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. 2020 Mar 24;12(3):870. doi: 10.3390/nu12030870

Table 2.

Summary of the key in vivo studies investigating the potential effects of foodborne antioxidants in the skin aging.

References/Country/Study Type Antioxidants/Source Participants/Age Induction Factors Group/Dose/Time Main Result Main Conclusion
Effects of Oral Collagen Peptides on Skin Aging
[133]/China/animal High-, medium- and low-antioxidant peptides (HCP, MCP and LCP)/silver carp skin KM mice/5 week
(25 ± 2 g)
3UV-A + 1UV-B Tg: HCP, MCP, LCP (0,200 mg/kg.bw.d)/0/1/2 weeks 1. ACPs significantly alleviated skin composition and antioxidant index abnormalities induced by UVs.
2. HCP has the best protection effect on skin photoaging, and the difference between MCP and LCP is not obvious.
ACPs have the potential to resist photoaging of the skin.
[134]/China/animal Gelatin (SG)and gelatin hydrolysate (SGH)/
salmon skin
ICR male mice/
20 to 22 g
UV-B Tg: SG (100, 500 mg/kg.bw.d), SGH (100, 500 mg/kg.bw.d); Cg: Vc 100 mg/kg.bw.d/5 week 1. Antioxidant activity of SG and SGH is related to dose, molecular weight and amino acid composition.
2. SG and SGH alleviate oxidative damage by enhancing antioxidant enzyme activity and thymus index
SGH has the potential to be used as an antioxidant in health products and cosmetics.
[135]/Korea/animal Collagen peptide (CP)/
tilapia scale
SKH–1 hairless mice/
6 weeks old
UV-B Tg:CP (0,500, 1000 mg/kg.bw.d) Cg: N–acetyl glucosamine (1000 mg/kg.bw.d)/
9 weeks
1. Oral CP increased skin hydration, reduced wrinkle formation, changed the expression of HAS–1,–2, and maintained the stability of HA.
2. CP regulate the expression of skin moisturizing factor filagglutinin and total chain protein
CP can be used as a nutrient to relieve UV-B-induced skin wrinkles, dehydration and water loss.
[136]/Brazil/cell Collagen Hydrolysate (CH)/cow HDFs Cg:CH (0.5, 1.0, 2.5 and 5.0 mg/mL)/48 h 1. CH regulates cell metabolism without cytotoxicity.
2. CH maintains intracellular protein stability by inhibiting the activity of MMP 1 and 2.
This CH has protective effects on skin cells and has the potential to become a food supplement.
[137]/Korea/clinical Low-molecular-weight Collagen peptide (LMWCP)/
catfish’s skin
Women/40–60 years old Age Tg:LMWCP; 1000 mg/d. Cg: placebo; (0/6/12) weeks Oral LMWCP protects photoaged skin by improving skin wrinkles, hydration and elasticity LMWCP can be used as a functional food ingredient to relieve skin photoaging.
[138]/China/animal Collagen hydrolysates (CHs)/Nile tilapia skin ICRmice/38 ± 4 g, 9-month-old Age Tg:CHs (0%, 2.5%, 5%, 10%); Ng: weaned mice; Cg: (WC, 10%
whey protein hydrolysates)/180 days
1. CHs significantly improves skin visual appearance, tissue structure and matrix homeostasis.
2. CHs alleviates oxidative stress by increasing skin antioxidant activity
CHs can be used as a functional nutritional food against skin aging, but its molecular mechanism is not clear.
[139]/China/animal Elastin peptides (EH)/bovine arteries Female mice/ (20 ± 2 g) UV Nc:vehicle-treated mice; Mg:vehicle-treated + UV. EH group:UV + EH (100 mg/kg.bw.d)/8 weeks EH can significantly reduce UV-induced epidermal hyperplasia and fibroblast apoptosis, and increase skin hydroxyproline and water content EH has the potential to prevent and regulate skin photoaging
[140]/China/animal Collagen peptides (CPs)/silver
carp skin
Mice/(8, 13-month-old (28 ± 2, 45 ± 5 g) Age Cg: young mice (normal saline); Tg: old mice (CPs: 400 mg/kg.bw.d); Mg: Old mice (normal saline)/2 months 1. CPs promotes skin collagen synthesis by regulating cytokines in skin and serum.
2. Intake of CPs inhibited platelet release.
CPs has the potential to be an anti-aging, anti-
cancer and anti-
cardiovascular health product
[141]/Canada/cell Collagen peptides (CPs)/Chicken meat HDFs cells/
human skin
DCF-DA Tg: Two peptides, hydrolyzed by two enzymes (0, 2.5 mg/mL)/24 h Two chicken collagen peptides have significant effects on inflammatory changes, oxidative stress, type I collagen synthesis, and cell proliferation in skin HDFs CPs hydrolyzed by different enzymes have different protective and regulatory effects on skin fibroblasts
[142]/Canada/cell Collagen peptides (CPs)/porcine/
bovine/tilapia/hen skin
HDFs/
human skin
UV-A Tg: Four kinds of collagen peptides (0, 0.5, 1, 2, 4 mg/mL)/24 h 1. Bovine CH inhibits the MMP–1 production.
2. Tilapia CH promotes cell viability and type I collagen generation, while inhibiting ROS and MMP–3 generation.
3. Hen CH promotes collagen production and reduces ROS, MMP–1 and 9 generation and the expression of apoptotic genes.
Hen CH protects HDFs from UV-A-induced damage better than pigs, cattle and tilapia.
[143]/China/animal High, low molecular weight collagen hydrolysates (HMCH/LMCH)/Silver Carp Mice/5weeks (25 ± 2 g) UV-A + UV-B Tg1:UV + LMCH (HMCH)(50, 100, 200 mg/kg.bw.d)/6 weeks; Tg2:UV+LMCH (HMCH) (200 mg/kg.bw.d)/
2 weeks
1. Both HMCH and LMCH increase skin components and antioxidant enzyme activity in skin and serum.
2. LMCH is more effective than HMCH.
3. Skin hydroxyproline, HA, and moisture content depend on peptide dose.
LMCH extracted from silver carp skin can be used as a dietary supplement to prevent skin aging.
[144]/Japan
/clinical
High, low purity collagen hydrolysate (H-CP/L- CP)/fish gelatin Female/(35–55 years old) Age H-CP group: 5 g/d; L-CP group: 5 g/d; Cp: placebo; 0/4/8 weeks. H-CP is more significant than L-CP in improving facial skin moisture, elasticity, wrinkles, and roughness. L-CP and H-CP are both effective dietary supplements to improve skin conditions.
[145]
/Thailand
/cell/animal
Collagen hydrolysate (HC)/Lates calcarifer skin HDFs/human; Wistar rats (214 ± 26 g) Mice Tg: (0,2000,5000 mg/kg.bw.d)/15d;
Cell Tg: (50, 100, 150 and 200 µg/mL)/24 h.
1. Animal and cell experiments prove that HC is non-toxic.
2. HC can promote the growth of fibroblasts and the synthesis of cellular collagen, but not as effective as HC combined with VC.
Single HC or HC combined with VC can be used as nutritional health products for skin care.
[146]/China
/cell
Gelatin hydrolysates (CGH)/Cod skin HDF cells/
Mouse skin
UV-B Tg: CGH (0, 0.001, 0.01, 0.1,1, 10) mg/mL
/24 h.
1. CGH inhibits the expression of MMP–1 in fibroblasts induced by UV-B.
2. Purified MMP–1 inhibitory peptides have significant inhibitory effects on MMP–1, p-ER and p-p38.
CGH can be used as a functional supplement for skin care.
[147]/China
/cell/animal
High, medium, low antioxidant peptide (HCP/
MCP/LCP)/Silver carp skin; Serum collagen
peptides (SCP)/
rat serum
SD rat (8 week); ESF cells/skin UV-A Rats Tg (HCP, MCP and LCP)/(2.4 g/kg.bw.d)/2 h; Cell Tg: (SHCP, SMCP and SLCP)/(0, 50, 200 µM/mL)/24 h. 1. SCP is the active component of serum metabolites, which shows repair effect by removing ROS.
2. SCP promotes collagen synthesis and inhibits its degradation by activating TGF-β/Smad3 pathway and inhibiting the expression of AP–1 and MMP–1,3,SHCP is the best one.
CP promotes photoaging skin repair by activating the TGF- TGF/Smad pathway and inhibiting collagen reduction.
[148]/China
/animal
Alcalase,
Collagenase Collagen peptide (ACP/CCP)/
bovine bone
Mice/(8, 13-month-old (28 ± 2, 45 ± 5 g) Age Cg: young mice (normal saline); Tg: old mice/ACP (200, 400, and 800 mg/kg.bw.d), CCP (400 mg/kg.bw.d)/8 weeks Oral CPs improve skin relaxation, increase collagen content and antioxidant enzyme activity, repair collagen fibers, and normalize the ratio of skin collagen. ACP is better than CCP. CP can alleviate the chronological aging of the skin and has the potential to become an anti-aging functional food.
[149]/Korea
/animal/cell
Collagen peptide NS (CPNS)/fish scale HDF cells
/human,
Mice/8 weeks old (25–30 g)
UV-B Cell Tg: CPNS (0, 50, 100, 250, 500 µg/mL)/24 h; Mice Tg: CPNS (300, 500 mg/kg.bw.d)/12weeks 1. CPNS treatment reduced the production of MMP–1 and increased the synthesis of type 1 procollagen in HFD cells.
2. Oral CPNS significantly reduced skin wrinkle formation, epidermal water loss, epidermal thickness, and increased hydration.
CPNS are a potential food supplement to prevent skin aging.
[150]/China
/animal
Gelatin/Amur sturgeon swim bladder Female
SD rat/6 months old
Age Cg (8% whey protein); Tg (8%, 4%, 2%)/12 months. 1. Oral administration of 3.85 g/kg.bw.d gelatin significantly improved skin histological structure and collagen ratio.
2. Skin antioxidant activity increased.
The gelatin improves the foundation for the development of anti-aging foods.
[110]/China
/animal
Protein hydrolysate (WPH)/Walnut SD rats/
180–200 g
UV-A + UV-B Cg:( distilled water); Tg: UV-R + WPH (0, 0.32, 0.98, 2.88 g/L)/18 weeks 1. WPH significantly enhances skin elasticity and promotes the biosynthesis of Col I, Hyp, and HA.
2. WPH inhibits MMP–1 activity and repairs skin damage.
3. WPH repair effect becomes dose dependent, high dose is best.
WPH has potential as a functional food ingredient against photoaging.
Effects of Oral Polyphenol on Skin Aging
[151,152]
/China/cell
/animal
Polyphenol extract (HPE)/hawthorn HDFs and HaCaT/human; mice/5–6 weeks old UV-B Cell Tg: HPE (0, 5, 10 µg/mL)/24 h; Mice
Tg: HPE (0, 100, 300 mg/kg.bw.day)/12 weeks
1. HPE treatment can promote cell proliferation, increase intracellular collagen and reduce MMP–1 production.
2. Oral HPE reduces UV-B-induced skin damage by eliminating ROS, reducing DNA damage and inhibiting p53 expression.
HPE can be used as an anti-aging food or cosmetic ingredient.
[153]/Spain
/clinical
Products rich in polyphenol (NutroxsunTM)/rosemary and citrus Adult female UV-B + UV-A Long-term: NutroxsunTM (250 mg/day)/
2 weeks; Short-term: NutroxsunTM (100, 250 mg/day)/24, 48 h
1. Dietary NutroxsunTM reduces UV- induced skin changes, wrinkles and elasticity improvements.
2. The improvement effect between two doses is not obvious.
Long-term oral NutroxsunTM can be used as a nutritional supplement to improve skin conditions.
[154]/Korea
/cell
Polyphenolic-
rich extract (SSE and SSW)/Spatholobus Suberectus stem
HaCaT/Human skin UV-B Tg1: SSE (0, 3, 10, 30, 300 µg/mL); Tg2: SSW (0, 3, 10, 30, 300 µg/mL)/24 h 1. SSE and SSW inhibited ROS production and cell damage.
2. SSE repairs skin by upregulating the expression of enzymes and proteins in cells, blocking UV-B-induced MAPKs phosphorylation and its downstream transcription factor.
SSE can be used as a natural biomaterial to inhibit UV-B-induced photoaging.
[155]/China
/animal
Rambutan peel phenolics (RPP)/Nephelium lappaceum; Leu-Ser-Gly-Tyr-Gly-Pro
(LSGYGP)/synthetic
Male BALB/c nude mice/20–22 g UV-B Single group: RPP (100 mg/kg.bw. d), SGYGP (100 mg/kg.bw.d); Composite group: (50 RPP+ 50 LSGYGP) mg/kg.bw.d, (100 RPP + 100 LSGYGP)mg/kg.bw.d/10 weeks 1. RPP and LSGYGP improve skin biochemical indicators, tissue structure and collagen levels.
2. RPP enhances the regulation of oxidative stress and inflammatory factor levels.
3. LSGYGP significantly affects skin collagen and HA content.
Oral RPP and LSGYGP can alleviate UV-B- induced skin aging.
[156]/Korea
/animal
Polyphenols/Flavonoid hesperidin exerts Male hairless mice/6-
week-old
UV-B Cg: water; Tg: UV-B + hesperidin (0, 100 mg/kg.bw.d)/12 weeks 1. Oral hesperidin inhibited UV-B-induced skin thickening and wrinkle formation.
2. Hesperidin inhibited UV-B-induced expression of MMP–9 and cytokines, and protected collagen fiber loss.
Oral hesperidin regulates MMP–9 expression by inhibiting MAPK-
dependent signaling pathways to relieve skin photo-aging.
[157]/Korea
/cell
Polyphenols/3,5,6,7,8,3,4-heptam-ethoxy flavone (HMF)/C. unshiu peels HDFn cells/human dermal UV-B HMF (0, 50, 100, 200 µg/mL)/24 h 1. HMF protects UV-induced HDFn cell damage by inhibiting MMP–1 expression through phosphorylated MAPK signals.
2. HMF regulates the expression of Smad3 and Smad7 proteins in a dose-dependent manner.
HMF has the potential to be an anti-aging cosmetic or food supplement.
[158]/Korea
/cell
Polyphenols/
Tectorigenin/
Belamcanda chinensis L
HaCaT cells/human UV-B Tg: Tectorigenin (0,
0.1, 1,10 µM); Cg: VC (200 µM)/24 h
1. Tectorigenin lowers ROS levels by increasing intracellular antioxidant enzymes.
2. Tectorigenin reduces mmp–1 and inhibits collagen degradation.
3. Tectorigenin inhibits apoptosis by regulating the levels of caspase–3 and bcl–2 related proteins.
Tectorigenin alleviates skin damage by inhibiting UV-B-induced cellular oxidation, apoptosis and collagen degradation.
Effects of Oral Polysaccharides on Skin Aging
[116]/China
/animal
Polysaccharides
(TP)/T. fuciformis
SD rats/6~7 weeks old (180–220 g) UV-A + UV-B Cg: no irradiation;
Tg group: UV + TP (0, 100, 200, 300 mg/kg.bw.d)/12 weeks
Oral TP can alleviate UV-induced skin structural changes, repair collagen damage, maintain the I/III collagen ratio and enhance skin antioxidant enzyme activity. TP has the potential to become a skin-protective functional food additive.
[117]/Korea
/cell
Polysaccharide (HFPS)/Hizikia fusiforme HDF cells UV-B Cg: no irradiation;
Tp: UV + HFPS (0, 25, 50, 100 µg/mL)/24 h
1. HFPS significantly reduces cell ROS and increases the pure activity rate. 2.HFPS inhibits UV-induced skin damage by regulating NF-κB, ap–1 and MAPKs signaling pathways. HFPS has a strong anti-ultraviolet effect and is a potential pharmaceutical, food, and cosmetic ingredient.
[118]/China
/cell
Polysaccharide
(LBP)/Lycium barbarum
HaCaT cells UV-B Tg1: LBP (0, 50, 100, 300, 600, 1500, 3000 µg/mL)
24 h; Tp2: UV-B + LBP (0, 300 µg/mL)/24 h
LBP mainly eliminates ROS and reduces DNA damage. In part, the Nrf2/ARE pathway is activated to inhibit the p38 MAP pathway, thereby inhibiting the activation of caspase–3 and the expression of mmp–9 to protect the aging cells. LBP may be used as a protective agent or food additive against skin oxidative damage.
[119]/China
/cell
Polysaccharide
(GL-PS)/Ganoderma lucidum
Fibroblast/men foreskin UV-B Tg: UV-B + GL-PS (0, 10, 20, 40 µg/mL) 24 h; Tg: no UV-B and GL-PS/24 h After GL-PS treatment, cell activity increased, senescent cells decreased, CICP protein expression increased, MMP–1 protein expression decreased, and cell ROS level decreased. GL-PS protects UV-B- induced cell photoaging by eliminating intracellular ROS, which will provide strategies for subsequent studies.
[120]/China
/animal
Polysaccharide (SFP)/Sargassum fusiforme Female KM mice/7 weeks old (20–25 g) UV-B Cg: UV-B + sodium hyaluronate (400 mg/kg. bw/d); SFP Tg: UV-B + SFP (0, 200, 400, 600 mg/kg.bw/d)/9 weeks 1. SFP regulates mouse chest, spleen index and skin water content.
2. SFP increases skin antioxidant enzyme activity, reduces ROS, and reduces oxidative damage.3.SFP inhibits MMP–1 and 9 levels in the skin.
SFP can be a potential functional food additive for skin protection.
[121]/China
/cell/animal
Purified, crude polysaccharide (TLH–3,TLH)/
Tricholoma lobayense
HELF cells/human; Mice/8 weeks
(23 ± 2 g)
t-BHP/D-galactose Cell Tg: TLH–3 (0, 50, 100, 200, 400 µg/mL), Pc: Vc (50 ug/mL)/24 h; Mice Tg: TLH–3 and TLH (200 mg/kg. bw/d),Pc: Vc (100 mg/kg. bw/d)/5 weeks 1. TLH–3 relieves cell senescence by regulating the expression of bcl–2, bax, caspase–3 proteins, inhibiting senescence-related enzyme levels.
2. TLH–3 reduced skin pathological lesions by reducing IL–6, LPF, AGEs, and enhanced MAO activity.
TLH–3 is an active polysaccharide that protects cells and mice from oxidative stress aging.
Effects of Oral Vitamins on Skin Aging
[159]/China
/cell
Vitamin Coenzyme Q10 (CoQ10) ESF and HaCaT cells/
Human
UV-A, UV-B Cg: ESF, HaCat (CoQ10 (0, 0.5, 1, 2 µM))/24 h; Tg: ESF, HaCat (UV-A or UV-B + CoQ10 (0, 1, 5, 10 µM))/24 h 1. CoQ10 treatment promoted ESF cell proliferation, type IV collagen and elastin gene expression.
2. CoQ10 treatment inhibited UV-induced IL–1a production in HaCaT cells.
CoQ10 has anti-aging effect on chronological aging and photo-aging and can be used in food and cosmetics.
[122]/Japan
/clinical
VC, VE, and Astaxanthin (AX) Female/(mean age 37.26 years) - Tg1:AX (6 mg) + VC (1000 mg) + VE (10 mg)/d; Tg2:VC (1000 mg) + VE (10 mg)/d/20 weeks Tg 1 significantly improved skin moisture content, skin elasticity and wrinkles; Tg 2 did not improve the
skin significantly.
Oral formulations containing astaxanthin and vitamin C and E have skin-improving effects.
[160]/Iran
/animal
Silymarin,
Vitamin C
Balb/C mice/6 weeks old (30 ± 2 g) UV-B Cg: Silymarin (100),VC
(40 mg/kg.bw/d)/; Tg: UV-B + Silymarin (0, 100 mg/kg.bw/d), UV-B + VC: (0, 40 mg/kg.bw/d)/4 weeks.
Oral VC enhances skin antioxidant enzyme activity, reduces skin wrinkle formation and thickness increase in mice induced by UV-B. Salicylic acid and vitamin C can be used as food or cosmetic ingredients to resist skin photo-aging.
[161]/Korea
/cell
Niacinamide (NIA) HaCaT/
human
PM2.5 Cg: NIA (0, 12.5, 25, 50, 100, or 200 µM); Tg: NIA (0, 12.5, 25, 50, 100, or 200 µM) + PM2.5 (50 µM)/24 h NIA treatment can inhibit the oxidation of lipid, protein, DNA and other molecules induced by PM 2.5, as well as inhibit apoptosis and ROS production. NIA protects cells from PM 2.5-induced oxidative stress and cell damage.
Effects of Oral Fatty Acids on Skin Aging
[125]/Brazil
/animal
0live oil Swiss mice/8–12 weeks age Rotational stress Stress group: stress + olive (1.5 g/kg.bw. d), Cg: olive (1.5 g/kg. bw/d)/29 d Olive inhibited skin ROS, lipid peroxidation, protein carbonylation, phenolamine synthesis, MMP–8 expression and promotes collagen deposition in mice through NF-κB and NRF2 pathways. Oral administration of olive oil can reduce mice skin aging induced by stress.
[126]/Korea
/animal
7-MEGATM500/> 50% of palmitoleic acid containing fish oil, omega–7 H–1 mice/5-week old (18–20 g) UV-B Cg: 30% EtOH; Tp: 7-MEGATM500 (50, 100, 200 mg/kg.bw/d)/4 weeks 1.7-MEGATM 500 improves skin histological indicators and significantly down-regulated the expression levels of MMP–3 and c-jun genes and proteins in the skin. 7-MEGATM500 can alleviate UV-B induced skin photoaging in mice
[129]/Korea
/cell
Fermented
Fish Oil (FFO)
HaCaT/
human
PM2.5 Cg: PM2.5;
Tp:PM2.5 + FFO (0,
20 µg/mL)/24 h
FFO can inhibit PM 2.5-induced intracellular ROS, Ca 2+ levels and MMPs–1,2,9 production, and block the MAPK/AP–1 pathway. FFO can alleviate PM 2.5 induced skin aging.
[162]/Japan
/animal
Coconut oil Female mice/(6 weeks old) DNFB Cg: Coconut or soybean oil (4%)/2 months; Tg: Coconut or soybean oil (4%)/after 2 months + DNFB Oral coconut oil improves BDFB-induced skin inflammation in mice. Mechanistically related to elevated mead acid in serum inhibiting directional migration of neutrophils. Dietary coconut oil improved skin contact allergies in mice by producing midic acid.

Cg = control group; Tg = test group; Ng = normal group; Mg = model group; mg/kg.bw.d = mg/kg. body weight/day; DNFB = 1-fluoro-2,4-dinitro-benzene; HaCaT = Human skin epidermal keratinocytes; t-BHP = tert-butyl hydroperoxide; DCF-DA = dichlorofluorescein diacetate; HAS-1,-2 = hyaluronic acid synthases1and 2; MAO = monoamine oxidase; Co Q10 = Coenzyme Q10; LPF = lipofuscin pigment; NF-κB = nuclear factor kappa B; IL-6 = Interleukin-6; IL-1 = Interleukin-1; NRF2 = nuclear factor erythroid-2p45-related factor2; ARE = antioxidant response element; p38 MAP = p38 mitogen-activated protein; MAPKs = Mitogen-activated protein kinases; TGF-β/Smad3 = Transforming growth factor-β/Recombinant Human Mothers Against Decapentaplegic Homolog 3; p-ERK = phosphorylated extracellular regulated kinase; p-p38 = phospho-p38.