Table 1.

Biological activities of commercial and orange peel’s hesperidin related to skin anti-aging and skin’s barrier improvement.

Hesperidin/ Extract Type	Hesperidin Levels Tested	Testing Model	Main Biological Properties	Formulation	Potential Applications	Molecular Pathways/ Other Relevant Properties	Ref.
Commercial hesperidin	≈35–70% (w/v)	In vitro non-cellular assays	Radical scavenging activity increase in a dose-dependent manner.	Complex of hesperidin with modified silica (1:1, 1:2 or 2:1 (w/w))	Cosmetics/ Cosmeceuticals	Complex’s antioxidant properties were higher than free hesperidin	[23]
Rutaceae fruits extract	1254.67 μg/mL	S. epidermidis E.coli P. acnes	Radical scavenging activity; Antibacterial activity against S. epidermidis, E. coli and P. acnes.	Mixed Rutaceae fruits hesperidin-rich ethanolic extract fermented with mushroom mycelium	Cosmetics/ Cosmeceuticals	N/A	[35]
C. unshiu peel extract	0.25–1% (w/v)	HDFs cells	MMP-1 expression decreases in a dose-dependent manner; Senescent cells decrease; Collagen biosynthesis increases.	C. unshiu peel extract fermented with S.commune	Cosmetics/ Cosmeceuticals	N/A	[44]
Citrus sinensis peel bagasse	Corrosion tests: 100 µg/mL Collagenase assay: 0.08–0.9 mmol/L	FTS cells	Chelation activity; Collagenase inhibition; Antioxidant activity.	Nanoemulsion: hesperidin; glycerol; orange oil, poloxamer (Pluronic F127); and water. Nanoemulsion Silky Cream: BisPEG/PPG-16/16 PEG/PPG-16/16 dimethicone; caprylic/capric triglyceride (1%); muru muru butter (1%); cupuaçu butter (1%); andiroba oil (3%); GMS (2%); cetostearyl alcohol (3%); mineral oil (5%); carbopol ULTREZ 10 (0.2%); nano-emulsion (79.8%); triethanolamine (5 drops); vit E-acetate (0.05%); ethylhexylglicerin, phenoxy-ethanol (0.05%)	Cosmetics/ Cosmeceuticals	Modulation of MMPs activities	[63]
Commercial hesperidin	50 µM	HaCaT cells exposed to PM2.5	Intracellular ROS levels reduction; Apoptotic index reduction; Protein carbonylation and intracellular vacuoles accumulation reversion; Reversion of elevated mitochondrial depolarization; Overall inhibitory effect on PM2.5-induced skin senescence and aging.	N/A	Cosmetics/ Cosmeceuticals	Cell viability restoration via PI3K/Akt activation; MAPK activation and autophagy/apoptosis-related protein expression mitigation; Increase in the anti-apoptotic protein Bcl-2 expression; Cell arrest in the G0/G1 phase decrease; β-galactosidase activity and MMP-associated senescence decrease; Oxidation effects decreased by c-Jun and c-Fos protein levels reduction	[80,81]
Commercial hesperidin	0.02% (w/v)	HaCaT cells	In vitro enhancement of antimicrobial peptide’s mRNA expression.	0.02% hesperidin; 70% ethanol (w/v)	Cosmetics/ Cosmeceuticals	Increase in epidermal differentiation-related protein expression (loricrin and filaggrin); β-glucocerebrosidase and glutathione reductase activity regulation	[84,85]
.	1.03 mmol	In vitro non-cellular assays	Radical scavenging activity.	Hesperidin-conjugated pectins: pectin aqueous solution of 8 g (2.5 wt%); hesperidin intermediate (1.03 mmol) solution into a 7.5 wt% sodium hydroxide solution and epichlorohydrin (1.03 mmol) Hesperidin-conjugated pectins Hydrogels: pectin conjugates (5 wt% pectin solution) individually crosslinked with Ca2+, Zn2+, and Fe3+ (0.22 mM ionic solutions)	Cosmetics/ Cosmeceuticals	Hesperidin’s ion-binding ability induced the crosslinking of the hydrogel conjugates	[86]
Commercial hesperidin	0.05% (w/w)	In vitro non-cellular assays	Formulation’s bioadhesive properties improvement.	Biocomposites of cellulose, collagen, and hesperidin (4:1:0.05 (w/w))	Cosmetics/ Cosmeceuticals	N/A	[87]

HDFs—Human Dermal Fibroblasts; FTS—Full Thickness Skin models; HaCaT—Adult Human Keratinocyte; PM2.5—Particulate Matter with an aerodynamic diameter less than 2.5 µm, studied as an air-pollutant testing model; N/A—Non-Added.