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Table 1 Anti-aging potential of polyphenols

From: The state of the art in anti-aging: plant-based phytochemicals for skin care

Source

Stress Source

Study Type

Results

References

Protocatechuic acid and Ferulic acid: Series of different concentration between 2.08–166.57 µg/mL

--

In vitro: Skin health-related enzyme activity inhibition

Outperformed effect of protocatechuic acid

Protocatechuic acid: Inhibition of tyrosinase (246.42 µg/mL), collagenase (126.16 µg/mL), elastase (57.69 µg/mL), and hyaluronidase (107.57 µg/mL)

Ferulic acid: Inhibition of tyrosinase (253.58 µg/mL), collagenase (52.85 µg/mL), elastase (75.61 µg/mL), and hyaluronidase (396.12 µg/mL)

[44]

Protocatechuic acid: 10, 20, 50, and 100 µg/mL

UVA: 5 J/cm2

In vitro: Human dermal fibroblasts

↑ Type I collagen amount and inhibition of MMP-1 secretion

[45]

Protocatechuic acid: 0.02% in carboxymethyl cellulose gel

--

Ex vivo: Human skin explants

↑ Collagen synthesis

Protocatechuic acid: 0.02% in lotion, 8 weeks

--

In vivo: 22 womans’ crow’s feet treatment

↓ Skin roughness

Punicalagin and Ellagic Acid: 10− 5 to 10− 9 M

--

In vitro: Human dermal fibroblasts (CCD-1064Sk)

↑ Expression of fibronectin and α-actin mAbs

[46]

Chlorogenic acid: 40 mg/kg, 12 weeks

--

In vivo: MRL/lpr mice with lupus erythematosus

↓ Incidence of skin damage, pathological score of acanthosis/ hypertropy, dsDNA expression andIL-17, IL-17 F, IL-6, IFN-γ level

↔ ANA concentration

[47]

Chlorogenic acid: 0.1, 0.3, 1, 3, and 10 µM

UVA: 12 J/cm2

In vitro: Human dermal fibroblasts (CCC-ESF-1)

↑ Type 1 collagen, total collagen secretion, phosphorylated Smad2/3, Rad51

↓ Col3A1, Col5A1, MMP-1, MMP-3 mRNA

↓ Late apoptotic cells, cleaved PARP, ROS level, γ-H2AX expression

[48]

Epigallocatechin gallate: 25 mg/mL

UVB: 1.7 µmol/m2 s

In vivo: BALB/c mice

↑ Pigmentation, elasticity, collagen fibers, melanosomes

↑ Mitochondria injury index

[49]

Gallocatechin gallate: 12.5, 25, and 50 mg/mL

Epigallocatechin-O-Gallate and Withaferin A

--

In vitro: Molecular docking on Skin health-related enzyme inhibition

Significant inhibitory effects on key enzymes involved in skin aging and oxidative stress, especially when combined

[50]

Epigallocatechin Gallate: 25 µg/mL

UVA: 10 J/cm2

In vitro: Human dermal fibroblasts (CCC-ESF-1)

↓ SA-β-Gal positive cells, hTERT gene, relative telomerase activity

↑ SOD, CAT and GSH-Px

↓ MMP-1, MMP-3, MMP-10, MDA and P66

↑ Telomere length, TGF-β1 secretion, and mRNA level of TIMP-1

[51]

Epicatechin gallate, Epigallocatechin gallate, Epicatechin, Catechin and Epigallocatechin: 1, 5, 10, 20, 50 and 100 µM

--

In vitro: Human dermal fibroblasts (WS1)

↑ Instances of mitophagy, LC3B-I to LC3B-II Ratio

↑ Average number of lysosomes that co-localize with mitochondria

[52]

Quercetin: 2, 10, and 20 µM

--

In vitro: Human skin fibroblasts, mouse skin fibroblasts, L929, and HaCat cells

↑ Cell proliferation, scratch closure rate

[53]

Quercetin: 1.5, 3, and 6 mg/mL, 8 days

--

In vivo: C57BL/6 mice with 4 mm wound

↑ Wound healing rate, positive area of collagen fiber

↑ Relative protein expression of FGF, VEGF, α-SMA, Wnt, β-catenin

Quercetin-loaded olive oil: 5 µg/mL

 

In vitro: Tyrosinase inhibition assay

Tyrosinase activity inhibition: 56.24%

[54]

Kaempferol-3-O-robinobioside

--

Molecular docking on Skin health-related enzyme inhibition

Binding through active sites of collagenase, elastase, and tyrosinase

Collagenase (58.24%), elastase (26.29%), and tyrosinase (69.84%) inhibition

[55]

Quercetin-3- O-rhamnoside (Que-3-Rha) and kaempferol-3-O-galactoside

--

Molecular docking on Skin health-related enzyme inhibition

Binding through active sites of collagenase, elastase, and tyrosinase

Que-3-Rhamnoside: Collagenase (60.24%), elastase (50.28%), tyrosinase (46.54%) inhibition.

Kae-3-Gal: Collagenase (59.84%), elastase (55.56%), and tyrosinase (51.14%) inhibition

[56]

Apigenin: 1 and 2.5% in cream

Hydroquinone: 2.5% in cream

In vivo: C57BL/6 mice

↓ Area of white patches

↓ Cholinesterase activity, MDA, CAT activity

↓ IL-6, TNFα, and IFN-γ, and expression of p38 MAPK

[57]

Hesperidin: 50 µM

Particulate matter2.5: 50 µg/mL

In vitro: Human HaCaT Keratinocytes

↓ ROS in mitochondria, mithochondrial depolarization

↓ Cytochrome c release and DNA damage: phospho-H2A.X protein expression

↓ G0/G1, p53, p27, p21, p16, Bim, Bax, MMP-1, MMP-2, MMP-9, SA-βGal

↑ Cyclin D1, cyclin E, Cdk2, and Cdk4

Restoration of anti-apoptotic proteins Mc-1 and Bcl-2

[58]

Hesperidin, Hesperetin: 1-100 µM

Rutinose, and Rhamnose: 0.25–100 mM

--

In vitro: Skin health-related enzyme activity inhibition

Inhibition of collagenase, elastase, and hyaluronidase

Strong inhibition effect of rutinose on all enzymes

Primarily inhibition effect of hesperidin and hesperetin on hyaluronidase

[59]

Hesperidin, Hesperetin: 1 and 10 µM

Rutinose, and Rhamnose: 1 and 10 mM

Low/high glucose: 25 or 50 mM

AGEs

In vitro: Human dermal fibroblasts

↓ MMP-1, MMP-2, IL-6, and IL-8

↑ Collagen I production

Resveratrol: 10, 20, 40, 60, 80, and 100 µM

UVB: 50 mJ/cm2

In vitro: Human HaCaT Keratinocytes

↑ Cell viability, mRNA levels of GSSH and SOD, GPX-4 and HO-1, VEGF-B

↓ ROS level, Caspase3 and Caspase9, MMP-1, MMP-9, IL-6 and TNF-α

[60]

Resveratrol: 2 mg/kg

UVB: 40, 80, and 120 mJ/cm2

In vivo: ICR mice

Prevented roughness, hypertrophy, erythema, and deep wrinkles

Restored collagen fiber structure

↑ Type III collagen immunoreactivity, COX-2, MAPK pathway-related proteins

↓ Caspase3 and Caspase9, MMP-1, MMP-9, IL-6 and TNF-α

↓ m RNA levels of GSSH and SOD, GPX-4 and HO-1, VEGF-B

Resveratrol: 5, 10, 25, 50, 75, 100, and 200 µmol/L

UVA: 4, 8, 12, 16, 20, 24, 28, and 32 J/cm²

In vitro: Human dermal fibroblasts

↑ Cell Viability, Collagen I expression

Cell Morphology: Normal spindle-shaped morphology maintained; reduced cellular debris.

↓ MMP-1, SA-β-gal activity, apoptosis rates, G1-phase arrest

↑ LC3B and Beclin-1 expression and ↓ p62 expression

[23]

Resveratrol: 100 µmol/L

UVA: 0.35 J/cm²

In vivo: BALB/c mice

Improved erythema and reduced wrinkles

↓ Epidermal thickness, inflammatory cell infiltration, MMP-1

↑ Collagen fiber content

↑ LC3B and beclin-1 expression and ↓ p62 expression

↑ p-AMPK/AMPK ratio

Naringenin: 5 and 10 µM

Lipopolysaccharide: 1 µg/mL

In vitro: Human dermal fibroblasts

↓ NF-κB activity, IL-1β, IL-6, IL-8

↓ mRNA expression of COX-2 and iNOS, PGE2 levels, NADPH oxidase

[43]

Naringenin: 150 µM

UVA: 30 mJ/cm²

In vitro: Human HaCaT Keratinocytes

↓ TRPV1 expression, phosphorylated TRPV1, apoptosis, p53, p21, p16, MMP-1, MMP-9

[61]

Cyanidin-3-O-glucoside and cyanidin-3-O-rutinoside: 10, 50, 100 and 200 µM

Blue light: 2,500 to 20,000 lx

In vitro: Human dermal fibroblasts

↓ ROS level, TNF-α, IL-6, and IL-8, cleavage of caspase-3 and PARP, FAK and MAPK phosphorylation

[62]

Cyanidin 3-O-arabinoside: 1 μM

Dihydrotestosterone 100 nM

In vitro: Human follicle dermal papilla cells

↓ SA-β-gal, upregulation of p21 and p16

↓ Mitocondrial ROS levels and calcium accumulation

↑ FGF6 and FGF4, phosphorylation of p38 MAPK

↓ Expression of SA-β-gal, p21, p16

[63]

  1. ↑: Upregulation, ↓: Downregulation, ↔: No obvious change
  2. α-SMA: Alpha smooth muscle actin, AGEs: Advanced glycated end products, ANA: Anti-nuclear antibodies, AMPK: AMP-activated protein kinase, Bcl-2: B-cell lymphoma 2, CAT: Catalase, Cdk2: Cyclin-dependent kinase 2, Cdk4: Cyclin-dependent kinase 4, COX2: Cyclooxygenase-2, dsDNA: Double-stranded DNA, FAK: Focal Adhesion Kinase, FGF: Fibroblast growth factor, GSH-Px: Glutathione peroxidase, GSSH: Glutathione, HaCaT: Human keratinocyte cells, hTERT: Human telomerase reverse transcriptase, IFN: Interfelon, IL: Interleukin, iNOS: Inducible nitric oxide synthase, LC3B: Microtubule-associated protein 1 light chain 3 beta, mAbs: Monoclonal Antibodies, MAPK: Mitogen-activated protein kinase, Mc-1: Myeloid cell leukemia-1, NF-κB: Nuclear factor kappa B, MDA: Malondialdehyde, MMP: Matrix metalloproteinase, mRNA: Messenger RNA, PGE2: Prostaglandin E2, p53: Tumor protein p53, p-AMPK: Phosphorylated AMP-activated protein kinase, PARP: Poly(ADP-ribose) polymerase, ROS: Reactive oxygen species, TIMP-1: Tissue inhibitor of metalloproteinases-1, SA-β-Gal: Senescence-associated beta-galactosidase, SOD: Superoxide dismutase, TGF-β1: Transforming Growth Factor Beta 1, TRPV1: Transient receptor potential vanilloid 1, VEGF: Vascular endothelial growth factor