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.
Biological Activity |
Part |
Compound |
Model |
Dose |
Detailed Effects |
Reference |
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Antityrosinase |
Leaf |
n/a |
In vitro |
IC50 = 17.68 ± 5.3 μg/mL |
Inhibit mushroom tyrosinase |
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(2R)-7,3′,4′-trihydroxy-6-prenylflavanone |
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Leaf | ||||||||
n/a |
In vitro |
3,3′,4′,5,7-pentahydroxyflavone |
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Broussonetones A-C |
In vitro |
3,4-dihydroxyisolonchocarpin |
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[ | ||||||||
] | ||||||||
66.67~666.67 μg/mL |
IC50 = 0.317 ~ 0.323 mM |
Inhibit mushroom tyrosinase |
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Isogemichalcone C | ||||||||
[ | ||||||||
] | ||||||||
[ | ||||||||
] | ||||||||
Inhibit mushroom tyrosinase | [ | |||||||
Leaf |
[ | ][60] |
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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 |
3′-(3-methylbut-2-enyl)-3′,4′,7-trihydroxyflavane |
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Root | ||||||||
Broussoflavonol B/F/H-K, papyriflavonol A, isolicofavonol, glycyrrhiza flavonol |
In vitro |
IC50 = 9.29~31.74 μM |
Inhibit mushroom tyrosinase |
[15 |
4-hydroxyisolonchocarpin |
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7,8-dihydroxy-6-(3-methylbut-2-en-1-yl)-2H-chromen-2-one |
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8-(1,1-dimethylallyl)-5′-(3-methylbut-2-enyl)-3′,4′,5,7-tetrahydroxyflanvonol |
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] | [ | ] |
Brossoflurenone A |
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Brossoflurenone B |
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Betulin |
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Betulinic acid |
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Broussoaurone A |
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Broussochalcone A |
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Broussochalcone B |
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Anti-inflammatory |
Bark |
n/a |
RAW264.7 cells |
10~200 μg/mL |
Inhibit NO and iNOS production |
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Bark |
n/a |
RAW264.7 cells |
10~80 μg/mL |
Inhibit production of NO, iNOS, TNF-α, and IL-1β |
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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 |
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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 |
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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 |
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Root |
Broussochalcone A |
RAW264.7 cells |
1~20 μM |
Inhibit production of NO, iNOS, TNF-α, and IL-1β |
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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 |
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Root |
Broussoflavonol H |
Jurkat cells |
IC50 = 9.95 μM |
Decrease IL-2 production |
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Root, fruit |
Betulin, betulinic acid |
Rat |
0.6, 1, 2 g/kg |
Reduce edema |
,38] |
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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 |
Broussochalcone C |
[ | ||
n/a | ||||||||
Papyriflavonol A |
Rat |
12.5~50 mg/kg |
Inhibit IgE-induced passive cutaneous anaphylaxis |
Broussocoumarin A |
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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 |
Broussoflavan A |
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Luteolin, luteoloside, orientin, isoorientin |
10 μg/mL |
In vitro |
Radical-scavenging activities in DPPH and ABTS assays |
Broussoflavanonol A |
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Leaf | ||||||||
Broussonetones A−C, apigenin, vitexin |
IC50 = 43.89~107.7 μM |
In vitro |
Antioxidant effects in SOD-like effect assays |
Broussoflavonol B |
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Root | 41] |
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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 |
Broussoflavonol C |
[ | |||
Bark, wood | ||||||||
Epicatechin, caffeic acid, coumaric acid, quercetin, kaempferol |
10~50 mg/mL |
In vitro |
Superoxide anion radical and hydroxyl radical scavenging activities |
Broussoflavonol F |
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Flower |
n/a |
0.5~5 mg/mL |
In vitro |
Scavenging activity of DPPH radical |
Broussoflavonol G |
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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 |
Broussoflavonol H |
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Branch, twig |
Kazinol M, broussoflavonol A/B |
THP-1 cells |
1 μM |
Reduce CAA values |
Broussoflavonol I |
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Root |
Broussochalcone A |
RAW264.7 cells |
1~20 μM |
Inhibit production of NO, iNOS, TNF-α, and IL-1β |
Broussoflavonol J |
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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 |
Broussoflavonol K |
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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 |
Broussonin A |
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Whole plant | ||||||||
Lignins |
In vitro |
10~100 mg/L |
Scavenging activity of DPPH radical |
Broussonin B |
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Aerial part | ||||||||
n/a |
Beef cattle |
5~15% in food |
Increase SOD concentration, total antioxidant capacity |
Broussonol D |
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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 |
Broussonol G |
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Leaf | ||||||||
n/a |
Piglet |
150, 300 g/t |
Increase concentration of CAT, SOD, glutathione peroxidase |
Daphnegiravan H |
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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) |
Glycyrrhiza flavonol A |
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Seed | ||||||||
Hexadecanoic acid, heptadecene-8-carbonic acid, caryophyllene |
In vitro |
0.125~1% |
Antibacterial activity against Staphylococcus aureus, Proteus vulgaris, B. cereus, Enterobacter aerogenes |
Isolicoflavonol |
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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) |
Kazinol A |
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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 |
Kazinol B |
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Root | ||||||||
Papyriflavonol A |
In vitro |
MIC = 10~25 μg/mL |
Antifungal effect against C. albicans and S. cerevisiae |
Kazinol E |
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Fruit |
Polysaccharides |
In vitro |
0.4~2.0 mg/mL |
Antibacterial activity against E. coli, P. aeruginosa, B. subtilis, S. aureus |
Kazinol F |
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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 |
Kazinol J |
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Kazinol V |
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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 |
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Anticancer |
Bark |
n/a |
Kazinol W |
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Oleanolic acid |
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HT-29 cells | 50~200 μg/mL |
Induce apoptosis-related DNA fragmentation, increase the expression of p53, caspase 3, Bax, inhibit cell proliferation |
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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 |
Papyriflavonol A |
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Ursolic acid |
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Bark |
3,4,5-trimethoxyphenyl-1-O-β-D-xylopyranosyl-β-D-glucopyranoside |
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4,5-dicaffeoylquinic acid |
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5,7,3′,4′-tetrahydroxy-3-methoxy-8,5′-diprenylflavone |
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5,7,3′,4′-tetrahydroxy-3-methoxy-8-geranylflavone |
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7,4′-dihydroxy-3′-prenylflavan |
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Broussochalcone A |
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Broussochalcone B |
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Broussoflavonol B |
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Bark, leaf, fruit |
n/a |
MCF-7, HeLa, HepG2 cells |
31.25~1000 μg/mL |
Cytotoxic activity against cancer cells |
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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 |
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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 |
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n/a |
Broussochalcone A |
HEK293, HCT116, SW480, SNU475 cells |
5~20 μM |
Induce apoptosis in colon and liver cancer cells |
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n/a |
Broussochalcone A |
HepG2 cells |
5 µM |
Cytotoxic effects against human hepatoma HepG2 cells with activation of apoptosis-related proteins |
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Fruit |
N-norchelerythrine, dihydrosanguinarine, oxyavicine, broussonpapyrine, nitidine, chelerythrine, liriodenine |
BEL-7402, Hela cells |
IC50 = 5.97~47.41 μg/mL |
Inhibit cancer cell growth |
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Antidiabetic |
Root |
Broussoflavonol B, kazinol J |
Mice |
40 mg/kg |
Improve glucose tolerance |
Broussonin A |
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Broussonin B |
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Caffeic acid |
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Cathayanon H |
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Chlorogenic acid |
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cis-form-5-coffee acylchlorogenic acid |
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Coumaric acid |
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Cryptochlorogenic acid |
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Epicatechin |
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Glyasperin A |
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Isoliquiritigenin |
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Isoquercetin |
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Kaempferol |
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Marmesin |
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Papyriflavonol A |
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Quercetin |
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Uralenol |
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Vomifoliol |
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Branch/twig |
(S)-8-methoxymarmesin |
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3,5,7,4′-tetrahydroxy-3′-(2-hydroxy-3-methylbut-3-enyl) flavone |
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5,7,3′,4′-tetrahydroxy-3-methoxy-8,5′-diprenylflavone |
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5,7,3′,4′-tetrahydroxy-3-methoxyflavone |
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5,7,3′,5′-tetrahydroxyflavanone |
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Brossoflurenone C |
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Broussin |
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Broussoflavonol A |
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Broussoflavonol B |
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Broussoflavonol F |
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[ | ] | [ | ] |
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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 |
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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 |
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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 |
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Antigout |
Root |
3,4-dihydroxyisolonchocarpin, broussochalcone A |
In vitro |
IC50 = 0.6~1.8 μM |
Inhibit the activity of xanthine oxidase |
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Antinociceptive |
Root, fruit |
Betulin, betulinic acid |
Rat |
1, 2 g/kg |
Inhibit writhing responses |
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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 |
Fipsotwin |
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Isolicoflavonol |
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Isoliquiritigenin |
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Kazinol B |
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Kazinol N |
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Kazinol M |
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Kazinol Q |
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Luteolin | ||||||||
Root |
Broussoflavonol B, kazinol J |
Mice |
40 mg/kg |
Suppress hepatic steatosis by decreasing lipogenic gene expression and increasing AMPK phosphorylation |
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Marmesin |
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Papyriflavonol A |
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Quercetin |
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[ | ] | [ | ] |
threo-dadahol A |
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threo-dadahol B |
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Uralenol |
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Fruit |
2-(4-hydroxyphenyl) propane-1,3-diol-1-O-β-D-glucopyranoside |
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3,4-dihydroxybenzoic acid |
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3-[2-(4- hydroxyphenyl)-3-hydroxymethyl-2,3-dihydro-1-benzofuran-5-yl]propan-1-ol |
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4-hydroxybenzaldehyde |
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7-hydroxycoumarin |
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8,11-Octadecadienoic acid |
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8-Octadecenoic acid |
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Arbutine |
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Betulin |
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Betulinic acid |
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Broussonpapyrine |
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Chelerythrine |
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Chushizisin A |
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Chushizisin B |
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Chushizisin C |
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Chushizisin D |
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Chushizisin E |
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Chushizisin F |
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Chushizisin G |
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Chushizisin H |
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Chushizisin I |
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cis-coniferin |
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cis-syringin |
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Coniferyl alcohol |
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Curculigoside C |
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Curculigoside I |
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Dihydroconiferyl alcohol |
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Dihydrosanguinarine |
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Epicatechin |
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erythro-1-(4-hydroxy-3-methoxyphenyl)-2-{4-[(E)-3-hydroxy-1-propenyl]-2-methoxyphenoxy}-1,3-propanediol |
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erythro-1-(4-hydroxyphenyl) glycerol |
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Ferulic acid |
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Linolenic acid |
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Liriodenine |
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Nitidine |
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N-Norchelerythrine |
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Oleanolic acid |
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Oleic acid |
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Oxyavicine |
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Palmitic acid |
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p-coumaraldehyde |
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Polysaccharides |
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Protocatechuic acid |
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Stearic acid |
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threo-1-(4-hydroxy-3-methoxyphenyl)-2-{4-[(E)-3-hydroxy-1-propenyl]-2-methoxyphenoxy}-1,3-propanediol |
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threo-1-(4-hydroxyphenyl) glycerol |
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Ursolic acid |
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Seed |
Caryophyllene |
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Heptadecene-8-carbonic acid |
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Hexadecanoic acid |
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Leaf |
(+)-pinoresinol-4′-O-β-D-glucopyranosyl-4″-O-β-D-apiofuranoside |
3,5,4′-trihydroxy-bibenzyl-3-O-β-D-glucoside |
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4-Caffeoylquinic acid |
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4-Feruloylquinic acid |
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5-Caffeoylquinic acid |
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Apigenin |
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Apigenin-6-C-β-D-glucopyranside |
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Apigenin-7-glucoside |
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Apigenin-7-O-glucuronide |
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Apigenin-7-O-β -D-glucoside |
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Broussonetone A |
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Broussonetone B |
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Broussonetone C |
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Broussoside A |
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Broussoside B |
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Broussoside C |
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Broussoside D |
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Broussoside E |
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Chrysoriol-7-O-β-D-glucoside |
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Cosmosiin |
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Coumaric acid |
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Dihydrosyringin |
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Flacourtin |
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Gentisoyl hexoside |
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Isoorientin |
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Isovitexin |
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Liriodendrin |
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Luteolin |
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Luteolin-7-O-glucuronide |
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Luteolin-7-O-β-D-glucopyranoside |
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Luteoloside |
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Orientin |
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Pinoresinol-4′-O-β-D-glucopyranoside |
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Poliothyrsoside |
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Polysaccharides |
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Syringaresinol-4′-O-β-D-glucoside |
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Vitexin |
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Whole plant |
(2S)-2′,4′-dihydroxy-2″-(1-hydroxy-1-methylethyl) dihydrofuro [2,3-h] flavanone |
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(2S)-abyssinone II |
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3′-[γ-hydroxymethyl-(E)-γ-methylallyl]-2,4,2′,4′-tetrahydroxychalcone 11′-O-coumarate |
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5,7,2′,4′-tetrahydroxy-3-geranylflavone |
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Demethylmoracin I |
Isolicoflavonol |
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Leaf |
[39] |