Table 3.

Polyphenols with combined antioxidant capacity and skin senotherapeutic activity: the route of administration, research model used, aging inductor, and proposed mechanisms of action.

Polyphenol	Route of Administration	Aging Inductor	Research Model	Mechanism	Main Senotherapeutic Effects	Reference
Apigenin	In vitro	UVA and UVB	Human dermal fibroblasts	↓ ROS ↓ NF-kB pathway ↓ MAPK ↓ MMP-1	↑ Viability ↑ Collagen synthesis ↑ DNA repair	[148,168]
	Topical	UVA	Mice	↓ ROS ↓ NF-kB pathway ↓ MAPK ↓ MMP-1	↑ Dermal thickness ↑ Collagen deposition	[169]
Baicalin	In vitro	UVB	Human dermal fibroblasts, human skin samples	↓ ROS ↓ MMP-1, MMP-3 ↓ p16, p21, p53	↑ Collagen synthesis ↑ Viability ↓ DNA damage ↓ Apoptosis	[81]
	In vitro	UVC	Human keratinocytes	↓ ROS	↓ DNA damage	[170]
Ferulic acid	In vitro	UVA	Human dermal fibroblasts	↓ ROS ↑ SOD1 ↑ CAT ↓ p16 ↓ MMP-1, -3	↑ Proliferation and cell cycle ↑ ECM reconstruction	[171]
Fisetin	In vitro	Hydrogen peroxide	Human keratinocytes	↓ ROS ↓ NF-kB ↓ iNOS ↓ COX-2 ↓ IL-1β, -6, TNF-α	↓ SASP secretion ↑ Viability	[172]
	In vitro	UVB	Human dermal fibroblasts	↓ ROS ↓ MAPK/AP-1/MMP	↓ SASP secretion ↓ Collagen degradation	[173]
Gallic acid	In vitro	UVB	Human dermal fibroblasts	↓ ROS ↓ MMP-1 ↓ IL-6	↑ Procollagen type I	[174]
	Topical and oral	UVB	Mice	↑ TGF-β1 ↓ MMP-1 ↓ IL-6	↓ Wrinkle formation ↓ Skin dryness ↑ Procollagen type I ↑ Elastin
Genistein	Topical	UVB	Mice	↓ ROS ↓ DNA pyrimidine dimer formation	↓ DNA damage	[175]
Luteolin	In vitro and topical	UVA	Human dermal fibroblasts, human keratinocytes, and human skin explants	↓ ROS ↓ MMP-1 ↓ IL-6, -20 ↓ p38/MAPK	↓ SASP secretion ↓ Collagen degradation ↓ Hyaluronic acid degradation	[176]
Naringenin	Intraperitoneal	UVB	Mice	↓ ROS ↓ MMP-9 ↓ TNF-α, IFN-γ ↓ IL-1β, -4, -5, -6, -12, -13, -17, -22, -23	↓ SASP secretion ↓ Inflammatory infiltrations	[177]
	Topical	UVB	Mice	↓ ROS ↓ IL-1β, -6, -10, TNF-α	↓ SASP secretion	[178]
Nectandrin B	In vitro	Cell passage ≥72	Human diploid fibroblasts	↓ ROS ↑ AMPK ↓ p16, p21, p27, p53 ↓ Cyclin D1 ↓ SA-β-gal ↓ Caveolin-1	↓ Senescence ↓ Apoptosis	[179]
Piceatannol	In vitro	UVB	Human keratinocytes	↓ ROS ↑ GSH ↓ NF-kB ↓ MMP-1	↓ Melanogenesis ↑ Collagen synthesis ↓ Photoaging	[180]
Quercetin	In vitro	Cell passage ≥17	Human dermal fibroblasts	↓ ROS ↑ SOD2, -3 ↑ CAT ↓ p16, p53	↓ Senescence ↑ Mitochondrial membrane potential	[181]

AMPK: AMP-activated protein kinase; AP-1: activator protein 1; CAT: catalase; ECM: extracellular matrix; GPx: glutathione peroxidase; GSH-Px: plasma glutathione peroxidase; HO-1: heme oxygenase 1; IFN-γ: interferon gamma; IL: interleukin; MAPK: mitogen-activated protein kinase; MCP-1: monocyte chemoattractant protein-1; MDA: malondialdehyde, COX-2: cyclooxygenase 2; MMP: matrix metalloproteinase; NF-kB: nuclear factor kappa B; nHDF: normal human dermal fibroblasts; nPC12: neuronally differentiated phenchromocytoma cells; p16: cyclin-dependent kinase inhibitor 2A; p21: cyclin-dependent kinase inhibitor 1; p27: cyclin-dependent kinase inhibitor 1B; p38/MAPK: mitogen-activated protein kinase p38; ROS: reactive oxygen species; SA-β-gal: senescence-associated beta-galactosidase; SASP: senescence-associated secretory phenotype; SOD: superoxide dismutase; TGF-β1: transforming growth factor beta 1; TNF-α: tumor necrosis factor alpha; UVA: ultraviolet A; UVB: ultraviolet B; UVC: ultraviolet C; ↑: increase; ↓: decrease.