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Biological Activities of Paper Mulberry
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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
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Table of Contents

    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]. 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]

    Leaf

    n/a

    In vitro

    66.67~666.67 μg/mL

    Inhibit mushroom tyrosinase

    [41]

    Leaf

    Broussonetones A-C

    In vitro

    IC50 = 0.317 ~ 0.323 mM

    Inhibit mushroom tyrosinase

    [37]

    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]

    Root

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

    In vitro

    IC50 = 9.29~31.74 μM

    Inhibit mushroom tyrosinase

    [15]

    Anti-inflammatory

    Bark

    n/a

    RAW264.7 cells

    10~200 μg/mL

    Inhibit NO and iNOS production

    [42]

    Bark

    n/a

    RAW264.7 cells

    10~80 μg/mL

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

    [43]

    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]

    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]

    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]

    Root

    Broussochalcone A

    RAW264.7 cells

    1~20 μM

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

    [45]

    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]

    Root

    Broussoflavonol H

    Jurkat cells

    IC50 = 9.95 μM

    Decrease IL-2 production

    [15]

    Root, fruit

    Betulin, betulinic acid

    Rat

    0.6, 1, 2 g/kg

    Reduce edema

    [17]

    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]

    n/a

    Papyriflavonol A

    Rat

    12.5~50 mg/kg

    Inhibit IgE-induced passive cutaneous anaphylaxis

    [47]

    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]

    Leaf

    Luteolin, luteoloside, orientin, isoorientin

    10 μg/mL

    In vitro

    Radical-scavenging activities in DPPH and ABTS assays

    [38]

    Leaf

    Broussonetones A−C, apigenin, vitexin

    IC50 = 43.89~107.7 μM

    In vitro

    Antioxidant effects in SOD-like effect assays

    [37]

    Root

    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]

    Bark, wood

    Epicatechin, caffeic acid, coumaric acid, quercetin, kaempferol

    10~50 mg/mL

    In vitro

    Superoxide anion radical and hydroxyl radical scavenging activities

    [24]

    Flower

    n/a

    0.5~5 mg/mL

    In vitro

    Scavenging activity of DPPH radical

    [4]

    Fruit

    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]

    Branch, twig

    Kazinol M, broussoflavonol A/B

    THP-1 cells

    1 μM

    Reduce CAA values

    [26]

    Root

    Broussochalcone A

    RAW264.7 cells

    1~20 μM

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

    [45]

    Root

    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]

    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]

    Whole plant

    Lignins

    In vitro

    10~100 mg/L

    Scavenging activity of DPPH radical

    [49]

    Aerial part

    n/a

    Beef cattle

    5~15% in food

    Increase SOD concentration, total antioxidant capacity

    [50]

    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]

    Leaf

    n/a

    Piglet

    150, 300 g/t

    Increase concentration of CAT, SOD, glutathione peroxidase

    [52]

    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]

    Seed

    Hexadecanoic acid, heptadecene-8-carbonic acid, caryophyllene

    In vitro

    0.125~1%

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

    [34]

    Aerial part

    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]

    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]

    Root

    Papyriflavonol A

    In vitro

    MIC = 10~25 μg/mL

    Antifungal effect against C. albicans and S. cerevisiae

    [20]

    Fruit

    Polysaccharides

    In vitro

    0.4~2.0 mg/mL

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

    [33]

    Root

    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]

    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]

    Anticancer

    Bark

    n/a

    HT-29 cells

    50~200 μg/mL

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

    [42]

    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]

    Bark, leaf, fruit

    n/a

    MCF-7, HeLa, HepG2 cells

    31.25~1000 μg/mL

    Cytotoxic activity against cancer cells

    [55]

    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]

    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]

    n/a

    Broussochalcone A

    HEK293, HCT116, SW480, SNU475 cells

    5~20 μM

    Induce apoptosis in colon and liver cancer cells

    [56]

    n/a

    Broussochalcone A

    HepG2 cells

    5 µM

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

    [57]

    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]

    Antidiabetic

    Root

    Broussoflavonol B, kazinol J

    Mice

    40 mg/kg

    Improve glucose tolerance

    [44]

    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]

    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]

    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]

    Antigout

    Root

    3,4-dihydroxyisolonchocarpin, broussochalcone A

    In vitro

    IC50 = 0.6~1.8 μM

    Inhibit the activity of xanthine oxidase

    [9]

    Antinociceptive

    Root, fruit

    Betulin, betulinic acid

    Rat

    1, 2 g/kg

    Inhibit writhing responses

    [17]

    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]

    Root

    Broussoflavonol B, kazinol J

    Mice

    40 mg/kg

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

    [44]

    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]. Extracts from paper mulberry are included in many skin-whitening compositions for external application [59][60]. Paper mulberry combined with Styela clava extract is blended into a facial mask sheet for the whitening purpose [61]. A mask pack containing paper mulberry showed moisturizing effects on the skin [62]. Paper mulberry combined with white ginseng was incorporated in a cosmetic composition for skin moisturizing and smoothing [63].

    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]. 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]. These data suggest the potential application of paper mulberry in hair-care products in cosmetics.

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      Nguyen, L.T.H. Biological Activities of Paper Mulberry. Encyclopedia. Available online: https://encyclopedia.pub/entry/35105 (accessed on 01 December 2022).
      Nguyen LTH. Biological Activities of Paper Mulberry. Encyclopedia. Available at: https://encyclopedia.pub/entry/35105. Accessed December 01, 2022.
      Nguyen, Ly Thi Huong. "Biological Activities of Paper Mulberry," Encyclopedia, https://encyclopedia.pub/entry/35105 (accessed December 01, 2022).
      Nguyen, L.T.H. (2022, November 17). Biological Activities of Paper Mulberry. In Encyclopedia. https://encyclopedia.pub/entry/35105
      Nguyen, Ly Thi Huong. ''Biological Activities of Paper Mulberry.'' Encyclopedia. Web. 17 November, 2022.
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