{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,5]],"date-time":"2026-03-05T23:50:50Z","timestamp":1772754650896,"version":"3.50.1"},"reference-count":58,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2019,8,1]],"date-time":"2019-08-01T00:00:00Z","timestamp":1564617600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Marine Drugs"],"abstract":"<jats:p>Excessive exposure to ultraviolet (UV) radiation is the main risk factor to develop skin pathologies or cancer because it encourages oxidative condition and skin inflammation. In this sense, strategies for its prevention are currently being evaluated. Natural products such as carotenoids or polyphenols, which are abundant in the marine environment, have been used in the prevention of oxidative stress due to their demonstrated antioxidant activities. Nevertheless, the anti-inflammatory activity and its implication in photo-prevention have not been extensively studied. Thus, we aimed to evaluate the combination of fucoxanthin (FX) and rosmarinic acid (RA) on cell viability, apoptosis induction, inflammasome regulation, and anti-oxidative response activation in UVB-irradiated HaCaT keratinocytes. We demonstrated for the first time that the combination of FX and RA (5 \u00b5M RA plus 5 \u03bcM FX, designated as M2) improved antioxidant and anti-inflammatory profiles in comparison to compounds assayed individually, by reducing UVB-induced apoptosis and the consequent ROS production. Furthermore, the M2 combination modulated the inflammatory response through down-regulation of inflammasome components such as NLRP3, ASC, and Caspase-1, and the interleukin (IL)-1\u03b2 production. In addition, Nrf2 and HO-1 antioxidant genes expression increased in UVB-exposed HaCaT cells pre-treated with M2. These results suggest that this combination of natural products exerts photo-protective effects by down-regulating NRLP3-inflammasome and increasing Nrf2 signalling pathway.<\/jats:p>","DOI":"10.3390\/md17080451","type":"journal-article","created":{"date-parts":[[2019,8,1]],"date-time":"2019-08-01T11:39:37Z","timestamp":1564659577000},"page":"451","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":83,"title":["Fucoxanthin and Rosmarinic Acid Combination Has Anti-Inflammatory Effects through Regulation of NLRP3 Inflammasome in UVB-Exposed HaCaT Keratinocytes"],"prefix":"10.3390","volume":"17","author":[{"given":"Azahara","family":"Rodr\u00edguez-Luna","sequence":"first","affiliation":[{"name":"Department of Pharmacology, Faculty of Pharmacy, Universidad de Sevilla,  41012 Seville, Spain"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9766-8178","authenticated-orcid":false,"given":"Javier","family":"\u00c1vila-Rom\u00e1n","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Faculty of Pharmacy, Universidad de Sevilla,  41012 Seville, Spain"}]},{"given":"Helena","family":"Oliveira","sequence":"additional","affiliation":[{"name":"Department of Biology, Faculty of Biology, University of Aveiro,  3810-193 Aveiro, Portugal"}]},{"given":"Virginia","family":"Motilva","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Faculty of Pharmacy, Universidad de Sevilla,  41012 Seville, Spain"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9955-801X","authenticated-orcid":false,"given":"Elena","family":"Talero","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Faculty of Pharmacy, Universidad de Sevilla,  41012 Seville, Spain"}]}],"member":"1968","published-online":{"date-parts":[[2019,8,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1111\/phpp.12348","article-title":"Topical Application of Nexrutine Inhibits UVB-induced Cutaneous Inflammatory Responses in SKH-1 Hairless Mouse","volume":"34","author":"Alam","year":"2018","journal-title":"Photodermatol. Photoimmunol. Photomed."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1016\/j.semcancer.2017.04.003","article-title":"Dietary Proanthocyanidins Prevent Ultraviolet Radiation-Induced Non-Melanoma Skin Cancer Through Enhanced Repair of Damaged DNA-Dependent Activation of Immune Sensitivity","volume":"46","author":"Katiyar","year":"2017","journal-title":"Semin. Cancer Biol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2937","DOI":"10.4049\/jimmunol.1601681","article-title":"Anti-Inflammatory Role of Langerhans Cells and Apoptotic Keratinocytes in Ultraviolet-B-Induced Cutaneous Inflammation","volume":"199","author":"Hatakeyama","year":"2017","journal-title":"J. Immunol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"8379539","DOI":"10.1155\/2017\/8379539","article-title":"Resveratrol-Enriched Rice Attenuates UVB-ROS-Induced Skin Aging Via Downregulation of Inflammatory Cascades","volume":"2017","author":"Subedi","year":"2017","journal-title":"Oxid. Med. Cell. Longev."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1111\/j.1600-0625.1994.tb00263.x","article-title":"Differential Modulation of Interleukin-1 Alpha (IL-1\u03b1) and Interleukin-1 beta (IL-1\u03b2) in Human Epidermal Keratinocytes by UVB","volume":"3","author":"Kondo","year":"1994","journal-title":"Exp. Dermatol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1140","DOI":"10.1016\/j.cub.2007.05.074","article-title":"The Inflammasome Mediates UVB-Induced Activation and Secretion of Interleukin-1\u03b2 by Keratinocytes","volume":"17","author":"Feldmeyer","year":"2007","journal-title":"Curr. Biol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1016\/j.bbrc.2016.06.106","article-title":"Nuclear DNA Damage-Triggered NLRP3 Inflammasome Activation Promotes UVB-Induced Inflammatory Responses in Human Keratinocytes","volume":"477","author":"Hasegawa","year":"2016","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1025","DOI":"10.1111\/php.12725","article-title":"Ultraviolet Radiation-Induced Downregulation of SERCA2 Mediates Activation of NLRP3 Inflammasome in Basal Cell Carcinoma","volume":"93","author":"Ahmad","year":"2017","journal-title":"Photochem. Photobiol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1186\/s13046-017-0589-y","article-title":"NLRP3 Inflammasome Activation Promotes Inflammation-Induced Carcinogenesis in Head and Neck Squamous Cell Carcinoma","volume":"36","author":"Huang","year":"2017","journal-title":"J. Exp. Clin. Cancer Res."},{"key":"ref_10","first-page":"w14380","article-title":"Non-Melanoma Skin Cancer in Mountain Guides: High Prevalence and Lack of Awareness Warrant Development of Evidence-Based Prevention Tools","volume":"146","author":"Zink","year":"2016","journal-title":"Swiss Med. Wkly."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"6152","DOI":"10.3390\/md13106152","article-title":"Bioactive Compounds Isolated from Microalgae in Chronic Inflammation and Cancer","volume":"13","author":"Talero","year":"2015","journal-title":"Mar. Drugs"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"787042","DOI":"10.1155\/2013\/787042","article-title":"Radical Scavenging Activity-Based and AP-1-Targeted Anti-Inflammatory Effects of Lutein in Macrophage-Like and Skin Keratinocytic Cells","volume":"2013","author":"Oh","year":"2013","journal-title":"Mediat. Inflamm."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Yoshihisa, Y., Andoh, T., Matsunaga, K., Rehman, M.U., Maoka, T., and Shimizu, T. (2016). Efficacy of Astaxanthin for the Treatment of Atopic Dermatitis in a Murine Model. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0152288"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1134","DOI":"10.1016\/j.funbio.2018.07.007","article-title":"Microbial and Pigment Profile of the Reddish Patch Occurring within Tuber Magnatum Ascomata","volume":"122","author":"Amicucci","year":"2018","journal-title":"Fungal Biol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"604","DOI":"10.3390\/md10030604","article-title":"Fucoxantin: A Treasure from the Sea","volume":"10","author":"Gemello","year":"2012","journal-title":"Mar. Drugs"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Saric, S., and Sivamani, R. (2016). Polyphenols and Sunburn. Int. J. Mol. Sci., 17.","DOI":"10.3390\/ijms17091521"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1007\/s11101-013-9282-8","article-title":"Rosmarinic Acid: New Aspects","volume":"12","author":"Petersen","year":"2013","journal-title":"Phytochem. Rev."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2729","DOI":"10.3390\/md10122729","article-title":"Rosmarinic Acid from Eelgrass Shows Nematicidal and Antibacterial Activities Against Pine Wood Nematode and Its Carrying Bacteria","volume":"10","author":"Wang","year":"2012","journal-title":"Mar. Drugs"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"867","DOI":"10.1080\/08927014.2017.1383399","article-title":"Identification of Rosmarinic Acid and Sulfated Flavonoids as Inhibitors of Microfouling on the Surface of Eelgrass Zostera Marina","volume":"33","author":"Guan","year":"2017","journal-title":"Biofouling"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"388","DOI":"10.1055\/s-0035-1568274","article-title":"Rosmarinic Acid-Pharmaceutical and Clinical Aspects","volume":"82","author":"Amoah","year":"2016","journal-title":"Planta Med."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1016\/j.lfs.2016.05.023","article-title":"Rosmarinic Acid Inhibits Poly(I:C)-Induced Inflammatory Reaction of Epidermal Keratinocytes","volume":"155","author":"Zhou","year":"2016","journal-title":"Life Sci."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"732","DOI":"10.1007\/s10753-017-0728-9","article-title":"Rosmarinic Acid Mitigates Lipopolysaccharide-Induced Neuroinflammatory Responses through the Inhibition of TLR4 and CD14 Expression and NF-\u03baB and NLRP3 Inflammasome Activation","volume":"41","author":"Wei","year":"2018","journal-title":"Inflammation"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1758","DOI":"10.1002\/jcp.27046","article-title":"Rosmarinic Acid Inhibits Nicotine-Induced C-Reactive Protein Generation by Inhibiting NLRP3 Inflammasome Activation in Smooth Muscle Cells","volume":"234","author":"Yao","year":"2019","journal-title":"J. Cell. Physiol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1016\/j.jdermsci.2009.01.005","article-title":"Keratinocyte Growth Factor Down-Regulates Intracellular ROS Production Induced by UVB","volume":"54","author":"Kovacs","year":"2009","journal-title":"J. Dermatol. Sci."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"2973","DOI":"10.1042\/BCJ20160471","article-title":"Molecular Signaling Cascades Involved in Nonmelanoma Skin Carcinogenesis","volume":"473","author":"Feehan","year":"2016","journal-title":"Biochem. J."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"8214631","DOI":"10.1155\/2016\/8214631","article-title":"The Effect of Lycopene Preexposure on UV-B-Irradiated Human Keratinocytes","volume":"2016","author":"Ascenso","year":"2016","journal-title":"Oxid. Med. Cell. Longev."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1016\/j.jphotobiol.2017.05.042","article-title":"Protective Effect of Arthrospira platensis Extracts Against Ultraviolet B-Induced Cellular Senescence Through Inhibition of DNA Damage and Matrix Metalloproteinase-1 Expression in Human Dermal Fibroblasts","volume":"173","author":"Lee","year":"2017","journal-title":"J. Photochem. Photobiol. B Biol."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Furue, M., Uchi, H., Mitoma, C., Hashimoto-Hachiya, A., Chiba, T., Ito, T., Nakahara, T., and Tsuji, G. (2017). Antioxidants for Healthy Skin: The Emerging Role of Aryl Hydrocarbon Receptors and Nuclear Factor-Erythroid 2-Related Factor-2. Nutrients, 9.","DOI":"10.3390\/nu9030223"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"7340143","DOI":"10.1155\/2017\/7340143","article-title":"Antioxidant and Anti-Inflammatory Effects of Shungite Against Ultraviolet B Irradiation-Induced Skin Damage in Hairless Mice","volume":"2017","author":"Sajo","year":"2017","journal-title":"Oxid. Med. Cell. Longev."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1013","DOI":"10.1016\/j.jaad.2012.02.009","article-title":"The Role of Antioxidants in Photoprotection: A Critical Review","volume":"67","author":"Chen","year":"2012","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1016\/j.jphotobiol.2006.02.012","article-title":"Photoprotective Properties of Prunella vulgaris and Rosmarinic Acid on Human Keratinocytes","volume":"84","author":"Psotova","year":"2006","journal-title":"J. Photochem. Photobiol. B Biol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"332","DOI":"10.1046\/j.1365-2133.1998.02447.x","article-title":"Topical Melatonin in Combination with Vitamins E and C Protects Skin from Ultraviolet-Induced Erythema: A Human Study In Vivo","volume":"139","author":"Dreher","year":"1998","journal-title":"Br. J. Dermatol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1016\/j.jphotobiol.2017.01.025","article-title":"Effect of Thai Banana (Musa AA group) in Reducing Accumulation of Oxidation End Products in UVB-Irradiated Mouse Skin","volume":"168","author":"Leerach","year":"2017","journal-title":"J. Photochem. Photobiol. B Biol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1016\/j.jphotobiol.2008.11.011","article-title":"Protective Effect of Fucoxanthin Isolated from Sargassum Siliquastrum on UV-B Induced Cell Damage","volume":"95","author":"Heo","year":"2009","journal-title":"J. Photochem. Photobiol. B Biol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"270","DOI":"10.4062\/biomolther.2013.030","article-title":"Fucoxanthin Protects Cultured Human Keratinocytes Against Oxidative Stress by Blocking free Radicals and Inhibiting Apoptosis","volume":"21","author":"Zheng","year":"2013","journal-title":"Biomol. Ther. (Seoul)"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1007\/s00403-009-0999-6","article-title":"Prunella Vulgaris Extract and Rosmarinic Acid Prevent UVB-Induced DNA Damage and Oxidative Stress in HaCaT Keratinocytes","volume":"302","year":"2010","journal-title":"Arch. Dermatol. Res."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"6103","DOI":"10.1038\/sj.onc.1204707","article-title":"G2 Phase Cell Cycle Arrest in Human Skin Following UV Irradiation","volume":"20","author":"Pavey","year":"2001","journal-title":"Oncogene"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/j.tox.2015.09.006","article-title":"Chlorpyrifos Induces NLRP3 Inflammasome and Pyroptosis\/Apoptosis Via Mitochondrial Oxidative Stress in Human Keratinocyte HaCaT Cells","volume":"338","author":"Jang","year":"2015","journal-title":"Toxicology"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"18384","DOI":"10.1073\/pnas.1209171109","article-title":"Tissue-Specific Opposing Functions of the Inflammasome Adaptor ASC in the Regulation of Epithelial Skin Carcinogenesis","volume":"109","author":"Drexler","year":"2012","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"271","DOI":"10.3389\/fimmu.2017.00271","article-title":"Inflammasomes in Inflammation-Induced Cancer","volume":"8","author":"Lin","year":"2017","journal-title":"Front. Immunol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1002\/jbt.21769","article-title":"Fucoxanthin Inhibits the Inflammation Response in Paw Edema Model Through Suppressing MAPKs, Akt, and NF\u03baB","volume":"30","author":"Choi","year":"2016","journal-title":"J. Biochem. Mol. Toxicol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1007\/s10753-013-9757-1","article-title":"First Evidence for the Anti-Inflammatory Activity of Fucoxanthin in High-Fat-Diet-Induced Obesity in Mice and the Antioxidant Functions in PC12 Cells","volume":"37","author":"Tan","year":"2014","journal-title":"Inflammation"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1054","DOI":"10.1002\/ptr.5093","article-title":"Effect of Fucoxanthin Alone and in Combination with D-Glucosamine Hydrochloride on Carrageenan\/Kaolin-Induced Experimental Arthritis in Rats","volume":"28","author":"Gong","year":"2014","journal-title":"Phyther. Res."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Rodr\u00edguez-Luna, A., \u00c1vila-Rom\u00e1n, J., Gonz\u00e1lez-Rodr\u00edguez, M.L., C\u00f3zar, M.J., Rabasco, A.M., Motilva, V., and Talero, E. (2018). Fucoxanthin-Containing Cream Prevents Epidermal Hyperplasia and UVB-Induced Skin Erythema in Mice. Mar. Drugs, 16.","DOI":"10.3390\/md16100378"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"366","DOI":"10.1038\/sj.bjp.0706728","article-title":"Rosmarinic Acid as a Downstream Inhibitor of IKK-Beta in TNF-Alpha-Induced Upregulation of CCL11 and CCR3","volume":"148","author":"Lee","year":"2006","journal-title":"Br. J. Pharmacol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1258\/ebm.2010.010252","article-title":"Effect of Perilla Frutescens Var. Acuta Kudo and Rosmarinic Acid on Allergic Inflammatory Reactions","volume":"236","author":"Oh","year":"2011","journal-title":"Exp. Biol. Med. (Maywood)"},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Jeong, H.J., Choi, Y., Kim, M.H., Kang, I.C., Lee, J.H., Park, C., Park, R., and Kim, H.M. (2011). Rosmarinic Acid, Active Component of Dansam-Eum Attenuates Ototoxicity of Cochlear Hair Cells Through Blockage of Caspase-1 Activity. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0018815"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"4214","DOI":"10.3390\/md12074214","article-title":"Fucoxanthin Enhances the Level of Reduced Glutathione Via the Nrf2-Mediated Pathway in Human Keratinocytes","volume":"12","author":"Zheng","year":"2014","journal-title":"Mar. Drugs"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"2728","DOI":"10.1007\/s11064-016-1989-7","article-title":"Fucoxanthin Activates Apoptosis Via Inhibition of PI3K\/Akt\/mTOR Pathway and Suppresses Invasion and Migration by Restriction of p38-MMP-2\/9 Pathway in Human Glioblastoma Cells","volume":"41","author":"Liu","year":"2016","journal-title":"Neurochem. Res."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"757","DOI":"10.1271\/bbb.110040","article-title":"Protective Effect of Fucoxanthin Against UVB-Induced Skin Photoaging in Hairless Mice","volume":"75","author":"Urikura","year":"2011","journal-title":"Biosci. Biotechnol. Biochem."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1137","DOI":"10.1111\/j.2042-7158.2010.01139.x","article-title":"Anti-Pigmentary Activity of Fucoxanthin and Its Influence on Skin mRNA Expression of Melanogenic Molecules","volume":"62","author":"Shimoda","year":"2010","journal-title":"J. Pharm. Pharmacol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/j.jphs.2016.08.004","article-title":"Protective and Therapeutic Effects of Fucoxanthin Against Sunburn Caused by UV Irradiation","volume":"132","author":"Matsui","year":"2016","journal-title":"J. Pharmacol. Sci."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1273","DOI":"10.1016\/j.phymed.2016.06.008","article-title":"Dietary Foeniculum Vulgare Mill Extract Attenuated UVB Irradiation-Induced Skin Photoaging by Activating of Nrf2 and Inhibiting MAPK Pathways","volume":"23","author":"Sun","year":"2016","journal-title":"Phytomedicine"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"336","DOI":"10.1111\/jcmm.12968","article-title":"Thymus Vulgaris Alleviates UVB Irradiation Induced Skin Damage Via Inhibition of MAPK\/AP-1 and Activation of Nrf2-ARE Antioxidant System","volume":"21","author":"Sun","year":"2016","journal-title":"J. Cell. Mol. Med."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1016\/j.taap.2017.01.008","article-title":"Rosmarinic Acid Counteracts Activation of Hepatic Stellate Cells Via Inhibiting the ROS-Dependent MMP-2 Activity: Involvement of Nrf2 Antioxidant System","volume":"318","author":"Lu","year":"2017","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1038\/bjc.1987.190","article-title":"A Study of Some Variables in a Tetrazolium Dye (MTT) Based Assay for Cell Growth and Chemosensitivity","volume":"56","author":"Twentyman","year":"1987","journal-title":"Br. J. Cancer"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"612","DOI":"10.1016\/S0891-5849(99)00107-0","article-title":"Quantifying Cellular Oxidative Stress by Dichlorofluorescein Assay Using Microplate Reader","volume":"27","author":"Wang","year":"1999","journal-title":"Free Radic. Biol. Med."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1016\/0003-2697(76)90527-3","article-title":"A Rapid and Sensitive Method for The Quantitation of Microgram Quantities of Protein Utilizing the Principle of Protein-Dye Binding","volume":"72","author":"Bradford","year":"1976","journal-title":"Anal. Biochem."}],"container-title":["Marine Drugs"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1660-3397\/17\/8\/451\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T13:12:01Z","timestamp":1760188321000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1660-3397\/17\/8\/451"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,8,1]]},"references-count":58,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2019,8]]}},"alternative-id":["md17080451"],"URL":"https:\/\/doi.org\/10.3390\/md17080451","relation":{},"ISSN":["1660-3397"],"issn-type":[{"value":"1660-3397","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,8,1]]}}}