Natural Product Modulation of Oxidative Stress in the Treatment of Extrinsic Skin Aging: Mechanisms of Action and Future Perspectives

Abstract

Extrinsic skin aging reflects cumulative exposome stressors, dominated by ultraviolet radiation and compounded by pollution and smoking. These inputs converge on oxidative stress, which triggers stress kinases and inflammatory transcriptional programs, elevates matrix metalloproteinases, suppresses collagen-anabolic signaling, and weakens the epidermal barrier. Here, we synthesize natural products that target this cascade and organize them by biological source and chemical scaffold to link structure with mechanisms. We map actions onto two tracks: damage interception by limiting reactive oxygen species (ROS) and stress signaling, including Nrf2-linked defenses and DNA photoprotection, and by restraining activator protein 1 (AP-1), nuclear factor κB (NF-κB), and matrix metalloproteinases (MMPs); and repair enhancement via extracellular matrix (ECM) rebuilding and barrier restoration. We appraise evidence from 2D cells to 3D skin, animal UV models, and human studies, highlight dose and formulation pitfalls, and propose combination regimens pairing UV filters with bioactives. Finally, we close with translational priorities in delivery, stability, standardization, photosafety, and endpoint-driven clinical trials for personalized systems-level prevention.

Keywords

Skin aging / Photoaging / Natural product / Oxidative stress

References

[1] Walker M. Int. J. Pharm.. 2022, 622121850.

[2] Papaccio F, D’Arino A, Caputo S, Bellei B. Antioxidants. 2022, 111121.

[3] Shin S H, Lee Y H, Rho N K, Park K Y. Front. Physiol.. 2023, 141195272.

[4] Franco A C, Aveleira C, Cavadas C. Trends Mol. Med.. 2022, 2897.

[5] Wu H, Yao Z, Li H, Zhang L, Zhao Y, Li Y, Wu Y, Zhang Z, Xie J, Ding F, Zhu H. J. Nanobiotechnol.. 2024, 22307.

[6] Zhang Y, Liu L, Yue L, Huang Y, Wang B, Liu P. Cytokine Growth Factor Rev.. 2024, 7966.

[7] Fan G, Li F, Wang P, Jin X, Liu R. Int. J. Mol. Sci.. 2022, 2315109.

[8] Feng C, Serre C, Chen W, Imbert I, Zhu L, Ling F. Heliyon. 2024, 10e26131.

[9] Bjørklund G, Shanaida M, Lysiuk R, Butnariu M, Peana M, Sarac I, Strus O, Smetanina K, Chirumbolo S. Molecules. 2022, 277084.

[10] Luo Y, Liu X-C, Li Y-J, Wang Y-J, Qiu M-H, Peng X-R. Phytochemistry Reviews. 2025, 251503.

[11] Krutmann J, Schikowski T, Morita A, Berneburg M. J. Invest. Dermatol.. 2021, 1411096.

[12] Krutmann J, Bouloc A, Sore G, Bernard B A, Passeron T. J. Dermatol. Sci.. 2017, 85152.

[13] Finkel T, Holbrook N J. Nature. 2000, 408239.

[14] Flament F, Bazin R, Qiu H, Ye C, Laquieze S, Rubert V, Decroux A, Simonpietri E, Piot B. Clin. Cosmet. Investig. Dermatol.. 2015, 875.

[15] Marionnet C, Pierrard C, Golebiewski C, Bernerd F. PLoS One. 2014, 9e105263.

[16] Bernerd F, Passeron T, Castiel I, Marionnet C. Int. J. Mol. Sci.. 2022, 238243.

[17] Dupont E, Gomez J, Bilodeau D. Int. J. Cosmet. Sci.. 2013, 35224.

[18] Meeran S M, Katiyar N, Singh T, Katiyar S K. Neoplasia. 2009, 11846.

[19] Huang A H, Chien A L. Curr. Dermatol. Rep.. 2020, 922.

[20] Sinha R P, Hader D P. Photochem. Photobiol. Sci.. 2002, 1225.

[21] Liu K, Yu D, Cho Y Y, Bode A M, Ma W, Yao K, Li S, Li J, Bowden G T, Dong Z, Dong Z. Cancer Res.. 2013, 732181.

[22] Beak S M, Lee Y S, Kim J A. Biochimie. 2004, 86425.

[23] Cavinato M, Jansen-Durr P. Exp. Dermatol.. 2017, 9478

[24] Krutmann J, Morita A, Chung J H. J. Invest. Dermatol.. 2012, 132976.

[25] Parrado C, Mercado-Saenz S, Perez-Davo A, Gilaberte Y, Gonzalez S, Juarranz A. Front. Pharmacol.. 2019, 10759.

[26] Vierkotter A, Schikowski T, Ranft U, Sugiri D, Matsui M, Kramer U, Krutmann J. J. Invest. Dermatol.. 2010, 1302719.

[27] Li M, Vierkotter A, Schikowski T, Huls A, Ding A, Matsui M S, Deng B, Ma C, Ren A, Zhang J, Tan J, Yang Y, Jin L, Krutmann J, Li Z, Wang S. J. Dermatol. Sci.. 2015, 79148.

[28] Afaq F, Zaid M A, Pelle E, Khan N, Syed D N, Matsui M S, Maes D, Mukhtar H. J. Invest. Dermatol.. 2009, 1292396.

[29] Huls A, Vierkotter A, Gao W, Kramer U, Yang Y, Ding A, Stolz S, Matsui M, Kan H, Wang S, Jin L, Krutmann J, Schikowski T. J. Invest. Dermatol.. 2016, 1361053.

[30] He X, Gao X, Xie W. Int. J. Mol. Sci.. 2023, 2415930.

[31] Wroblewska J, Dlugosz A, Czarnecki D, Tomaszewicz W, Blaszak B, Szulc J, Wroblewska W. Molecules. 2025, 303111.

[32] Axelsson J, Sundelin T, Ingre M, Van Someren E J, Olsson A, Lekander M. BMJ. 2010, 341c6614.

[33] Pujos M, Chamayou-Robert C, Parat M, Bonnet M, Couret S, Robiolo A, Doucet O. J. Cosmet. Dermatol.. 2025, 24e16634.

[34] Battie C, Jitsukawa S, Bernerd F, Del Bino S, Marionnet C, Verschoore M. Exp. Dermatol.. 2014, 237.

[35] Chen J, Li Y, Zhu Q, Li T, Lu H, Wei N, Huang Y, Shi R, Ma X, Wang X, Sheng J. Mech. Ageing Dev.. 2017, 1641.

[36] Vikram A, Patel S K, Singh A, Pathania D, Ray R S, Upadhyay A K, Dwivedi A. Phytomedicine. 2024, 132155508.

[37] International Union of Pure and Applied Chemistry (IUPAC). IUPAC Compendium of Chemical Terminology. 20255th Ed.

[38] Newman D J, Cragg G M. J. Nat. Prod.. 2020, 83770.

[39] Nahar L, Sarker S D. Sarker S D, Nahar L. Annu. Rep. Med. Chem., Vol. 55. 2020, San Diego, Academic Press

[40] Tomas M, Günal-Köroğlu D, Kamiloglu S, Ozdal T, Capanoglu E. Immun. Ageing. 2025, 225.

[41] Nurkolis F. Pharmacol. Res.. 2025, 218107868.

[42] Zhao Y, Yu C, Zhang J, Yao Q, Zhu X, Zhou X. Int. J. Mol. Med.. 2025, 56210.

[43] Kim D-H, Kim H-H, Kim H-J, Jung H-G, Yu J-M, Lee E-S, Cho Y-H, Kim D-I, An B-J. Molecules. 2014, 196407.

[44] Li L, Chong L, Huang T, Ma Y, Li Y, Ding H. Animal Model. Exp. Med.. 2023, 6183.

[45] Milutinov J, Pavlović N, Ćirin D, Atanacković Krstonošić M, Krstonošić V. Molecules. 2024, 295409.

[46] Staniforth V, Huang W-C, Aravindaram K, Yang N-S. J. Nutr. Biochem.. 2012, 23443.

[47] Hwang E, Park S-Y, Lee H J, Lee T Y, Sun Z-W, Yi T H. Phytother. Res.. 2014, 281778.

[48] Baek B, Lee S H, Kim K, Lim H W, Lim C J. Korean J. Physiol. Pharmacol.. 2016, 20269.

[49] Daré R G, Nakamura C V, Ximenes V F, Lautenschlager S O S. Free Radic. Biol. Med.. 2020, 160342.

[50] Lee S J, Koh J-S, Ha B-J, Boo Y C. J. Korean Soc. Appl. Biol. Chem.. 2010, 53677.

[51] Huang K-F, Ma K-H, Chang Y-J, Lo L-C, Jhap T-Y, Su Y-H, Liu P-S, Chueh S-H. Exp. Dermatol.. 2019, 28568.

[52] Oh M C, Piao M J, Fernando P M, Han X, Madduma Hewage S R, Park J E, Ko M S, Jung U, Kim I G, Hyun J W. Biomol. Ther.. 2016, 24616.

[53] Hu Y, Ma Y, Wu S, Chen T, He Y, Sun J, Jiao R, Jiang X, Huang Y, Deng L, Bai W. Front. Pharmacol.. 2016, 7301

[54] Zhi Q, Lei L, Li F, Zhao J, Yin R, Ming J. J. Funct. Foods. 2020, 64103640.

[55] Hwang Y P, Oh K N, Yun H J, Jeong H G. J. Dermatol. Sci.. 2011, 6123.

[56] Jung S K, Ha S J, Jung C H, Kim Y T, Lee H K, Kim M O, Lee M H, Mottamal M, Bode A M, Lee K W, Dong Z. J. Cell. Mol. Med.. 2016, 20909.

[57] Jung H, Lee E H, Lee T H, Cho M H. Int. J. Mol. Sci.. 2016, 171449.

[58] Shin E J, Lee J S, Hong S, Lim T G, Byun S. Int. J. Mol. Sci.. 2019, 205262.

[59] Lee K M, Lee K W, Jung S K, Lee E J, Heo Y-S, Bode A M, Lubet R A, Lee H J, Dong Z. Biochem. Pharmacol.. 2010, 802042.

[60] Katiyar S K, Matsui M S, Elmets C A, Mukhtar H. Photochem. Photobiol.. 1999, 69148

[61] Lee H J, Im A R, Kim S M, Kang H S, Lee J D, Chae S. BMC Complement. Altern. Med.. 2018, 1839.

[62] Zhang J-A, Yin Z, Ma L-W, Yin Z-Q, Hu Y-Y, Xu Y, Wu D, Permatasari F, Luo D, Zhou B-R. PLoS One. 2014, 9e99703.

[63] Vijayakumar V, Climent E, Enrique M, Lamelas A, Álvarez B, Chenoll E, Naghibi M, Day R. Front. Nutr.. 2025, 121671835.

[64] Rizzo J, Min M, Adnan S, Afzal N, Maloh J, Chambers C J, Fam V, Sivamani R K. Nutrients. 2023, 154113.

[65] Rizwan M, Rodriguez-Blanco I, Harbottle A, Birch-Machin M A, Watson R E B, Rhodes L E. Brit. J. Dermatol.. 2011, 164154.

[66] Stahl W, Eichler O, Sies H, Heinrich U, Wiseman S, Tronnier H. J. Nutr.. 2001, 1311449.

[67] Ćmitek K, Ćmitek J, Rogl Butina M, Hristov H, Pogačnik T, Pravst I. J. Funct. Foods. 2020, 75104265.

[68] Palombo P, Fabrizi G, Ruocco V, Ruocco E, Fluhr J, Roberts R, Morganti P. Skin Pharmacol. Physiol.. 2007, 20199.

[69] Gonzaáez S, Astner S, An W, Pathak M A, Goukassian D. J. Invest. Dermatol.. 2003, 121399.

[70] Tominaga K, Hongo N, Karato M, Yamashita E. Acta Biochim. Pol.. 2012, 5943.

[71] Davinelli S, Nielsen M E, Scapagnini G. Nutrients. 2018, 10522.

[72] Urikura I, Sugawara T, Hirata T. Biosci. Biotechnol. Biochem.. 2011, 75757.

[73] Liu S, Mohri S, Tsukamoto M, Yanai Y, Manabe Y, Sugawara T. J. Sci. Food Agric.. 2025, 105453.

[74] Park M, Han J, Lee C S, Soo B H, Lim K M, Ha H. Exp. Dermatol.. 2013, 22336.

[75] Farrukh M R, Nissar U-A, Kaiser P J, Afnan Q, Sharma P R, Bhushan S, Tasduq S A. J. Photochem. Photobiol. B. 2015, 148351.

[76] Oh J. H., Kim J., Karadeniz F., Kim H. R., Park S. Y., Seo Y., Kong C. S., Molecules, 2021, 26.

[77] Hong Y H, Lee H S, Jung E Y, Han S H, Park Y, Suh H J. J. Ginseng Res.. 2017, 41456.

[78] Li Z, Jiang R, Wang M, Zhai L, Liu J, Xu X, Sun L, Zhao D. J. Ginseng Res.. 2022, 46115.

[79] Li J, Liu D, Wu J, Zhang D, Cheng B, Zhang Y, Yin Z, Wang Y, Du J, Ling C. Sci. Rep.. 2016, 639336.

[80] Huang J, Tu T, Wang W, Zhou G, Zhang W, Wu X, Liu W. Photochem. Photobiol.. 2020, 96124.

[81] Choi Y J, Cho E-C, Lim S, Lee J, Bae J, Oh T K, Lee J K, Kim E J. Int. J. Mol. Sci.. 2026, 27204.

[82] Dhaliwal S, Rybak I, Ellis S R, Notay M, Trivedi M, Burney W, Vaughn A R, Nguyen M, Reiter P, Bosanac S, Yan H, Foolad N, Sivamani R K. Brit. J. Dermatol.. 2019, 180289.

[83] Koo S W, Hirakawa S, Fujii S, Kawasumi M, Nghiem P. Br. J. Dermatol.. 2007, 156957.

[84] Li Y F, Ouyang S H, Tu L F, Wang X, Yuan W L, Wang G E, Wu Y P, Duan W J, Yu H M, Fang Z Z, Kurihara H, Zhang Y, He R R. Theranostics. 2018, 85713.

[85] Kim S, Chung J H. Phytomedicine. 2008, 15749.

[86] Lone A N, Malik A T, Naikoo H S, Raghu R S, S A T. J. Photochem. Photobiol. B. 2020, 202111720.

[87] Hwang J, Kim D, Park J S, Park H J, Shin J, Lee S K. Mar. Drugs. 2020, 1887.

[88] Yuksel Egrilmez M, Kocturk S, Aktan S, Oktay G, Resmi H, Simsek Keskin H, Guner Akdogan G, Ozkan S. Life. 2022, 12950.

[89] Kim Y, Bae K S. Nat. Prod. Commun.. 2019, 141934578X19872425

[90] Yun J, Kim C, Kim M B, Hwang J K. Evid-Based Compl. Alt.. 2018, 20186172954.

[91] Tang G., Chen M., Zhang Y., Qian Z. J., Nat. Prod. Res., 2025, 1.

[92] Feng X, Shang J, Wang Y, Chen Y, Liu Y. Food Sci. Nutr.. 2025, 13e70212.

[93] Wei K, He L, Li X, Wu M, Wang H, Hu L, Xu H, Zhang Y, Zhou L, Xu X, Guo L. Int. J. Biol. Macromol.. 2025, 329147834.

[94] Wen L, Gao Q, Ma C-W, Ge Y, You L, Liu R H, Fu X, Liu D. J. Funct. Foods. 2016, 20400.

[95] Kim Y-I, Oh W-S, Song P H, Yun S, Kwon Y-S, Lee Y J, Ku S-K, Song C-H, Oh T-H. Mar. Drugs. 2018, 16286.

[96] Wang L, Lee W, Oh J Y, Cui Y R, Ryu B, Jeon Y J. Mar. Drugs. 2018, 16239.

[97] Kong S Z, Li D D, Luo H, Li W J, Huang Y M, Li J C, Hu Z, Huang N, Guo M H, Chen Y, Li S D. Exp. Gerontol.. 2018, 10327.

[98] Li Q, Bai D, Qin L, Shao M, Liu X, Zhang S, Yan C, Yu G, Hao J. Int. J. Mol. Sci.. 2020, 211201.

[99] Peng S, Guo C, Wu S, Duan Z. Heliyon. 2022, 8e11125.

[100] Nobile V, Roveda G, Spartà E, Tursi F. Cosmetics. 2025, 1252.

[101] Rhodes L E, Durham B H, Fraser W D, Friedmann P S. J. Invest. Dermatol.. 1995, 105532.

[102] Orengo I F, Black H S, Wolf J EJr.. Arch. Dermatol. Res.. 1992, 284219.

[103] Kawamura A, Ooyama K, Kojima K, Kachi H, Abe T, Amano K, Aoyama T. J. Oleo Sci.. 2011, 60597.

[104] Muggli R. Int. J. Cosmet. Sci.. 2005, 27243.

[105] Koh Y G, Seok J, Park J W, Kim K R, Yoo K H, Kim Y J, Kim B J. Heliyon. 2023, 9e16711.

[106] Wang X, Jia Y, He H. Int. J. Mol. Sci.. 2025, 26246.

[107] Ahn Y, Joo Suh H, Hong K-B, Choi Y, Lee S J, Jung E-J. J. Funct. Foods. 2024, 113106008.

[108] Bizot V, Cestone E, Michelotti A, Nobile V. Cosmetics. 2017, 437.

[109] Yan L, Liu Z, Zeng Y, Ji X, Wang H, Ni D, Pan M. J. Nanobiotechnol.. 2025, 23142.

[110] Wolosik K, Chalecka M, Gasiewska G, Palka J, Surazynski A. Molecules. 2025, 301964.

[111] Kim M S, Oh G H, Kim M J, Hwang J K. Photochem. Photobiol.. 2013, 89911.

[112] Hwang E, Park S Y, Sun Z W, Shin H S, Lee D G, Yi T H. Mar. Biotechnol.. 2014, 16361.

[113] Lee H, Sung J, Kim Y, Jeong H S, Lee J. Antioxidants. 2019, 8644.

[114] Melo C P B, Saito P, Martinez R M, Staurengo-Ferrari L, Pinto I C, Rodrigues C C A, Badaro-Garcia S, Vignoli J A, Baracat M M, Bussmann A J C, Georgetti S R, Verri W A, Casagrande R. Molecules. 2023, 282417.

[115] Ren C, Ma Y, Wang Y, Luo D, Hong Y, Zhang X, Mei H, Liu W. Pharmaceutics. 2024, 16876.

[116] Myung S K, Park Y. Am. J. Med.. 2025, 1381264.

[117] Choi S Y, Ko E J, Lee Y H, Kim B G, Shin H J, Seo D B, Lee S J, Kim B J, Kim M N. J. Cosmet. Laser Ther.. 2014, 16132.

[118] Nagae M, Nishio T, Ohnuki K, Shimizu K. Health Sci. Rep.. 2022, 5e522.

[119] Katayoshi T, Yamaura N, Nakajo T, Kitajima N, Tsuji-Naito K. Sci. Rep.. 2022, 1219040.

[120] Choi Y J, Kang M, Jin M H, Kim J, Lee W K, Roh S S, Kang K S, Hwang G S, Park S, Lee S. Curr. Issues Mol. Biol.. 2025, 47941.

[121] Hahm K M, Park S-H, Oh S W, Kim J H, Yeom H S, Lee H J, Yang S, Cho J Y, Park J O, Lee J. Molecules. 2021, 266074.

[122] Oh S W, Yu E, Kwon K, Lee H J, Yeom H S, Hahm K M, Park J O, Cho J Y, Lee J. Biomater. Sci.. 2025, 134264.

[123] Xu D, Li C, Zhao M. Mar. Drugs. 2022, 20252.

[124] Pickart L, Margolina A. Int. J. Mol. Sci.. 2018, 191987.

[125] Pickart L, Vasquez-Soltero J M, Margolina A. Biomed. Res. Int.. 2015, 2015648108.

[126] Narda M, Peno-Mazzarino L, Krutmann J, Trullas C, Granger C. Skin Pharmacol. Physiol.. 2018, 31324.

[127] Dissette V, Bignozzi C A, Valacchi G, Pecorelli A, Manfredini S, Vertuani S. Cosmetics. 2018, 567.

[128] Liu T, Zhu S, Yang Y, Qin W, Wang Z, Zhao Z, Liu T, Wang X, Duan T, Liu Y, Liu Y, Xia Q, Zhang H, Li N. Biomed. Pharmacother.. 2024, 171116110.

[129] Klinngam W, Rungkamoltip P, Wongwanakul R, Joothamongkhon J, Du-a-man S, Khongkow M, Asawapirom U, Iempridee T, Ruktanonchai U. Biomolecules. 2024, 14776.

[130] Liu S, Sui Q, Zou J, Zhao Y, Chang X. J. Food Biochem.. 2019, 43e12708.

[131] Li L, Huang T, Lan C, Ding H, Yan C, Dou Y. J. Photochem. Photobiol. B. 2019, 191135.

[132] Lin M, Bao C, Chen L, Geng S, Wang H, Xiao Z, Gong T, Ji C, Cheng B. Photochem. Photobiol. Sci.. 2023, 222285.

[133] Nisar M F, Liu T, Wang M, Chen S, Chang L, Karisma V W, WeixuDiao Q, Xue M, Tang X, Pourzand C, Yang J, Zhong J L. J. Photochem. Photobiol. B. 2022, 226112350.

[134] Deng M, Wang J, Li Y-L, Chen H-X, Tai M, Deng L, Che B, Du Z-Y, Dong C-Z, Lin L. J. Cosmet. Dermatol.. 2022, 21781.

[135] Afnan Q, Kaiser P J, Rafiq R A, Nazir L A, Bhushan S, Bhardwaj S C, Sandhir R, Tasduq S A. Exp. Dermatol.. 2016, 25440.

[136] Nam E J, Yoo G, Lee J Y, Kim M, Jhin C, Son Y J, Kim S Y, Jung S H, Nho C W. BMB Rep.. 2020, 53379.

[137] Xu S, Sun X, Zhu Z, Xin Y, Chen C, Luo J. J. Ethnopharmacol.. 2024, 332118352.

[138] He Y-L, Xiao Z, Yang S, Zhou C, Sun S, Hong P, Qian Z-J. Photochem. Photobiol.. 2022, 981131.

[139] Mantena S K, Katiyar S K. Free Radic. Biol. Med.. 2006, 401603.

[140] Kwon Y, Shafi R, Oak A, Athar M, Slominski A, Elmets C A. Photochem. Photobiol.. 2025, 1011392.

[141] Singh R P, Dhanalakshmi S, Mohan S, Agarwal C, Agarwal R. Mol. Cancer Ther.. 2006, 51145.

[142] Hwang E, Ngo H T T, Seo S A, Park B, Zhang M, Yi T-H. Phytomedicine. 2018, 39125.

[143] Hwang E, Gao W, Xiao Y K, Ngo H T T, Yi T H. J. Cell. Biochem.. 2019, 120601.

[144] Wang K, Hu X, Xie X-L, Huang M, Wang D, Yu F-L. J. Ethnopharmacol.. 2024, 334118535.

[145] Piao M J, Kang K A, Ryu Y S, Shilnikova K, Park J E, Hyun Y J, Zhen A X, Kang H K, Koh Y S, Ahn M J, Hyun J W. Mar. Drugs. 2017, 15268.

[146] Wang C, Eskiw C H. Sci. Rep.. 2019, 92932.

[147] Lee S H, Won G-W, Choi S-H, Kim M-Y, Oh C-H, Park J-T, Park J-I. Biomed. Pharmacother.. 2022, 153113311.

[148] Liu Y-H, Lin Y-S, Huang Y-W, Fang S-U, Lin S-Y, Hou W-C. J. Agric. Food. Chem.. 2016, 643598.

[149] Pujimulyani D, Suryani C L, Setyowati A, Handayani R A S, Arumwardana S, Widowati W, Maruf A. Heliyon. 2020, 6e04921.

[150] Khan A, Bai H, Shu M, Chen M, Khan A, Bai Z. Biosci. Rep.. 2018, 38BSR20181414.

[151] Oh S-J, Oh Y, Ryu I W, Kim K, Lim C-J. Biosci. Biotechnol. Biochem.. 2016, 8095.

[152] Buranasudja V, Rani D, Malla A, Kobtrakul K, Vimolmangkang S. Sci. Rep.. 2021, 1113459.

[153] Fernando P D S M, Piao M J, Herath H M U L, Kang K A, Hyun C L, Kim E T, Koh Y S, Hyun J W. Toxicol. In vitro. 2024, 99105870.

[154] Jang L, Choi J, Lee S, Lee S. J. Sci. Food Agric.. 2023, 1033701.

[155] Kim S Y, Kwon Y M, Kim K W, Kim J Y H. Mar. Drugs. 2021, 19690.

[156] Rajnochová Svobodová A, Gabrielová E, Michaelides L, Kosina P, Ryšavá A, Ulrichová J, Zálešák B, Vostálová J. Arch. Dermatol. Res.. 2018, 310413.

[157] Quan T, He T, Kang S, Voorhees J J, Fisher G J. Am. J. Pathol.. 2004, 165741.

[158] Zeng J, An M, Tian W, Wang K, Du B, Li P. J. Sci. Food Agric.. 2023, 1034470.

[159] Mu J, Chen H, Ye M, Zhang X, Ma H. J. Cell. Mol. Med.. 2022, 264624.

[160] Hwang E, Lin P, Ngo H T T, Yi T-H. Food Funct.. 2018, 94936.

[161] Lee J, Jung E, Kim Y, Park J, Park J, Hong S, Kim J, Hyun C, Kim Y S, Park D. Planta Med.. 2006, 72324.

[162] Zhao D, Shi Y, Dang Y, Zhai Y, Ye X. Australas. J. Dermatol.. 2015, 56e7.

[163] Kwok H-H, Yue P Y-K, Mak N-K, Wong R N-S. Biochem. Pharmacol.. 2012, 84532.

[164] Gao W, Wang Y-S, Hwang E, Lin P, Bae J, Seo S A, Yan Z, Yi T-H. J. Photochem. Photobiol. B. 2018, 185241.

[165] Han S H, Ballinger E, Choung S-Y, Kwon J Y. Mar. Drugs. 2022, 20308.

[166] Chaudhuri R K, Bojanowski K. Int. J. Cosmet. Sci.. 2014, 36221.

[167] Man G, Mauro T M, Zhai Y, Kim P L, Cheung C, Hupe M, Crumrine D, Elias P M, Man M Q. J. Invest. Dermatol.. 2015, 1351184.

[168] Hou M, Sun R, Hupe M, Kim P L, Park K, Crumrine D, Lin T K, Santiago J L, Mauro T M, Elias P M, Man M Q. Exp. Dermatol.. 2013, 22210.

[169] Nakahara T, Mitoma C, Hashimoto-Hachiya A, Takahara M, Tsuji G, Uchi H, Yan X, Hachisuka J, Chiba T, Esaki H, Kido-Nakahara M, Furue M. J. Med. Food. 2015, 181143.

[170] Razia S, Park H, Shin E, Shim K-S, Cho E, Kim S-Y. Molecules. 2021, 262626.

[171] Han E J, Kim S-Y, Han H-J, Kim H-S, Kim K-N, Fernando I P S, Madusanka D M D, Dias M K H M, Cheong S H, Park S R, Han Y S, Lee K, Ahn G. Sci. Rep.. 2021, 119963.

[172] Zhang J, Zhong J, Li Y, Zhou Q, Du Z, Lin L, Shu P, Jiang L, Zhou W. Mar. Drugs. 2025, 23445.

[173] Uchiyama T, Nakano Y, Ueda O, Mori H, Nakashima M, Noda A, Ishizaki C, Mizoguchi M. J. Health Sci.. 2008, 54559.

[174] Schuch A P, Moreno N C, Schuch N J, Menck C F M, Garcia C C M. Free Radic. Biol. Med.. 2017, 107110.

[175] Middelkamp-Hup M A, Pathak M A, Parrado C, Goukassian D, Rius-Díaz F, Mihm M C, Fitzpatrick T B, Gonzalez S. J. Am. Acad. Dermatol.. 2004, 51910.

[176] Katiyar S K, Perez A, Mukhtar H. Clin. Cancer Res.. 2000, 63864

[177] Katiyar S K, Mantena S K, Meeran S M. PLoS One. 2011, 6e21410.

[178] Guillermo-Lagae R, Deep G, Ting H, Agarwal C, Agarwal R. Oncotarget. 2015, 639594.

[179] El-Mahdy M A, Zhu Q, Wang Q E, Wani G, Patnaik S, Zhao Q, Arafa el S, Barakat B, Mir S N, Wani A A. Photochem. Photobiol.. 2008, 84307.

[180] Shin S, Kum H, Ryu D, Kim M, Jung E, Park D. Int. J. Mol. Sci.. 2014, 1518919.

[181] Janjetovic Z, Nahmias Z P, Hanna S, Jarrett S G, Kim T K, Reiter R J, Slominski A T. J. Pineal. Res.. 2014, 5790.

[182] Heffernan T P, Kawasumi M, Blasina A, Anderes K, Conney A H, Nghiem P. J. Invest. Dermatol.. 2009, 1291805.

[183] Lu Y P, Lou Y R, Peng Q Y, Xie J G, Nghiem P, Conney A H. Cancer Res.. 2008, 682523.

[184] Schulz K F, Altman D G, Moher D. BMJ. 2010, 340c332.

[185] GRADE Working Group. BMJ. 2004, 3281490.

[186] Lombardi F., Augello F. R., Ciafarone A., Ciummo V., Altamura S., Cinque B., Palumbo P., Biomolecules, 2024, 14.

[187] Co-operation O. F. E.. Test No. 439: In vitro Skin Irritation: Reconstructed Human Epidermis Test Method. 2013, Paris, OECD Publishing

[188] Szilágyi Z, Németh Z, Bakos J, Kubinyi G, Necz P P, Szabó E, Thuróczy G, Pinto R, Selmaoui B. Int. J. Mol. Sci.. 2023, 242853.

[189] Liu Y, Liu J, Dai H, Wang R, Hsiao A, Wang W, Betts R J, Marionnet C, Bernerd F, Qiu J. J. Dermatol. Sci.. 2022, 10537.

[190] Lévéque J L. J. Eur. Acad. Dermatol. Venereol.. 1999, 12103

[191] Rogiers V. Skin Pharmacol. Appl. Skin Physiol.. 2001, 14117.

[192] Percie du Sert N, Hurst V, Ahluwalia A, Alam S, Avey M T, Baker M, Browne W J, Clark A, Cuthill I C, Dirnagl U, Emerson M, Garner P, Holgate S T, Howells D W, Karp N A, Lazic S E, Lidster K, MacCallum C J, Macleod M, Pearl E J, Petersen O H, Rawle F, Reynolds P, Rooney K, Sena E S, Silberberg S D, Steckler T, Würbel H. PLoS Biol.. 2020, 18e3000410.

[193] Hooijmans C R, Rovers M M, de Vries R B, Leenaars M, Ritskes-Hoitinga M, Langendam M W. BMC Med. Res. Methodol.. 2014, 1443.

[194] Zhang X, Chen S, Luo D, Chen D, Zhou H, Zhang S, Chen X, Lu W, Liu W. Molecules. 2023, 282738.

[195] Costa R, Nunes C, Lima S A C, Gameiro P, Reis S. Int. J. Pharm.. 2025, 681125894.

[196] Hamed R, AbuKwiak A D, Aburayya R, Alkilani A Z, Hamadneh L, Naser M, Al-Adhami Y, Alhusban A A. Heliyon. 2024, 10e37381.

[197] Shin J Y, Han D, Yoon K Y, Jeong D H, Park Y I. Ann. Dermatol.. 2024, 36215.

[198] OECD T. N.. OECD Guidel. Test. Chem.. 2015, 41

[199] Bråred Christensson J, Hagvall L, Karlberg A-T. Cosmetics. 2016, 319.

[200] De Smedt A. In vitro 3T3 NRU Phototoxicity Test. Oral Communication During the Annual Conference 2007 of the European Partnership for Alternative Approaches to Animal Testing. 2007

[201] Burnett C L, Fiume M M, Bergfeld W F, Belsito D V, Hill R A, Klaassen C D, Liebler D C, Marks J GJrShank R C, Slaga T J. Int. J. Toxicol.. 2019, 3833S.

[202] Irizar A, Boislève F, Gautier F, Nash J F, Pfuhler S, Ritacco G, Vey M, Wolf N, Cadby P A. Food Chem. Toxicol.. 2025, 200115332.

[203] Wölfle U, Seelinger G, Schempp C M. Planta Med.. 2014, 80109.

[204] Barthe M, Bavoux C, Finot F, Mouche I, Cuceu-Petrenci C, Forreryd A, Chérouvrier Hansson A, Johansson H, Lemkine G F, Thénot J-P, Osman-Ponchet H. Cosmetics. 2021, 850.

[205] Lin F-H, Lin J-Y, Gupta R D, Tournas J A, Burch J A, Angelica Selim M, Monteiro-Riviere N A, Grichnik J M, Zielinski J, Pinnell S R. J. Invest. Dermatol.. 2005, 125826.

[206] Murray J C, Burch J A, Streilein R D, Iannacchione M A, Hall R P, Pinnell S R. J. Am. Acad. Dermatol.. 2008, 59418.

[207] Alvares B A, Miola A C, Schimitt J V, Miot H A, Abbade L P F. An. Bras. Dermatol.. 2022, 97157.

[208] Krutmann J, Schikowski T, Morita A, Berneburg M. J. Invest. Dermatol.. 2021, 1411096.

[209] Krutmann J, Bouloc A, Sore G, Bernard B A, Passeron T. J. Dermatol. Sci.. 2017, 85152.

[210] Haykal D. Front. Digit. Health. 2025, 71534859.

[211] Haykal D, Flament F, Amar D, Cartier H, Kourosh A S, Lee D H, Rowland-Payne C. Front. Artif. Intell.. 2025, 81660356.

[212] Lee C. H., Lee S. H., Biomolecules, 2025, 15.

[213] Zhang W, Guo H, Li L, Zhang M, Xu E, Dai L. ACS Omega. 2024, 931878.

RIGHTS & PERMISSIONS

Jilin University, The Editorial Department of Chemical Research in Chinese Universities and Springer-Verlag GmbH