Table 2 The main bioactive compounds (examples of the main flavonoids, catechins, water and fat-soluble vitamins, carotenoids and phytocannabinoids) used in skin cells protection
From: Natural protection against oxidative stress in human skin melanocytes
Compound | Chemical class | Chemical structure | Bioactive functional groups | Mechanisms/pathways | Key effects |
|---|---|---|---|---|---|
Quercetin | flavonoid (polyphenol) | 3,3’,4’,5,7-pentahydroxyflavone | hydroxyl groups | chelates Fe²⁺/Cu²⁺; inhibits ROS; activates Keap1/Nrf2/ARE; inhibits NF-κB; promotes apoptosis in melanoma | antioxidant in healthy cells; prooxidant in melanoma; enhances TYR activity and pigmentation; anti-inflammatory; pro-apoptotic in cancer138,140,143,147 |
Isoquercetin | quercetin derivative | quercetin-3-glucoside | hydroxyl, glucose moiety | activates Nrf2; mitigates UVB damage | enhances antioxidative response; protective in pigmentation disorders and melanoma144,145,146. |
Luteolin | flavonoid (polyphenol) | 3’,4’,5,7-tetrahydroxyflavone | hydroxyl groups | metal ion chelation; NF-κB and HIF-1 inhibition; ROS scavenging | reduces oxidative stress; promotes melanocyte survival; pro-apoptotic in melanoma; reduces inflammation138,140,144,148 |
Kaempferol | flavonoid (polyphenol) | 3,4’,5,7-tetrahydroxyflavone | hydroxyl groups | upregulates HO-1 and MITF pathways | protects melanogenic enzymes; promotes pigmentation; antioxidant141 |
Apigenin | flavonoid (polyphenol) | 4′,5,7-trihydroxyflavone | hydroxyl groups | modulates MAPK, PI3K/AKT | |
Hyperoside | flavonoid glycoside | quercetin-3-O-galactoside | hydroxyl groups, glycosidic bond | activates PI3K/AKT | mitochondrial stabilization; anti-apoptotic; improves melanocyte survival142 |
EGCG | catechin (polyphenol) | epigallocatechin-3-gallate | galloyl, hydroxyl groups | absorbs UVA/UVB; inhibits COX-2; modulates MAPK, PI3K/AKT, STAT3, NF-κB; inhibits HDAC | photoprotective; pro-apoptotic in melanoma; anti-inflammatory; restores tumor-suppressor gene expression137,148 |
AcEGCG | EGCG derivative | acetylated form of EGCG | galloyl, acetyl groups | higher stability; antioxidant; anti-inflammatory | improved delivery and stability in vitiligo models150 |
GSPs | proantho-cyanidins | flavan-3-ol polymers | hydroxyl groups | absorb UVA/UVB; reduce COX-2 expression | DNA protection; photoprotection139 |
Cannabidiol (CBD) | phyto-cannabinoid | phenolic diterpenoid | phenol, alkyl chain | CB2 activation; Nrf2 activation; TRPV1 agonist; PPARγ activation; inhibits NF-κB | antioxidant; anti-inflammatory; restores redox balance; promotes ceramide synthesis; anti-metastatic160,163,165,166,167,168 |
Cannabigerol (CBG) | phyto-cannabinoid | phenolic compound | phenol, alkyl chain | similar to CBD; activates Nrf2; modulates TRP channels | reduces oxidative damage; modulates melanogenesis and lipid metabolism160,162,164 |
Vitamin C (Ascorbic acid) | vitamin (water-soluble) | γ-lactone ring with enediol structure | enediol (OH groups) | reduces TYR activity; scavenges ROS; protects membrane; enhances melanin synthesis | protects melanocytes; antioxidant; can promote melanoma under certain conditions171,172,175,176 |
Vitamin B3 (Niacinamide) | vitamin (water-soluble) | pyridine-3-carboxamide | amide group | inhibits PARP-1; restores NAD⁺ levels; reduces DNA damage; inhibits melanosome transfer | antioxidant; anti-inflammatory; protects DNA; brightens skin by inhibiting melanin transfer184,185,186 |
Vitamin E (α-tocopherol) | vitamin (fat-soluble) | chromanol ring + isoprenoid side chain | phenol group | scavenges lipid peroxyl radicals; synergistic with vitamin C; inhibits DNA oxidation | protects against UVA-induced stress; stabilizes carotenoids; prevents DNA strand breaks177,178 |
α-TF | vitamin E derivative | α-tocopherol ferulate | phenol, ester group | inhibits melanin synthesis; prevents 8-OHdG formation | anti-hyperpigmentation; DNA protection177 |
Vitamin A (Retinoids) | vitamin (fat-soluble) | polyene chain + β-ionone ring | conjugated double bonds | modulates RAR/RXR transcription; enhances collagen; promotes epidermal turnover | stimulates melanogenesis at low doses; reduces pigmentation at high doses; antioxidant; regulates keratinocyte–melanocyte interactions180,181 |
β-carotene | carotenoid (carotene) | chain of 40 carbon atom conjugated double bonds and two β-rings | conjugated double bonds, two β-rings | direct radical scavenging; Nrf2/ARE pathway activation; modulation of NF-κB based inflammation | photoprotection and cellular stabilization against UV-induced oxidative stress, working synergistically with vitamins C and E; increase cancer risks in certain populations195 |
Fucoxanthin | carotenoid (xanthophyll) | 3′-acetoxy-5,6-epoxy-3,5′-dihydroxy-6′,7′-didehydro-5,6,7,8,5′,6′-hexahydro-β,β-carotene-8-one | conjugated double bonds, epoxide, hydroxyl and acetyl groups | inhibits COX-2, MC1R and TYR; decreases VEGF, and MMP-13 expression | skin photoaging prevention; apoptosis induction and reducition of cell migration187,192 |
Astaxanthin | carotenoid (xanthophyll) | (3S,3′S,all-trans)-3,3′-dihydroxy-β,β-carotene-4,4′-dione | conjugated double bonds, hydroxyl and keto groups | inhibits COX-2; decreases prostaglandin E2 expression; decreases XO and NOX activity; modulation of NF-κB/MIF/ILs based inflammation | skin photoaging prevention; apoptosis induction and reducition of cell migration187,192 |
