Table 3.

Anti-skin aging of Carica papaya.

Part of the Plant	Extract	Type of Experiment	Results	Reference
Unripe papaya juice		In vitro antioxidant enzyme assays	Papaya juice at 1 mg/mL enhanced SOD (49%) and CAT (40.5%) activities.	[45]
		Western blot analysis	Papaya juice at 1 mg/mL restrained NF-κB translocation to nuclei and downregulated Nrf2 levels.
Leaf	Ethanol extract	In vitro DPPH assay	Ethanol extract at 250 μg/mL showed ROS scavenging effect at 60%.	[47]
		In vitro DCFH-DA assay	Ethanol extract at 50 μg/mL showed potent suppressing action towards UVB-induced ROS production (60%).
		In vitro MMPs and inflammatory cytokines production	Ethanol extract at 50 μg/mL of Carica papaya leaves enhances synthesis and prevents degradation of type I collagen via upregulating TGF-β1 and down-regulating MMP-1 (34% at 50 μg/mL), MMP-3, and IL-6 generation. Ethanol extract at 50 μg/mL of Carica papaya leaves reduced mRNA level of MMP-1 (56.8%) and type I procollagen (288.8%).
		Western blotting assay	Ethanol extract at 50 µg/mL showed AP-1 activation via down-regulating c-Fos (89%) and c-Jun (44%) phosphorylation. Ethanol extract at 50 µg/mL attenuated MAPK activation, and p38 phosphorylation (82%), followed by ERK, and JNK phosphorylation.
	FPP	Double-blinded RCT	FPP at a dose of 4.5 g showed anti-skin aging by demonstrating overall higher skin moisturization, elasticity, and surface evenness. FPP at a 4.5 g inhibited MDA production and up modulation of AQP-3, enhanced SOD and NO levels in FPP-treated group. FPP at 4.5 g downregulated pro-aging factors (CyPA and CD147 genes) suggesting to reduce risk of skin carcinogenesis.	[48]

Abbreviation: DPPH, 2,2-diphenyl-1-picryl-hydrazyl-hydrate; DCFH-DA, dichloro-dihydro-fluorescein diacetate; SOD, superoxide dismutase; MMP, matrix metalloproteinase; RCT, randomized controlled trial, MDA, serum malondialdehyde.