Abstract
Chronic exposure to ultraviolet radiation (UVR) leads to premature aging of the skin, with external manifestations of unsightly scars and internal molecular dysregulations that significantly reduce the protective function of the skin and increase the risk of cancer development. Photoprotection through daily application of sunscreen product is widely recommended to avoid UV-induced skin photodamage and to minimaze the risk for dermal malignancies. However, the environmental hazard that is a consequence of the use of traditional sunscreen products drives the increased interest in the investigation of alternative UVR blockers. Due to their structural diversity, modulation of multiple molecular mechanisms, and favorable safety profile, natural plant-derived compounds have become attractive candidates for skin photoaging prevention. This review summarizes the critical aspects of skin photoaging, from its pathological characteristics and current photoprotective options to the specific molecular players that emerge as therapeutic targets. Special emphasis has been placed on phytochemicals targeting the molecular hallmarks of UV-induced skin aging. The potential of plant molecules to control oxidative stress, inflammation, photo-senescence, DNA damage, extracellular matrix components degradation, and to manage different types of UV-trigerred cell death has been highlighted. Summarizing the molecular signalling pathways responsible for the photoprotective action of plant-derived molecules may provide meaningful outlook for development of new effective therapeutics options for prevention of skin photoaging.
![](http://media.springernature.com/m312/springer-static/image/art%3A10.1007%2Fs11101-024-09952-w/MediaObjects/11101_2024_9952_Fig1_HTML.png)
![](http://media.springernature.com/m312/springer-static/image/art%3A10.1007%2Fs11101-024-09952-w/MediaObjects/11101_2024_9952_Fig2_HTML.png)
![](http://media.springernature.com/m312/springer-static/image/art%3A10.1007%2Fs11101-024-09952-w/MediaObjects/11101_2024_9952_Fig3_HTML.png)
![](http://media.springernature.com/m312/springer-static/image/art%3A10.1007%2Fs11101-024-09952-w/MediaObjects/11101_2024_9952_Fig4_HTML.png)
Similar content being viewed by others
References
Ahn H, Kim H, Na C et al (2021) The protective effect of Adenocaulon himalaicum Edgew. and its bioactive compound neochlorogenic acid against UVB-induced skin damage in human dermal fibroblasts and epidermal keratinocytes. Plants 10:1669. https://doi.org/10.3390/plants10081669
Alafiatayoa AA, Laib K-S, Ahmada S et al (2020) RNA-Seq analysis revealed genes associated with UV-induced cell necrosis through MAPK/TNF-α pathways in human dermal fibroblast cells as an inducer of premature photoaging. Genomics 112:484–493. https://doi.org/10.1016/j.ygeno.2019.03.011/j.ygeno.2019.03.011
Atanasov AG, Zotchev SB, Dirsch VM et al (2021) Natural products in drug discovery: advances and opportunities. Nat Rev Drug Discov 20:200–216. https://doi.org/10.1038/s41573-020-00114-z
Avola R, Graziano ACE, Pannuzzo G et al (2019) Hydroxytyrosol from olive fruits prevents blue-light-induced damage in human keratinocytes and fibroblasts. J Cell Physiol 234:9065–9076. https://doi.org/10.1002/jcp.27584
Baek J, Park S, Park J et al (2017) Protective role of mitochondrial peroxiredoxin III against UVB-induced apoptosis of epidermal keratinocytes. J Invest Dermatol 137:1333–1342. https://doi.org/10.1016/j.jid.2017.01.027
Barresi C, Rossiter H, Buchberger M et al (2022) Inactivation of autophagy in keratinocytes reduces tumor growth in mouse models of epithelial skin cancer. Cells 11:3691. https://doi.org/10.3390/cells11223691
Bustamante M, Hernandez-Ferre C, Tewari A et al (2020) Dose and time effects of solar-simulated ultraviolet radiation on the in vivo human skin transcriptome. Br J Dermatol 182:1458–1468. https://doi.org/10.1111/bjd.18527
Carpenter E, Le M, Miranda C et al (2018) Photoprotective properties of isothiocyanate and nitrile glucosinolate derivatives from meadowfoam (Limnanthes alba) against UVB irradiation in human skin equivalent. Front Pharmacol 9:477. https://doi.org/10.3389/fphar.2018.00477
Chaiprasongsuk A, Panich U (2022) Role of phytochemicals in skin photoprotection via regulation of NRF2. Front Pharmacol 13:823881. https://doi.org/10.3389/fphar.2022.823881
Charachit N, Sukhamwang A, Dejkriengkraikul P et al (2022) (2022) Hyperoside and quercitrin in Houttuynia cordata extract attenuate UVB-induced human keratinocyte cell damage and oxidative stress via modulation of MAPKs and Akt signaling pathway. Antioxidants 11:221. https://doi.org/10.3390/antiox11020221
Chen X, Li L, Xu S et al (2018) Ultraviolet B radiation down-regulates ULK1 and ATG7 expression and impairs the autophagy response in human keratinocytes. J Photochem Photobiol B-Biol 178:152–164. https://doi.org/10.1016/j.jphotobiol.2017.08.043
Chen Q, Zhang H, Yang Y et al (2022a) Metformin attenuates UVA-induced skin photoaging by suppressing mitophagy and the PI3K/AKT/mTOR pathway. Int J Mol Sci 23:6960. https://doi.org/10.3390/ijms23136960
Chen Y, Lian N, Chen S et al (2022b) GSDME deficiency leads to the aggravation of UVB-induced skin inflammation through enhancing recruitment and activation of neutrophils. Cell Death Dis 13:841. https://doi.org/10.1038/s41419-022-05276-9
Chen Y, Liu X, Lei X et al (2022c) Premna microphylla Turcz pectin protected UVB-induced skin aging in BALB/c-nu mice via NRF2 pathway. Int J Biol Macromol 215:12–22. https://doi.org/10.1016/j.ijbiomac.2022.06.076
Childs BG, Durik M, Baker DJ et al (2015) Cellular senescence in aging and age-related disease: from mechanisms to therapy. Nat Med 21:1424–1435. https://doi.org/10.1038/nm.4000
Choi Y-P, Kim G, Kim SH (2020) Suppression of Pax3–MITF-M axis protects from UVB-induced skin pigmentation by tetrahydroquinoline carboxamide. Int J Mol Sci 21:9631. https://doi.org/10.3390/ijms21249631
Choi J-K, Kwon O-W, Lee S-H (2023) Kaempferide prevents photoaging of ultraviolet-B irradiated NIH-3T3 cells and mouse skin via regulating the ROS-mediated signalling. Antioxidants 12:11. https://doi.org/10.3390/antiox12010011
Correia-Melo C, Marques FDM, Anderson R (2016) Mitochondria are required for pro-ageing features of the senescent phenotype. Embo J 35:724–742. https://doi.org/10.15252/embj.201592862
Cui B, Wang Y, ** J et al (2022) Resveratrol treats UVB-induced photoaging by anti-MMP expression, through anti-inflammatory, antioxidant, and antiapoptotic properties, and treats photoaging by upregulating VEGF-B expression. Oxidative Med Cell Longev 2022:6037303. https://doi.org/10.1155/2022/6037303
Dańczak-Pazdrowska A, Gornowicz-Porowska J, Polańska A et al (2023) Cellular senescence in skin-related research: targeted signaling pathways and naturally occurring therapeutic agents. Aging Cell 22:e13845. https://doi.org/10.1111/acel.13845
Dare R, Oliveira M, Truiti M et al (2020) Abilities of protocatechuic acid and its alkyl esters, ethyl and heptyl protocatechuates, to counteract UVB-induced oxidative injuries and photoaging in fibroblasts L929 cell line. J Photochem Photobiol B-Biol 203:111771. https://doi.org/10.1016/j.jphotobiol.2019.111771
Dare R, Kolanthai E, Neal C et al (2023) Cerium oxide nanoparticles conjugated with tannic acid prevent UVB-induced oxidative stress in fibroblasts evidence of a promising anti-photodamage agent. Antioxidants 12:190. https://doi.org/10.3390/antiox12010190
de Assis L, Tonolli P, Moraes M et al (2021) How does the skin sense sun light? An integrative view of lightsensing molecules. J Photochem Photobiol C-Photochem Rev 47:100403. https://doi.org/10.1016/j.jphotochemrev.2021.100403
de Pedro I, Alonso-Lecue P, Sanz-Gómez N et al (2018) Sublethal UV irradiation induces squamous differentiation via a p53-independent. DNA Damage-Mitosis Checkpoint Cell Death Dis 9:1094. https://doi.org/10.1038/s41419-018-1130-8
de Pedro I, Galán-Vidal J, Freije A et al (2021) p21CIP1 controls the squamous differentiation response to replication stress. Oncogene 40:152–162. https://doi.org/10.1038/s41388-020-01520-8
Dhaliwal S, Rybak I, Ellis S et al (2019) Prospective, randomized, double-blind assessment of topical bakuchiol and retinol for facial photoageing. Br J Dermatol 180:289–296. https://doi.org/10.1111/bjd.16918
Ding Y, Jiratchayamaethasakul C, Lee S-H (2020) Protocatechuic aldehyde attenuates UVA-induced photoaging in human dermal fibroblast cells by suppressing MAPKs/AP-1 and NF-κB signaling pathways. Int J Mol Sci 21:4619. https://doi.org/10.3390/ijms21134619
Domaszewska-Szostek A, Puzianowska-Kuznicka A, Kuryłowicz A (2021) Flavonoids in skin senescence prevention and treatment. Int J Mol Sci 22:6814. https://doi.org/10.3390/ijms22136814
Duan X, Wu T, Liu T et al (2019) Vicenin-2 ameliorates oxidative damage and photoaging via modulation of MAPKs and MMPs signaling in UVB radiation exposed human skin cells. J Photochem Photobiol B-Biol 190:76–85. https://doi.org/10.1016/j.jphotobiol.2018.11.018
Feng Z, Qin Y, Huo F et al (2022) NMN recruits GSH to enhance GPX4-mediated ferroptosis defense in UV irradiation induced skin injury. Biochim Biophys Acta-Mol Basis Dis 1868:166287. https://doi.org/10.1016/j.bbadis.2021.166287
Fenini G, Grossi S, Gehrke S et al (2018) Genome editing of human primary keratinocytes by CRISPR/Cas9 reveals an essential role of the NLRP1 inflammasome in UVB sensing. J Invest Dermatol 138:2644–2652. https://doi.org/10.1016/j.jid.2018.07.016
Fernando I, Heo S-J, Dias M et al (2021) (–)-Loliolide isolated from Sargassum horneri abate UVB-induced oxidative damage in human dermal fibroblasts and subside ECM degradation. Mar Drugs 19:435. https://doi.org/10.3390/md19080435
Ferreira SM, Gomes SM, Santos L et al (2023) A novel approach in skin care: by-product extracts as natural UV filters and an alternative to synthetic ones. Molecules 28:2037. https://doi.org/10.3390/molecules28052037
Fitsiou E, Pulido T, Campisi J et al (2021) Cellular senescence and the senescence-associated secretory phenotype as drivers of skin photoaging. J Invest Dermatol 141:1119–1126. https://doi.org/10.1016/j.jid.2020.09.031
Franco A, Aveleira C, Cavadas C (2021) Skin senescence: mechanisms and impact on whole-body aging. Trends Mol Med 28:2. https://doi.org/10.1016/j.molmed.2021.12.003
Galluzzi L, Kepp O, Hett E et al (2023) Immunogenic cell death in cancer: concept and therapeutic implications. J Transl Med 21:162. https://doi.org/10.1186/s12967-023-04017-6
Gao S, Guo K, Chen Y et al (2021) Keratinocyte growth factor 2 ameliorates UVB-induced skin damage via activating the AhR/Nrf2 signaling pathway. Front Pharmacol 12:655281. https://doi.org/10.3389/fphar.2021.655281
Garg C, Sharma H, Garg M (2020) Skin photo-protection with phytochemicals against photo-oxidative stress, photo-carcinogenesis, signal transduction pathways and extracellular matrix remodelling—an overview. Ageing Res Rev 62:101127. https://doi.org/10.1016/j.arr.2020.101127
Gęgotek A, Bielawska K, Biernacki M et al (2017) Time-dependent effect of rutin on skin fibroblasts membrane disruption following UV radiation. Redox Biol 12:733–744. https://doi.org/10.1016/j.redox.2017.04.014
Gu Y, Xue F, **ao H, Chen L, Zhang Y (2022) Bamboo leaf flavonoids suppress oxidative stress-induced senescence of HaCaT cells and UVB-induced photoaging of mice through p38 MAPK and autophagy signalling. Nutrients 14:793. https://doi.org/10.3390/nu14040793
Guo K, Liu R, **g R et al (2022) Cryptotanshinone protects skin cells from ultraviolet radiation-induced photoaging via its antioxidant effect and by reducing mitochondrial dysfunction and inhibiting apoptosis. Front Pharmacol 13:1036013. https://doi.org/10.3389/fphar.2022.1036013
Hao D, Wen X, Liu L et al (2019) Sanshool improves UVB-induced skin photodamage by targeting JAK2/STAT3-dependent autophagy. Cell Death Dis 10:19. https://doi.org/10.1038/s41419-018-1261-y
Hegedűs C, Boros G, Fidrus E et al (2020) PARP1 inhibition mugments UVB-mediated mitochondrial changes-implications for UV-induced DNA repair and photocarcinogenesis. Cancers 12:5. https://doi.org/10.3390/cancers12010005
Hseu Y-C, Korivi M, Lin F-Y et al (2018) Trans-cinnamic acid attenuates UVA-induced photoaging through inhibition of AP-1 activation and induction of NRF2-mediated antioxidant genes in human skin fibroblasts. J Dermatol Sci 90:123–134. https://doi.org/10.1016/j.jdermsci.2018.01.004
Hseu Y, Chang C-T, Gowrisankar YV (2019) Zerumbone exhibits antiphotoaging and dermatoprotective properties in ultraviolet A-irradiated human skin fibroblast cells via the activation of NRF2/ARE defensive pathway. Oxidative Med Cell Longev 2019:4098674. https://doi.org/10.1155/2019/4098674
Hu J, Yao W, Chang S et al (2022) Structural characterization and anti-photoaging activity of a polysaccharide from Sargassum fusiforme. Food Res Int 157:111267. https://doi.org/10.1016/j.foodres.2022.111267
Hur G-A, Ryu A-R, Kim Y-W et al (2022) The potential anti-photoaging effect of photodynamic therapy using chlorin e6-curcumin conjugate in UVB-irradiated fibroblasts and hairless mice. Pharmaceutics 14:968. https://doi.org/10.3390/pharmaceutics14050968
Hurbain I, Romao M, Sextius P et al (2018) Melanosome distribution in keratinocytes in different skin types: Melanosome clusters are not degradative organelles. J Invest Dermatol 138:647–656. https://doi.org/10.1016/j.jid.2017.09.039
Hwang BM, Noh EM, Kim JS et al (2013) Decursin inhibits UVB-induced MMP expression in human dermal fibroblasts via regulation of nuclear factor-κB. Int J Mol Med 31(2):477–483. https://doi.org/10.3892/ijmm.2012.1202
Jenster L-M, Lange K-E, Normann S et al (2023) P38 kinases mediate NLRP1 inflammasome activation after ribotoxic stress response and virus infection. J Exp Med 220:e20220837. https://doi.org/10.1084/jem.20220837
** Y, Cheng X, Huang X et al (2020) The role of Hrd1 in ultraviolet (UV) radiation induced photoaging. Aging-US 12:21. https://doi.org/10.18632/aging.103851
Kandan P, Balupillai A, Kanimozhi G et al (2020) Opuntiol prevents photoaging of mouse skin via blocking inflammatory responses and collagen degradation. Oxidative Med Cell Longev 2020:5275178. https://doi.org/10.1155/2020/5275178
Kang W, Choi D, Park T (2020) Decanal protects against UVB-induced photoaging in human dermal fibroblasts via the cAMP pathway. Nutrients 12:1214. https://doi.org/10.3390/nu12051214
Katayoshi T, Nakajo T, Tsuji-Naito K (2021) Restoring NAD+ by NAMPT is essential for the SIRT1/p53-mediated survival of UVA- and UVB-irradiated epidermal keratinocytes. J Photochem Photobiol B-Biol 221:112238. https://doi.org/10.1016/j.jphotobiol.2021.112238
Kim H, Jeong Y, Kim J et al (2018) 3,5,6,7,8,3/,4/-Heptamethoxyflavone, a citrus flavonoid, inhibits collagenase activity and induces type I procollagen synthesis in HDFn cells. Int J Mol Sci 19:620. https://doi.org/10.3390/ijms19020620
Kim J-A, Lee J-E, Kim JH (2019) Penta-1,2,3,4,6-O-galloyl-β-d-glucose inhibits UVB-induced photoaging by targeting PAK1 and JNK1. Antioxidants 8:561. https://doi.org/10.3390/antiox8110561
Kim J, Chung K, Yoon Y et al (2022a) Dieckol isolated from Eisenia bicyclis ameliorates wrinkling and improves skin hydration via MAPK/AP-1 and TGF-β/Smad signaling pathways in UVB-irradiated hairless mice. Mar Drugs 20:779. https://doi.org/10.3390/md20120779
Kim KS, Choi YJ, Jang DS et al (2022b) 2-O-β-D-Glucopyranosyl-4,6-dihydroxybenzaldehyde Isolated from Morus alba (Mulberry) fruits suppresses damage by regulating oxidative and inflammatory responses in TNF-α-induced human dermal fibroblasts. Int J Mol Sci 23:14802. https://doi.org/10.3390/ijms232314802
Koenig U, Robenek H, Barresi C et al (2020) Cell death induced autophagy contributes to terminal differentiation of skin and skin appendages. Autophagy 16:932–945. https://doi.org/10.1080/15548627.2019.1646552
Koycheva IK, Marchev AS, Stoykova ID et al (2023) Natural alternatives targeting psoriasis pathology and key signaling pathways: a focus on phytochemicals. Phytochem Rev. https://doi.org/10.1007/s11101-023-09886-9
Kruglikov IL, Zhang Z, Scherer PS (2019) Caveolin-1 in skin aging—from innocent bystander to major contributor. Ageing Res Rev 55:100959. https://doi.org/10.1016/j.arr.2019.100959
Lee H, Kong G, Park J et al (2022a) The potential inhibitory effect of ginsenoside Rh2 on mitophagy in UV-irradiated human dermal fibroblasts. J Ginseng Res 46:646–656. https://doi.org/10.1016/j.jgr.2022.02.001
Lee T, Huang Y-T, Hsiao P-F et al (2022b) Critical roles of irradiance in the regulation of UVB-induced inflammasome activation and skin inflammation in human skin keratinocytes. J Photochem Photobiol B-Biol 226:112373. https://doi.org/10.1016/j.jphotobiol.2021.112373
Li Y-F, Ouyang S-H, Tu L-F et al (2018) Caffeine protects skin from oxidative stress-induced senescence through the activation of autophagy. Theranostics 8:5713–5730. https://doi.org/10.7150/thno.28778
Li Q, Bai D, Qin L et al (2020) Protective effect of D-tetramannuronic acid tetrasodium salt on UVA-induced photo-aging in HaCaT cells. Biomed Pharmacother 126:110094. https://doi.org/10.1016/j.biopha.2020.110094
Li M, Lyu X, Liao J (2022) Rho kinase regulates neutrophil NET formation that is involved in UVB-induced skin inflammation. Theranostics 12:2133–2149. https://doi.org/10.7150/thno.66457
Li C, Zhu Y, Liu W et al (2023) Increased mitochondrial fission induces NLRP3/cGAS-STING mediated pro-inflammatory pathways and apoptosis in UVB-irradiated immortalized human keratinocyte HaCaT cells. Arch Biochem Biophys 738:109558. https://doi.org/10.1016/j.abb.2023.109558
Lin S, Li L, Li M et al (2019) Raffinose increases autophagy and reduces cell death in UVB-irradiated keratinocytes. J Photochem Photobiol B-Biol 201:111653. https://doi.org/10.1016/j.jphotobiol.2019.111653
Liu W, Wang F, Li C et al (2022a) Silibinin relieves UVB-induced apoptosis of human skin cells by inhibiting the YAP-p73 pathway. Acta Pharmacol Sin 43:2156–2167. https://doi.org/10.1038/s41401-021-00826-x
Liu X-Y, Li H, Hwang E et al (2022b) Chemical distance measurement and system pharmacology approach uncover the novel protective effects of biotransformed ginsenoside C-Mc against UVB-irradiated photoaging. Oxidative Med Cell Longev 2022:4691576. https://doi.org/10.1155/2022/4691576
Lone NA, Malik TA, Naikoo SH et al (2020) Trigonelline, a naturally occurring alkaloidal agent protects ultraviolet-B (UV-B) irradiation induced apoptotic cell death in human skin fibroblasts via attenuation of oxidative stress, restoration of cellular calcium homeostasis and prevention of endoplasmic reticulum (ER) stress. J Photochem Photobiol B-Biol 202:111720. https://doi.org/10.1016/j.jphotobiol.2019.111720
Mariño G, Niso-Santan M, Baehrecke E et al (2014) Self-consumption: the interplay of autophagy and apoptosis. Nat Rev Mol Cell Biol 15:84–94. https://doi.org/10.1038/nrm3735
Martic I, Wedel S, Jansen-Dürr P et al (2020) A new model to investigate UVB-induced cellular senescence and pigmentation in melanocytes. Mech Ageing Dev 190:111322. https://doi.org/10.1016/j.mad.2020.111322
Martínez-Gutiérrez A, Fernández-Duran I, Marazuela-Duque A et al (2021) Shikimic acid protects skin cells from UV-induced senescence through activation of the NAD+-dependent deacetylase SIRT1. Aging-US 13:12308–12333. https://doi.org/10.18632/aging.203010
Mei M, Cai R, Yu Q et al (2023) Salidroside alleviates UVB-induced skin damage by inhibiting keratinocytes pyroptosis via the AQP3/ROS/GSDMD-N signaling pathway. J Funct Foods 107:105647. https://doi.org/10.1016/j.jff.2023.105647
Merecz-Sadowska A, Sitarek P, Zajdel K et al (2021) The modulatory influence of plant-derived compounds on human keratinocyte function. Int J Mol Sci 22:12488. https://doi.org/10.3390/ijms222212488
Moon H, Donahue LR, Choi E et al (2017) Melanocyte stem cell activation and translocation initiate cutaneous melanoma in response to UV exposure. Cell Stem Cell 21:665–678. https://doi.org/10.1016/j.stem.2017.09.001
Moya IM, Halder G (2019) Hippo-YAP/TAZ signalling in organ regeneration and regenerative medicine. Nat Rev Mol Cell Biol 20:211–226. https://doi.org/10.1038/s41580-018-0086-y
Mu J, Ma H, Chen H et al (2021) Luteolin prevents UVB-induced skin photoaging damage by modulating SIRT3/ROS/MAPK signaling: an in vitro and in vivo studies. Front Pharmacol 12:728261. https://doi.org/10.3389/fphar.2021.728261
Mu J, Chen H, Ye M (2022) Acacetin resists UVA photoaging by mediating the SIRT3/ROS/MAPKs pathway. J Cell Mol Med 26:4624–4628. https://doi.org/10.1111/jcmm.17415
Muzaffer U, Paul VI, Prasad NR et al (2018) Protective effect of Juglans regia L. against ultraviolet B radiation induced inflammatory responses in human epidermal keratinocytes. Phytomedicine 42:100–111. https://doi.org/10.1016/j.phymed.2018.03.024
Narzt MS, Nagelreiter IM, Oskolkova O et al (2019) A novel role for NUPR1 in the keratinocyte stress response to UV oxidized phospholipids. Redox Biol 20:467–482. https://doi.org/10.1016/j.redox.2018.11.006
Natarajan VT, Ganju P, Ramkumar A et al (2014) Multifaceted pathways protect human skin from UV radiation. Nat Chem Biol 10:542–551. https://doi.org/10.1038/nchembio.1548
Nisar MF, Liu T, Wang M et al (2022) Eriodictyol protects skin cells from UVA irradiation-induced photodamage by inhibition of the MAPK signaling pathway. J Photochem Photobiol B-Biol 226:112350. https://doi.org/10.1016/j.jphotobiol.2021.112350
Noh D, Choi JG, Huh E et al (2018) Tectorigenin, a flavonoid-based compound of leopard lily rhizome, attenuates UV-B-induced apoptosis and collagen degradation by inhibiting oxidative stress in human keratinocytes. Nutrients 10:1998. https://doi.org/10.3390/nu10121998
Oh JH, Joo YH, Karadeniz F et al (2020a) Syringaresinol inhibits UVA-induced MMP-1expression by suppression of MAPK/AP-1 signaling in HaCaT keratinocytes and human dermal fibroblasts. Int J Mol Sci 21:3981. https://doi.org/10.3390/ijms21113981
Oh JH, Karadeniz F, Lee JI et al (2020b) Anticatabolic and anti-inflammatory effects of myricetin 3-O-β-d-galactopyranoside in UVA-irradiated dermal cells via repression of MAPK/AP-1 and activation of TGFβ/Smad. Molecules 25:1331. https://doi.org/10.3390/molecules25061331
Oh JH, Karadeniz F, Kong C-S (2020c) Antiphotoaging effect of 3,5-dicaffeoyl-epi-quinic acid against UVA-induced skin damage by protecting human dermal fibroblasts in vitro. Int J Mol Sci 21:7756. https://doi.org/10.3390/ijms21207756
Oh JH, Kim J, Karadeniz F et al (2021) Santamarine shows anti-photoaging properties via inhibition of MAPK/AP-1 and stimulation of TGF-β/Smad signaling in UVA-irradiated HDFs. Molecules 26:3585. https://doi.org/10.3390/molecules26123585
Oliveira MM, Ratti BA, Daré RG et al (2019) Dihydrocaffeic acid prevents UVB-induced oxidative stress leading to the inhibition of apoptosis and MMP-1 expression via p38 signaling pathway. Oxidative Med Cell Longev 2019:2419096. https://doi.org/10.1155/2019/2419096
Orioli D, Dellambra E (2018) Epigenetic regulation of skin cells in natural aging and premature aging diseases. Cells 7:268. https://doi.org/10.3390/cells7120268
Rice G, Rompolas P (2020) Advances in resolving the heterogeneity and dynamics of keratinocyte differentiation. Curr Opin Cell Biol 67:92–98. https://doi.org/10.1016/j.ceb.2020.09.004
Robinson KS, Toh GA, Rozario P et al (2022) ZAKα-driven ribotoxic stress response activates the human NLRP1 inflammasome. Science 377:6603. https://doi.org/10.1126/science.abl6324
Rusu A, Tanase C, Pascu G-A et al (2020) Recent advances regarding the therapeutic potential of adapalene. Pharmaceuticals 13:217. https://doi.org/10.3390/ph13090217
Sánchez-Marzo N, Pérez-Sánchez A, Barrajón-Catalán E et al (2020) Rosemary diterpenes and flavanone aglycones provide improved genoprotection against UV-induced DNA damage in a human skin cell model. Antioxidants 9:255. https://doi.org/10.3390/antiox9030255
Sand J, Haertel E, Biedermann T et al (2018) Expression of inflammasome proteins and inflammasome activation occurs in human, but not in murine keratinocytes. Cell Death Dis 9:24. https://doi.org/10.1038/s41419-017-0009-4
Shin EJ, Lee JS, Hong S et al (2019a) Quercetin directly targets JAK2 and PKCδ and prevents UV-induced photoaging in human skin. Int J Mol Sci 20:5262. https://doi.org/10.3390/ijms20215262
Shin EJ, Jo S, Choi H-K (2019b) Caffeic acid phenethyl ester inhibits UV-induced MMP-1 expression by targeting histone acetyltransferases in human skin. Int J Mol Sci 20:3055. https://doi.org/10.3390/ijms20123055
Silva L, Perasolia F, Carvalhoa K et al (2020) Melaleuca leucadendron (L.) L. flower extract exhibits antioxidant and photoprotective activities in human keratinocytes exposed to ultraviolet B radiation. Free Radic Biol Med 159:54–65. https://doi.org/10.1016/j.freeradbiomed.2020.07.022
Sirerol JA, Feddi F, Mena S (2015) Topical treatment with pterostilbene, a natural phytoalexin, effectively protects hairless mice against UVB radiation-induced skin damage and carcinogenesis. Free Radic Biol Med 85:1–11. https://doi.org/10.1016/j.freeradbiomed.2015.03.027
Song C, Zhang W, **ao T et al (2023) Reduction of miR-133a-3p contributes to apoptosis and gasdermin E-mediated pyroptosis of keratinocytes in skin exposed to ultraviolet B radiation. J Photochem Photobiol B-Biol 238:112613. https://doi.org/10.1016/j.jphotobiol.2022.112613
Su W, Wang L, Fu X et al (2020) Protective effect of a fucose-rich fucoidan isolated from Saccharina japonica against ultraviolet B-induced photodamage in vitro in human keratinocytes and in vivo in zebrafish. Mar Drugs 18:316. https://doi.org/10.3390/md18060316
Takaya K, Asou T, Kishi K (2023) New senolysis approach via antibody–drug conjugate targeting of the senescent cell marker apolipoprotein D for skin rejuvenation. Int J Mol Sci 24:5857. https://doi.org/10.3390/ijms24065857
Tanveer MA, Rashid H, Nazir LA et al (2023) Trigonelline, a plant derived alkaloid prevents ultraviolet-B-induced oxidative DNA damage in primary human dermal fibroblasts and BALB/c mice via modulation of phosphoinositide 3-kinase-Akt-Nrf2 signalling axis. Exp Gerontol 171:112028. https://doi.org/10.1016/j.exger.2022.112028
Vats K, Kruglov O, Mizes A et al (2021) Keratinocyte death by ferroptosis initiates skin inflammation after UVB exposure. Redox Biol 47:102143. https://doi.org/10.1016/j.redox.2021.102143
Victorelli S, Lagnado A, Halim J et al (2019) Senescent human melanocytes drive skin ageing via paracrine telomere dysfunction. Embo J 38:101982. https://doi.org/10.15252/embj.2019101982
Wang P-W, Hung Y-C, Lin T-Y et al (2019) Comparison of the biological impact of UVA and UVB upon the skin with functional proteomics and immunohistochemistry. Antioxidants 8:569. https://doi.org/10.3390/antiox8120569
Wang M, Lei M, Chang L et al (2021) Bach2 regulates autophagy to modulate UVA-induced photoaging in skin fibroblasts. Free Radic Biol Med 169:304–316. https://doi.org/10.1016/j.freeradbiomed.2021.04.003
Wang Y, Ouyang Q, Chang X (2022) Anti-photoaging effects of flexible nanoliposomes encapsulated Moringa oleifera Lam. isothiocyanate in UVB-induced cell damage in HaCaT cells. Drug Deliv 29:871–881. https://doi.org/10.1080/10717544.2022.2039802
Wong W, Crane E, Zhang H et al (2022) Pgc-1α controls epidermal stem cell fate and skin repair by sustaining NAD+ homeostasis during aging. Mol Metab 65:101575. https://doi.org/10.1016/j.molmet.2022.101575
Wu Q, Bai P, Guo H et al (2022) Capsaicin, a phytochemical from chili pepper, alleviates the ultraviolet irradiation-induced decline of collagen in dermal fibroblast via blocking the generation of ROS. Front Pharmacol 13:872912. https://doi.org/10.3389/fphar.2022.872912
**ao Z, Yang S, Liu Y et al (2022) A novel glyceroglycolipid from brown algae Ishige okamurae improve photoaging and counteract inflammation in UVB-induced HaCaT cells. Chem-Biol Interact 351:109737. https://doi.org/10.1016/j.cbi.2021.109737
Xu X, Wang H-Y, Zhang Y et al (2014) Adipose-derived stem cells cooperate with fractional carbon dioxide laser in antagonizing photoaging: a potential role of Wnt and β-catenin signalling. Cell Biosci 4:24. https://doi.org/10.1186/2045-3701-4-24
Xuan SH, Lee NH, Park SN (2019) Atractyligenin, a terpenoid isolated from coffee silverskin, inhibits cutaneous photoaging. J Photochem Photobiol B-Biol 194:166–173. https://doi.org/10.1016/j.jphotobiol.2019.04.002
Xue N, Liu Y, ** J et al (2022) Chlorogenic acid prevents UVA-induced skin photoaging through regulating collagen metabolism and apoptosis in human dermal fibroblasts. Int J Mol Sci 23:6941. https://doi.org/10.3390/ijms23136941
Yamada M, Mohammed Y, Prow TW et al (2020) Advances and controversies in studying sunscreen delivery and toxicity. Adv Drug Deliv Rev 153:72–86. https://doi.org/10.1016/j.addr.2020.02.001
Yan J, Hao M, Han Y (2021) Sesquiterpenes from Oplopanax elatus stems and their anti-photoaging effects by down-regulating matrix metalloproteinase-1 expression via anti-inflammation. Front Chem 9:766041. https://doi.org/10.3389/fchem.2021.766041
Yang H-L, Lee C-L, Korivi M et al (2018) Zerumbone protects human skin keratinocytes against UVA-irradiated damages through NRF2 induction. Biochem Pharmacol 148:130–146. https://doi.org/10.1016/j.bcp.2017.12.014
Yang H-L, Chen S-J, Pandey S et al (2023) The skin hydration and anti-inflammatory potential of zerumbone, a natural sesquiterpene of Zingiber zerumbet, enhanced Src/ERK-mediated HAS-2/AQP-3 and inhibited NFκB/AP-1 expression in UVB-irradiated human keratinocytes. J Funct Foods 111:105890. https://doi.org/10.1016/j.jff.2023.105890
Yin Y, Li W, Son Y-O et al (2013) Quercitrin protects skin from UVB-induced oxidative damage. Toxicol Appl Pharmacol 269:89–99. https://doi.org/10.1016/j.taap.2013.03.015
Young AR, Claveau J, Rossi AB (2017) Ultraviolet radiation and the skin: photobiology and sunscreen photoprotection. J Am Acad Dermatol 76:S100–S109. https://doi.org/10.1016/j.jaad.2016.09.038
Yun C-Y, Roh E, Kim S-H et al (2020) Stem cell factor-inducible MITF-M expression in therapeutics for acquired skin hyperpigmentation. Theranostics 10:340–352. https://doi.org/10.7150/thno.39066
Zhang Z, Zhang Y, **a S et al (2020) Gasdermin E suppresses tumour growth by activating anti-tumour immunity. Nature 579:415–420. https://doi.org/10.1038/s41586-020-2071-9
Zhang C, Gao X, Li M et al (2023) The role of mitochondrial quality surveillance in skin aging: focus on mitochondrial dynamics, biogenesis and mitophagy. Ageing Res Rev 87:101917. https://doi.org/10.1016/j.arr.2023.101917
Zheng H, Zhang M, Luo H et al (2019) Isoorientin alleviates UVB-induced skin injury by regulating mitochondrial ROS and cellular autophagy. Biochem Biophys Res Commun 514:1133–1139. https://doi.org/10.1016/j.bbrc.2019.04.195
Zheng X, Feng M, Wan J et al (2021) Anti-damage effect of theaflavin-3′-gallate from black tea on UVB-irradiated HaCaT cells by photoprotection and maintaining cell homeostasis. J Photochem Photobiol B-Biol 224:112304. https://doi.org/10.1016/j.jphotobiol.2021.112304
Zhu J, Huang X, Yang T et al (2022) An eco-friendly zein nanoparticle as robust cosmetic ingredient ameliorates skin photoaging. Ind Crop Prod 177:114521. https://doi.org/10.1016/j.indcrop.2022.114521
Zou X, Zou D, Li L et al (2022) Multi-omics analysis of an in vitro photoaging model and protective effect of umbilical cord mesenchymal stem cell-conditioned medium. Stem Cell Res Ther 13:435. https://doi.org/10.1186/s13287-022-03137-y
Acknowledgements
This research received funding from the European Union’s Horizon 2020 research and innovation programme, project PlantaSYST (SGA No 739582 under FPA No. 664620), and the BG05M2OP001-1.003-001-C01 project, financed by the European Regional Development Fund through the “Science and Education for Smart Growth” Operational Programme.
Funding
This work was supported by the European Union’s Horizon 2020 research and innovation programme, project PlantaSYST (SGA No 739582 under FPA No. 664620), and the BG05M2OP001-1.003-001-C01 project, financed by the European Regional Development Fund through the “Science and Education for Smart Growth” Operational Programme.
Author information
Authors and Affiliations
Contributions
IDS: conceptualization, methodology, visualization, writing—original draft. IKK: conceptualization, methodology, visualization, writing—original draft. BKB: methodology, visualization, writing—original draft. LVM: conceptualization, methodology, visualization, writing—original draft, review and editing. MIG: conceptualization, supervision, funding acquisition, writing—review and editing.
Corresponding author
Ethics declarations
Conflict of interest
The authors declare that the work on this review paper was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
Additional information
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.
About this article
Cite this article
Stoykova, I.D., Koycheva, I.K., Binev, B.K. et al. Molecular approaches to prevent UV-induced premature skin aging: focus on phytochemicals as photo-protectants. Phytochem Rev (2024). https://doi.org/10.1007/s11101-024-09952-w
Received:
Accepted:
Published:
DOI: https://doi.org/10.1007/s11101-024-09952-w