 2).
Table 2.
Biological activities of paper mulberry.

Biological Activity

Part

Compound

Model

Dose

Detailed Effects

Reference

Antityrosinase

Leaf

n/a

In vitro

IC50 = 17.68 ± 5.3 μg/mL

Inhibit mushroom tyrosinase

[40][63]

(2R)-7,3′,4′-trihydroxy-6-prenylflavanone

Leaf

[7][32]

n/a

In vitro

3,3′,4′,5,7-pentahydroxyflavone

[8][33]

Broussonetones A-C

In vitro

3,4-dihydroxyisolonchocarpin

[

62

]

66.67~666.67 μg/mL

IC50 = 0.317 ~ 0.323 mM

Inhibit mushroom tyrosinase

Isogemichalcone C

[

39

]

[

62

]

Inhibit mushroom tyrosinase

[

41][64]

Leaf

[

37

][60]

[9][10][11][34,35,36]

Twig

Broussoflavonol F, 3,5,7,4′-tetrahydroxy-3′-(2-hydroxy-3-methylbut-3-enyl)flavone, uralenol, quercetin

In vitro

IC50 = 49.5~96.6 μM

Inhibit mushroom tyrosinase

[25][48]

3′-(3-methylbut-2-enyl)-3′,4′,7-trihydroxyflavane

Root

[8][9][11]][33,34[,3612],37[13],38[14,39]

Broussoflavonol B/F/H-K, papyriflavonol A, isolicofavonol, glycyrrhiza flavonol

In vitro

IC50 = 9.29~31.74 μM

Inhibit mushroom tyrosinase

[15

4-hydroxyisolonchocarpin

[9][10][11][13][34,35,36,38]

7,8-dihydroxy-6-(3-methylbut-2-en-1-yl)-2H-chromen-2-one

[15][40]

8-(1,1-dimethylallyl)-5′-(3-methylbut-2-enyl)-3′,4′,5,7-tetrahydroxyflanvonol

[7][8][[16][3211][12],33,36,37,41]

]

[

40

]

Brossoflurenone A

[16][41]

Brossoflurenone B

[16][41]

Betulin

[17][42]

Betulinic acid

[17][42]

Broussoaurone A

[18][43]

Broussochalcone A

[7][8][9][10]19][25,32,33,34[11][13][,3514,36],38[,39]

Broussochalcone B

[9][10][[13][3411][12],35,36,37

Anti-inflammatory

Bark

n/a

RAW264.7 cells

10~200 μg/mL

Inhibit NO and iNOS production

[42][24]

Bark

n/a

RAW264.7 cells

10~80 μg/mL

Inhibit production of NO, iNOS, TNF-α, and IL-1β

[43][65]

Fruit

8,11-octadecadienic acid, palmitic acid, linolenic acid, 8-octadecenoic

acid, stearic acid, oleic acid

RAW264.7 cells

6~100 μg/mL

Reduce NO production

[30][53]

Root

Broussoflavonol B, kazinol J

Mice, 3T3-L1 adipocytes

40 mg/kg,

3~40 μg/mL

Decrease TNF-α-induced inflammation by inhibiting the NF-κB pathway via AMPK activation

[44][66]

Root

(2R)-7,3′,4′-trihydroxy-6-prenylflavanone, broussochalcone C, broussoflavanonol A/B, kazinol V/W

RAW264.7 cells

2.5~40 μM

Inhibit production of NO, iNOS, COX-2, TNF-α, and IL-6

[7][32]

Root

Broussochalcone A

RAW264.7 cells

1~20 μM

Inhibit production of NO, iNOS, TNF-α, and IL-1β

[45][67]

Branch, twig

Kazinol M, broussoflavonol A/B

THP-1 cells

1 μM

Reduce production of IL-1β and TNF-α by suppressing NF-κB/AP-1 activation

[26][49]

Root

Broussoflavonol H

Jurkat cells

IC50 = 9.95 μM

Decrease IL-2 production

[15][40]

Root, fruit

Betulin, betulinic acid

Rat

0.6, 1, 2 g/kg

Reduce edema

[17][42]

,38]

Root

Broussochalcone A, papyriflavonol A

Rat, MH-S cells

200 mg/kg,

5~50 μg/mL

Combined with Lonicera japonica to inhibit the production of NO, TNF-α, and IL-6 in macrophages, reduce pleural cavity inflammation and bronchitis

[46][68]

Broussochalcone C

[

n/a

7][32]

Papyriflavonol A

Rat

12.5~50 mg/kg

Inhibit IgE-induced passive cutaneous anaphylaxis

[47][69]

Broussocoumarin A

[15][40]

Antioxidant

Leaf

4-Caffeoylquinic acid, 5-Caffeoylquinic acid, apigenin-7-O-glucuronide, isovitexin, luteolin-7-O-glucuronide, orientin, vitexin

1~10 mM

In vitro

Radical-scavenging activities in DPPH and ABTS assays

[36][59]

Broussoflavan A

[7][9][11][13][14][18][32,34,36,38,39,43]

Luteolin, luteoloside, orientin, isoorientin

10 μg/mL

In vitro

Radical-scavenging activities in DPPH and ABTS assays

[38][61]

Broussoflavanonol A

Leaf

[7][32]

Broussonetones A−C, apigenin, vitexin

IC50 = 43.89~107.7 μM

In vitro

Antioxidant effects in SOD-like effect assays

[37][60]

Broussoflavonol B

[7][11][15][32[,3616,40],

Root

41]

n/a

0.1~2.5 mg/mL

SH-SY5Y cells

Decrease extracellular

peroxide levels, improve activities of SOD, CAT, glutathione peroxidase, and glutathione reductase

[48][70]

Broussoflavonol C

[

Bark, wood

7][32]

Epicatechin, caffeic acid, coumaric acid, quercetin, kaempferol

10~50 mg/mL

In vitro

Superoxide anion radical and hydroxyl radical scavenging activities

[24][26]

Broussoflavonol F

[15][18][40,43]

Flower

n/a

0.5~5 mg/mL

In vitro

Scavenging activity of DPPH radical

[4][29]

Broussoflavonol G

Fruit

[18][43]

2-(4-hydroxyphenyl)propane-1,3-diol-1-O-β-D-glucopyranoside, 4-hydroxybenzaldehyde, 3,4-dihydroxybenzoic acid, arbutine, dihydroconiferyl alcohol, coniferyl alcohol, ferulic acid, p-coumaraldehyde, cis-syringin, cis-coniferin, erythro1-(4-hydroxyphenyl)glycerol, threo-1-(4-hydroxyphenyl)glycerol, curculigoside C/I

0.16~100 mM

SH-SY5Y cells

Scavenging activity of DPPH radical and neuroprotective effects

against H2O2-induced SY5Y cell injury

[27][50]

Broussoflavonol H

[15][40]

Branch, twig

Kazinol M, broussoflavonol A/B

THP-1 cells

1 μM

Reduce CAA values

[26][49]

Broussoflavonol I

[15][40]

Root

Broussochalcone A

RAW264.7 cells

1~20 μM

Inhibit production of NO, iNOS, TNF-α, and IL-1β

[45][67]

Broussoflavonol J

Root

[15][40]

Broussoflavan A, broussoflavonol F/G, broussoaurone A

In vitro

IC50 = 1.0~2.7 μM

Inhibit oxidative stress caused by Fe2+ in rat brain homogenate

[18][43]

Broussoflavonol K

[15][40]

Fruit

Chushizisins A−I, threo-1-(4-hydroxy-3-methoxyphenyl)-2-{4-[(E)-3-hydroxy-1-propenyl]-2-methoxyphenoxy}-1,3-propanediol, erythro-1-(4-hydroxy-3-methoxyphenyl)-2-{4-[(E)-3-hydroxy-1-propenyl]-2-methoxyphenoxy}-1,3-propanediol

PC12 cells

0.16~100 μM

Scavenging activity of DPPH radical and antioxidant effects

against H2O2-induced impairment in PC12 cells

[28][51]

Broussonin A

Whole plant

[7][32]

Lignins

In vitro

10~100 mg/L

Scavenging activity of DPPH radical

[49][71]

Broussonin B

Aerial part

[7][32]

n/a

Beef cattle

5~15% in food

Increase SOD concentration, total antioxidant capacity

[50][72]

Broussonol D

[7][32]

Aerial part

n/a

Dairy cow

5~15% in food

Increase the concentration of CAT, SOD, and TAC and decrease the serum concentration of 8-OHdG

[51][73]

Broussonol G

Leaf

[7][32]

n/a

Piglet

150, 300 g/t

Increase concentration of CAT, SOD, glutathione peroxidase

[52][74]

Daphnegiravan H

[7][32]

Anti-microbial

Leaf

n/a

In vitro

MIC = 1~7.5 mg/mL

Inhibit growth of bacteria (Enterococcus faecalis, Vibrio cholera, Bacillus subtilis, Pseudomonas aeruginosa, Klibsella pneumonia) and fungi (Aspergilus niger, A. flavus)

[53][75]

Glycyrrhiza flavonol A

Seed

[15][40]

Hexadecanoic acid, heptadecene-8-carbonic acid, caryophyllene

In vitro

0.125~1%

Antibacterial activity against Staphylococcus aureus, Proteus vulgaris, B. cereus, Enterobacter aerogenes

[34][57]

Isolicoflavonol

Aerial part

[15][40]

Daphnegiravan F, 5,7,3′,4′-tetrahydroxy-3-methoxy-8,5′-diprenylflavone

In vitro

MIC = 3.9~250 ppm

Anti-oral microbial effect against Gram-positive strains (Actinomyces naeslundii, A. viscosus, Streptococcus mutans, S. sanguinis, S. sorbrinus) and Gram-negative strains (Aggregatibacter actinomycetemcomitans, Fusobacterium nucleatum, Porphyromonas gingivalis)

[54][76]

Kazinol A

[7][9][11][12][13][32,34,36,37,38]

Root

Papyriflavonol A, kazinol B, broussochalcone A

In vitro

MIC = 12.5~45 μg/mL

Antifungal effect against Candida albicans and Saccharomyces cerevisiae, antibacterial activity against Escherichia coli, Salmonella typhimurium, S. epidermis, S. aureus

[19][25]

Kazinol B

Root

[7][9][[19][2511][13],32,34,36,38]

Papyriflavonol A

In vitro

MIC = 10~25 μg/mL

Antifungal effect against C. albicans and S. cerevisiae

[20][44]

Kazinol E

[9][11][34,36]

Fruit

Polysaccharides

In vitro

0.4~2.0 mg/mL

Antibacterial activity against E. coli, P. aeruginosa, B. subtilis, S. aureus

[33][56]

Kazinol F

[7][13][14

Root

][32,38,39]

Broussochalcone A/B, broussoflavan A, 3′-(3-methylbut-2-enyl)-3′,4′,7-trihydroxyflavane, 3,4-dihydroxyisolonchocarpin, 8-(1,1-dimethylallyl)-5′-(3-methylbut-2-enyl)-3′,4′,5,7-tetrahydroxyflanvonol, daphnegiravan I, kazinol A/B/E, 4-hydroxyisolonchocarpin, papyriflavonol A, broussoflavonol B

In vitro

IC50 = 0.7~54 μM

Inhibit bacterial neuraminidase

[11][36]

Kazinol J

[7][13][14][32,38,39]

Kazinol V

[7][32]

Antiviral

Root

Broussochalcone A/B, 4-hydroxyisolonchocarpin, papyriflavonol A (4), 3′-(3-methylbut-2-enyl)-3′,4,7-trihydroxyflavane, kazinol A/B/F/J, broussoflavan A

In vitro

IC50 = 9.2~66.2 μM

Inhibit papain-like protease

[13][38]

Anticancer

Bark

n/a

Kazinol W

[7][32]

Oleanolic acid

[17][42]

HT-29 cells

50~200 μg/mL

Induce apoptosis-related DNA fragmentation, increase the expression of p53, caspase 3, Bax, inhibit cell proliferation

[42][24]

Bark

Papyriflavonol A, broussoflavonol B, broussochalcone A, uralenol, 5,7,3′,4′-tetrahydroxy-3-methoxy-8,5′-diprenylflavone

MCF-7 cells

5~25 μM

Anti-proliferation effects on estrogen receptor-positive breast cancer MCF-7 cells

[22][46]

Papyriflavonol A

[11]25[12][14][15][,3616,37],39[19,40][20][,41,44]

Ursolic acid

[17][42]

Bark

3,4,5-trimethoxyphenyl-1-O-β-D-xylopyranosyl-β-D-glucopyranoside

[21][45]

4,5-dicaffeoylquinic acid

[21][45]

5,7,3′,4′-tetrahydroxy-3-methoxy-8,5′-diprenylflavone

[22][46]

5,7,3′,4′-tetrahydroxy-3-methoxy-8-geranylflavone

[22][46]

7,4′-dihydroxy-3′-prenylflavan

[23][47]

Broussochalcone A

[22][46]

Broussochalcone B

[23][47]

Broussoflavonol B

[22][23][46,47]

Bark, leaf, fruit

n/a

MCF-7, HeLa, HepG2 cells

31.25~1000 μg/mL

Cytotoxic activity against cancer cells

[55][77]

Root

Broussoflavonol F/H/I/K, isolicofavonol, glycyrrhiza flavonol A, papyriflavonol A

NCI-H1975, HepG2, MCF-7 cells

IC50 = 0.9~2.0 μM

Growth inhibition activity against three cancer cell lines

[15][40]

Root

Kazinol A

T24, T24R2 cells

 

Inhibit cell growth through G0/1 arrest mediated by a decrease in cyclin D1 and an increase in p21

[12][37]

n/a

Broussochalcone A

HEK293, HCT116, SW480, SNU475 cells

5~20 μM

Induce apoptosis in colon and liver cancer cells

[56][78]

n/a

Broussochalcone A

HepG2 cells

5 µM

Cytotoxic effects against human hepatoma HepG2 cells with activation of apoptosis-related proteins

[57][79]

Fruit

N-norchelerythrine, dihydrosanguinarine, oxyavicine, broussonpapyrine, nitidine, chelerythrine, liriodenine

BEL-7402, Hela cells

IC50 = 5.97~47.41 μg/mL

Inhibit cancer cell growth

[31][54]

Antidiabetic

Root

Broussoflavonol B, kazinol J

Mice

40 mg/kg

Improve glucose tolerance

Broussonin A

[23][47]

Broussonin B

[23][47]

Caffeic acid

[24][26]

Cathayanon H

[23][47]

Chlorogenic acid

[21][45]

cis-form-5-coffee acylchlorogenic acid

[21][45]

Coumaric acid

[24][26]

Cryptochlorogenic acid

[21][45]

Epicatechin

[24][26]

Glyasperin A

[23][47]

Isoliquiritigenin

[23][47]

Isoquercetin

[21][45]

Kaempferol

[24][26]

Marmesin

[23][47]

Papyriflavonol A

[22][46]

Quercetin

[24][25][26,48]

Uralenol

[22][46]

Vomifoliol

[23][47]

Branch/twig

(S)-8-methoxymarmesin

[26][49]

3,5,7,4′-tetrahydroxy-3′-(2-hydroxy-3-methylbut-3-enyl) flavone

[25][48]

5,7,3′,4′-tetrahydroxy-3-methoxy-8,5′-diprenylflavone

[26][49]

5,7,3′,4′-tetrahydroxy-3-methoxyflavone

[25][48]

5,7,3′,5′-tetrahydroxyflavanone

[25][48]

Brossoflurenone C

[26][49]

Broussin

[26][49]

Broussoflavonol A

[26][49]

Broussoflavonol B

[26][49]

Broussoflavonol F

[25][48]

[

44

]

[

66

]

Root

8-(1,1-dimethylallyl)-5′-(3-methylbut-2-enyl)-3′,4′,5,7-tetrahydroxyflanvonol, uralenol, 3,3′,4′,5,7-pentahydroxyflavone, broussochalcone A

In vitro

IC50 = 4.3~36.8 μM

Inhibit the activity of PTP1B

[8][33]

Root

Broussochalcone A/B, 3,4-Dihydroxyisolonchocarpin, 4-Hydroxyisolonchocarpin, 3′-(3-Methylbut-2-enyl)-3′,4′,7-trihydroxyflavane, kazinol A/B/E, 8-(1,1-Dimethylallyl)-5′-(3-methylbut-2-enyl)-3′,4′,5,7-tetrahydroxyflanvonol, papyriflavonol A, brossoflurenone A

In vitro

IC50 = 2.1~75.7 μM

Inhibit the activity of α-glucosidase

[10][35]

Anticholinesterase

Root

8-(1,1-Dimethylallyl)-5′-(3-methylbut-2-enyl)-3′,4′,5,7-tetrahydroxyflanvonol, papyriflavonol A, broussoflavonol B, brossoflurenone A/B

In vitro

IC50 = 0.5~24.7 μM

Inhibit human acetylcholinesterase and butyrylcholinesterase

[16][41]

Antigout

Root

3,4-dihydroxyisolonchocarpin, broussochalcone A

In vitro

IC50 = 0.6~1.8 μM

Inhibit the activity of xanthine oxidase

[9][34]

Antinociceptive

Root, fruit

Betulin, betulinic acid

Rat

1, 2 g/kg

Inhibit writhing responses

[17][42]

Hepatoprotective

Leaf

Polysaccharides

Mice

100~400 mg/kg

Improve acetaminophen-induced liver damage, reduce liver apoptosis, enhance the detoxification ability of the liver to acetaminophen

[5][30]

Fipsotwin

[26][49]

Isolicoflavonol

[25][48]

Isoliquiritigenin

[25][48]

Kazinol B

[26][49]

Kazinol N

[26][49]

Kazinol M

[26][49]

Kazinol Q

[26][49]

Luteolin

Root

Broussoflavonol B, kazinol J

Mice

40 mg/kg

Suppress hepatic steatosis by decreasing lipogenic gene expression and increasing AMPK phosphorylation

[25][48]

Marmesin

[26][49]

Papyriflavonol A

[25][48]

Quercetin

[25][48]

[

44

]

[

66

]

threo-dadahol A

[26][49]

threo-dadahol B

[26][49]

Uralenol

[25][48]

Fruit

2-(4-hydroxyphenyl) propane-1,3-diol-1-O-β-D-glucopyranoside

[27][50]

3,4-dihydroxybenzoic acid

[27][50]

3-[2-(4- hydroxyphenyl)-3-hydroxymethyl-2,3-dihydro-1-benzofuran-5-yl]propan-1-ol

[28][51]

4-hydroxybenzaldehyde

[27][50]

7-hydroxycoumarin

[29][52]

8,11-Octadecadienoic acid

[30][53]

8-Octadecenoic acid

[30][53]

Arbutine

[27][50]

Betulin

[17][42]

Betulinic acid

[17][42]

Broussonpapyrine

[31][32][54,55]

Chelerythrine

[31][54]

Chushizisin A

[28][51]

Chushizisin B

[28][51]

Chushizisin C

[28][51]

Chushizisin D

[28][51]

Chushizisin E

[28][51]

Chushizisin F

[28][51]

Chushizisin G

[28][51]

Chushizisin H

[28][51]

Chushizisin I

[28][51]

cis-coniferin

[27][50]

cis-syringin

[27][50]

Coniferyl alcohol

[27][50]

Curculigoside C

[27][50]

Curculigoside I

[27][50]

Dihydroconiferyl alcohol

[27][50]

Dihydrosanguinarine

[31][54]

Epicatechin

[29][52]

erythro-1-(4-hydroxy-3-methoxyphenyl)-2-{4-[(E)-3-hydroxy-1-propenyl]-2-methoxyphenoxy}-1,3-propanediol

[28][51]

erythro-1-(4-hydroxyphenyl) glycerol

[27][50]

Ferulic acid

[27][50]

Linolenic acid

[30][53]

Liriodenine

[31][54[32],55]

Nitidine

[31][54[32],55]

N-Norchelerythrine

[31][54]

Oleanolic acid

[17][42]

Oleic acid

[30][53]

Oxyavicine

[31][32][54,55]

Palmitic acid

[30][53]

p-coumaraldehyde

[27][50]

Polysaccharides

[33][56]

Protocatechuic acid

[29][52]

Stearic acid

[30][53]

threo-1-(4-hydroxy-3-methoxyphenyl)-2-{4-[(E)-3-hydroxy-1-propenyl]-2-methoxyphenoxy}-1,3-propanediol

[28][51]

threo-1-(4-hydroxyphenyl) glycerol

[27][50]

Ursolic acid

[17][42]

Seed

Caryophyllene

[34][57]

Heptadecene-8-carbonic acid

[34][57]

Hexadecanoic acid

[34][57]

Leaf

(+)-pinoresinol-4′-O-β-D-glucopyranosyl-4″-O-β-D-apiofuranoside

[35][58]

3,5,4′-trihydroxy-bibenzyl-3-O-β-D-glucoside

[35][58]

4-Caffeoylquinic acid

[36][59]

4-Feruloylquinic acid

[36][59]

5-Caffeoylquinic acid

[36][59]

Apigenin

[37][38][60,61]

Apigenin-6-C-β-D-glucopyranside

[35][58]

Apigenin-7-glucoside

[36][59]

Apigenin-7-O-glucuronide

[36][59]

Apigenin-7-O-β -D-glucoside

[38][61]

Broussonetone A

[37][60]

Broussonetone B

[37][60]

Broussonetone C

[37][60]

Broussoside A

[38][61]

Broussoside B

[38][61]

Broussoside C

[38][61]

Broussoside D

[38][61]

Broussoside E

[38][61]

Chrysoriol-7-O-β-D-glucoside

[38][61]

Cosmosiin

[35][58]

Coumaric acid

[38][61]

Dihydrosyringin

[38][61]

Flacourtin

[38][61]

Gentisoyl hexoside

[36][59]

Isoorientin

[38][61]

Isovitexin

[36][38][59,61]

Liriodendrin

[35][58]

Luteolin

[38][61]

Luteolin-7-O-glucuronide

[36][59]

Luteolin-7-O-β-D-glucopyranoside

[35][58]

Luteoloside

[38][61]

Orientin

[36][38][59,61]

Pinoresinol-4′-O-β-D-glucopyranoside

[38][61]

Poliothyrsoside

[38][61]

Polysaccharides

[5][30]

Syringaresinol-4′-O-β-D-glucoside

[38][61]

Vitexin

[36][37][38][59,60,61]

Whole plant

(2S)-2′,4′-dihydroxy-2″-(1-hydroxy-1-methylethyl) dihydrofuro [2,3-h] flavanone

[39][62]

(2S)-abyssinone II

[39][62]

3′-[γ-hydroxymethyl-(E)-γ-methylallyl]-2,4,2′,4′-tetrahydroxychalcone 11′-O-coumarate

[39][62]

5,7,2′,4′-tetrahydroxy-3-geranylflavone

[39][62]

Demethylmoracin I

Isolicoflavonol

Leaf

[39]

[39][62]

3. Application of Paper Mulberry in Cosmetics

3.1. Skin Lightening and Moisturizing

Paper mulberry is commonly used as a skin-lightening agent in cosmetics. Paper mulberry might prevent skin hyperpigmentation by inhibiting the activity of tyrosinase and melanin formation [58][88]. Extracts from paper mulberry are included in many skin-whitening compositions for external application [59][60][89,90]. Paper mulberry combined with Styela clava extract is blended into a facial mask sheet for the whitening purpose [61][91]. A mask pack containing paper mulberry showed moisturizing effects on the skin [62][92]. Paper mulberry combined with white ginseng was incorporated in a cosmetic composition for skin moisturizing and smoothing [63][93].

3.2. Hair Protection and Hair Growth

A previous study showed that the application of formulations containing paper mulberry root extract exerted hair-protective effects by improving the tensile strength, optical absorption, and luster of damaged hair [64][97]. Another study on 11 healthy subjects indicated that using a leaf extract of paper mulberry for 12 weeks showed beneficial effects on hair growth, indicated by increased total hair count as compared with the start date of the trial. The underlying mechanism might be through regulating the WNT-β-catenin and STAT6 pathways to promote the proliferation of dermal papilla cells [65][98]. These data suggest the potential application of paper mulberry in hair-care products in cosmetics.
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