{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T19:54:25Z","timestamp":1790884465783,"version":"4.1.0"},"reference-count":78,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Plants"],"abstract":"<jats:p>Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by persistent synovial inflammation, oxidative stress, and progressive joint destruction. Given the limitations and adverse effects of current therapies, medicinal plants represent a valuable source of novel anti-inflammatory agents. This study evaluated the phytochemical composition, antioxidant, immunomodulatory, and anti-arthritic activities of an ethanolic extract of Urtica urens (UUEE). LC-ESI-HRMS analysis identified forty metabolites, mainly hydroxycinnamic acid derivatives, flavonoids, terpenoid glycosides, and oxidized fatty acids. Antioxidant activity was assessed using DPPH, ABTS, and CUPRAC assays together with total phenolic and flavonoid contents. Anti-arthritic activity was investigated by inhibition of heat-induced bovine serum albumin denaturation, while cytotoxicity and genotoxicity were evaluated in HeLa and HaCaT cells. Immunomodulatory activity was assessed by analyzing IL-6 and IL-1\u03b2 expression in zymosan-stimulated HaCaT cells. Therapeutic efficacy was validated in a Freund\u2019s complete adjuvant-induced arthritis model in Wistar rats. UUEE showed strong antioxidant activity, concentration-dependent inhibition of protein denaturation, low cytotoxicity up to 100 \u03bcg\/mL, downregulation of pro-inflammatory cytokines, and significant in vivo anti-arthritic effects, reducing oxidative stress, histopathological damage, and arthritis severity while improving hematological and biochemical parameters. These findings support U. urens as a promising source of bioactive compounds for RA management.<\/jats:p>","DOI":"10.3390\/plants15193018","type":"journal-article","created":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T18:43:24Z","timestamp":1790880204000},"page":"3018","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Phytochemical Characterization and Integrated In Vitro Cellular Evaluation of Immunomodulatory, Cytotoxic, Genotoxic Activities and In Vivo Assessment of the Antioxidant and Anti-Arthritic Activities of Urtica urens L. Ethanolic Extract"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-4825-2528","authenticated-orcid":false,"given":"Hamza","family":"Kemchache","sequence":"first","affiliation":[{"name":"Laboratory of Applied Biochemistry, Faculty of Nature and Life Sciences, Ferhat Abbas University Setif -1-, Setif 19000, Algeria"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"methodology","vocabulary":"credit"},{"role":"software","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1601-3661","authenticated-orcid":false,"given":"Hanane","family":"Khither","sequence":"additional","affiliation":[{"name":"Laboratory of Applied Biochemistry, Faculty of Nature and Life Sciences, Ferhat Abbas University Setif -1-, Setif 19000, Algeria"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"},{"role":"project-administration","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-2905-1171","authenticated-orcid":false,"given":"Khalil","family":"Kaouane","sequence":"additional","affiliation":[{"name":"Laboratory of Applied Biochemistry, Faculty of Nature and Life Sciences, Ferhat Abbas University Setif -1-, Setif 19000, Algeria"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"methodology","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"}]},{"given":"Soraya","family":"Madoui","sequence":"additional","affiliation":[{"name":"Laboratory of Applied Biochemistry, Faculty of Nature and Life Sciences, Ferhat Abbas University Setif -1-, Setif 19000, Algeria"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"},{"role":"project-administration","vocabulary":"credit"}]},{"given":"Amina","family":"Safsaf","sequence":"additional","affiliation":[{"name":"Pathology Laboratory, Setif University Hospital, Setif 19000, Algeria"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"data-curation","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"}]},{"given":"Khalida","family":"Hammoudi","sequence":"additional","affiliation":[{"name":"Faculty of Medecine, Ferhat Abbas University Setif -1-, Setif 19000, Algeria"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"investigation","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"}]},{"given":"Stefania","family":"Ponticelli","sequence":"additional","affiliation":[{"name":"Department of Biology, University of Naples Federico II, Via Cinthia 4, 80126 Napoli, Italy"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"methodology","vocabulary":"credit"},{"role":"software","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-5834-9123","authenticated-orcid":false,"given":"Martina","family":"Dentato","sequence":"additional","affiliation":[{"name":"Department of Biology, University of Naples Federico II, Via Cinthia 4, 80126 Napoli, Italy"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"methodology","vocabulary":"credit"},{"role":"software","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5641-3977","authenticated-orcid":false,"given":"Alessia","family":"Postiglione","sequence":"additional","affiliation":[{"name":"Department of Biology, University of Naples Federico II, Via Cinthia 4, 80126 Napoli, Italy"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"software","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9176-8044","authenticated-orcid":false,"given":"Daniela","family":"Rigano","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, School of Medicine and Surgery, University of Naples Federico II, Via Domenico Montesano 49, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"methodology","vocabulary":"credit"},{"role":"software","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"}]},{"given":"Carmina","family":"Sirignano","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, School of Medicine and Surgery, University of Naples Federico II, Via Domenico Montesano 49, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"methodology","vocabulary":"credit"},{"role":"software","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4656-320X","authenticated-orcid":false,"given":"Viviana","family":"Maresca","sequence":"additional","affiliation":[{"name":"Department of Life Sciences, Health and Health Professions, University of Rome \u201cLink Campus\u201d, 00165 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4612-4642","authenticated-orcid":false,"given":"Chawki","family":"Bensouici","sequence":"additional","affiliation":[{"name":"National Center for Biotechnology Research, Ali Mendjli, Nouvelle Ville UV 03, Constantine 25011, Algeria"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"methodology","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]}],"member":"1968","published-online":{"date-parts":[[2026,10,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Li, W., Qian, P., Guo, Y., Gu, L., Jurat, J., Bai, Y., and Zhang, D. (2021). Myrtenal and \u03b2-Caryophyllene Oxide Screened from Liquidambaris Fructus Suppress NLRP3 Inflammasome Components in Rheumatoid Arthritis. BMC Complement. Med. Ther., 21.","DOI":"10.1186\/s12906-021-03410-2"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1","DOI":"10.2306\/scienceasia1513-1874.2025.008","article-title":"Anti-Inflammatory Effect of Rhamnella gilgitica Mansf. et Melch on Complete Freund?S Adjuvant Induced-Arthritis Mice and Lipopolysaccharide (LPS)-Treated RAW264.7 Cells by Mediating the MAPK Signaling Pathway","volume":"51","author":"Sambu","year":"2025","journal-title":"ScienceAsia"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1007\/s40744-017-0073-3","article-title":"Treatment with Biologicals in Rheumatoid Arthritis: An Overview","volume":"4","author":"Rein","year":"2017","journal-title":"Rheumatol. Ther."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"8084","DOI":"10.1002\/fsn3.4418","article-title":"EXPRESSION OF CONCERN: Diospyros kaki Fruit Extract Produces Antiarthritic and Antinociceptive Effects in Rats with Complete Freund\u2019s Adjuvant-induced Arthritis","volume":"12","author":"Forouzanfar","year":"2024","journal-title":"Food Sci. Nutr."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1007\/s11010-022-04492-3","article-title":"Rheumatoid Arthritis: Advances in Treatment Strategies","volume":"478","author":"Prasad","year":"2023","journal-title":"Mol. Cell. Biochem."},{"key":"ref_6","first-page":"94","article-title":"Effects of Solanum nigrum on Liver Enzymes and Hematological Profile in Complete Freund\u2019s Adjuvant-Induced Arthritic Rats","volume":"14","author":"Rasheed","year":"2025","journal-title":"Pak. J. Med. Dent."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Manful, C.F., Fordjour, E., Ikumoinein, E., Abbey, L., and Thomas, R. (2025). Therapeutic strategies targeting oxidative stress and inflammation: A narrative review. BioChem, 5.","DOI":"10.3390\/biochem5040035"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"574600","DOI":"10.2147\/IJN.S574600","article-title":"Therapeutic Nanozymes in Rheumatoid Arthritis Treatment Through Disease Stage-Oriented Strategies","volume":"21","author":"Zhou","year":"2026","journal-title":"Int. J. Nanomed."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1038\/s41413-018-0016-9","article-title":"Rheumatoid arthritis: Pathological mechanisms and modern pharmacologic therapies","volume":"6","author":"Guo","year":"2018","journal-title":"Bone Res."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Radu, A.-F., and Bungau, S.G. (2021). Management of Rheumatoid Arthritis: An Overview. Cells, 10.","DOI":"10.3390\/cells10112857"},{"key":"ref_11","first-page":"647","article-title":"Bioactive Ingredients and Anti-Influenza (H5N1), Anticancer, and Antioxidant Properties of Urtica urens L.","volume":"13","author":"Gaafar","year":"2020","journal-title":"J. Biol. Sci."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Kregiel, D., Pawlikowska, E., and Antolak, H. (2018). Urtica Spp.: Ordinary Plants with Extraordinary Properties. Molecules, 23.","DOI":"10.3390\/molecules23071664"},{"key":"ref_13","first-page":"121","article-title":"Phytochemical Analysis and Antioxidant Properties of Urtica urens","volume":"9","author":"Paul","year":"2021","journal-title":"J. Med. Plants Stud."},{"key":"ref_14","first-page":"9274","article-title":"Phytochemical Analyses and Antioxidant Activity of a Traditional Food Source: Dwarf Nettle (Urtica urens L.)","volume":"28","author":"Bagdatli","year":"2019","journal-title":"Fresenius Environ. Bull."},{"key":"ref_15","first-page":"14","article-title":"Phytochemical Analysis, Antioxidant and In Vitro Anti-Inflammatory Activity of Leaves Ethanol Extracts from a Moroccan Plant Urtica urens L.","volume":"14","author":"Rahim","year":"2024","journal-title":"Lett. Appl. NanoBioSci."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1807","DOI":"10.1002\/ptr.3188","article-title":"Evaluation of Antinociceptive, Antinflammatory Activities and Phytochemical Analysis of Aerial Parts of Urtica urens L.","volume":"24","author":"Marrassini","year":"2010","journal-title":"Phytother. Res."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"867","DOI":"10.1146\/annurev-arplant-071720-114836","article-title":"Next-Generation Mass Spectrometry Metabolomics Revives the Functional Analysis of Plant Metabolic Diversity","volume":"72","author":"Li","year":"2021","journal-title":"Annu. Rev. Plant Biol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1111\/j.1365-313X.2012.04902.x","article-title":"High-Resolution Plant Metabolomics: From Mass Spectral Features to Metabolites and from Whole-Cell Analysis to Subcellular Metabolite Distributions","volume":"70","author":"Kueger","year":"2012","journal-title":"Plant J."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1016\/j.foodchem.2013.07.097","article-title":"Quantitative Determination of Plant Phenolics in Urtica dioica Extracts by High-Performance Liquid Chromatography Coupled with Tandem Mass Spectrometric Detection","volume":"143","author":"Bekvalac","year":"2014","journal-title":"Food Chem."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Ekor, M. (2014). The Growing Use of Herbal Medicines: Issues Relating to Adverse Reactions and Challenges in Monitoring Safety. Front. Pharmacol., 4.","DOI":"10.3389\/fphar.2013.00177"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1055\/s-2006-960190","article-title":"Caffeic Acid Esters from Urtica dioica and Urtica urens","volume":"57","author":"Budzianowski","year":"1991","journal-title":"Planta Med."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"472","DOI":"10.1016\/j.jpba.2008.04.014","article-title":"Hydroxycinnamic Acid Derivatives Occurring in Cichorium endivia Vegetables","volume":"48","author":"Papetti","year":"2008","journal-title":"J. Pharm. Biomed. Anal."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1247","DOI":"10.1002\/bmc.2686","article-title":"Determination of the Esculetin Contents of Medicinal Plants by Liquid Chromatography\u2013Tandem Mass Spectrometry","volume":"26","author":"Yun","year":"2012","journal-title":"Biomed. Chromatogr."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1016\/j.phytochem.2013.09.016","article-title":"Phytochemical, Phylogenetic, and Anti-Inflammatory Evaluation of 43 Urtica Accessions (Stinging Nettle) Based on UPLC\u2013Q-TOF-MS Metabolomic Profiles","volume":"96","author":"Farag","year":"2013","journal-title":"Phytochemistry"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"680","DOI":"10.1007\/s10600-023-04085-6","article-title":"A New Geranyl Phenylacetate Glycoside from the Twigs of Aphanamixis polystachya","volume":"59","author":"Zhao","year":"2023","journal-title":"Chem. Nat. Compd."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"3432","DOI":"10.1039\/D4MA00007B","article-title":"Unveiling the Functional Components and Anti-Alzheimer\u2019s Activity of Koelreuteria elegans (Seem.) A.C. Sm. Using UHPLC-MS\/MS and Molecular Networking","volume":"5","author":"Demerdash","year":"2024","journal-title":"Mater. Adv."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1007\/s12298-024-01420-1","article-title":"Lipid Peroxidation and Stress-Induced Signalling Molecules in Systemic Resistance Mediated by Azelaic Acid\/AZELAIC ACID INDUCED1: Signal Initiation and Propagation","volume":"30","author":"Reddy","year":"2024","journal-title":"Physiol. Mol. Biol. Plants"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"3747","DOI":"10.1007\/s11033-021-06344-7","article-title":"Signals in Systemic Acquired Resistance of Plants against Microbial Pathogens","volume":"48","author":"Gao","year":"2021","journal-title":"Mol. Biol. Rep."},{"key":"ref_29","first-page":"690596","article-title":"Anti-Inflammatory and Antiarthritic Activity of Anthraquinone Derivatives in Rodents","volume":"2014","author":"Kshirsagar","year":"2014","journal-title":"Int. J. Inflamm."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"e070856","DOI":"10.1136\/bmj-2022-070856","article-title":"Therapeutic Advances in Rheumatoid Arthritis","volume":"384","author":"Brown","year":"2024","journal-title":"BMJ"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"157285","DOI":"10.1016\/j.phymed.2025.157285","article-title":"Phytotherapy as an Adjunct to the Treatment of Rheumatoid Arthritis-a Systematic Review of Clinical Trials","volume":"148","author":"Piekarz","year":"2025","journal-title":"Phytomedicine"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"518","DOI":"10.1016\/j.biopha.2017.10.150","article-title":"Chemoprotective Role of Ethanol Extract of Urtica urens L. against the Toxicity of Imidacloprid on Endocrine Disruption and Ovarian Morphometric in Female Rats, GC\/MS Analysis","volume":"97","author":"Mzid","year":"2018","journal-title":"Biomed. Pharmacother."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"232","DOI":"10.5897\/JMPR2019.6880","article-title":"DPPH Radical Scavenging Activity of Extracts from Urtica urens (Urticaceae)","volume":"14","author":"Manoharan","year":"2020","journal-title":"J. Med. Plants Res."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"2500","DOI":"10.1002\/fsn3.3308","article-title":"Phytobioactive Compounds as Therapeutic Agents for Human Diseases: A Review","volume":"11","author":"Riaz","year":"2023","journal-title":"Food Sci. Nutr."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"775","DOI":"10.1080\/13880209.2016.1275025","article-title":"Antioxidant and Antimicrobial Activities of Ethanol and Aqueous Extracts from Urtica urens","volume":"55","author":"Mzid","year":"2017","journal-title":"Pharm. Biol."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Lin, H.-J.L., Parkinson, D.H., Holman, J.C., Thompson, W.C., Anderson, C.N.K., Hadfield, M., Ames, S., Zuniga Pina, N.R., Bowden, J.N., and Quinn, C. (2023). Modification of the Structural Stability of Human Serum Albumin in Rheumatoid Arthritis. PLoS ONE, 18.","DOI":"10.1371\/journal.pone.0271008"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1038\/s41584-023-00966-w","article-title":"Matrix Metalloproteinases in Arthritis: Towards Precision Medicine","volume":"19","author":"Grillet","year":"2023","journal-title":"Nat. Rev. Rheumatol."},{"key":"ref_38","first-page":"271","article-title":"The Potential of Stinging Nettle (Urtica dioica L.) as a Functional Food and Its Use in Agriculture and Healthcare","volume":"4","author":"Papazoglou","year":"2015","journal-title":"Plants"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1016\/j.jep.2003.09.028","article-title":"Antioxidant, Antimicrobial, Antiulcer and Analgesic Activities of Nettle (Urtica dioica L.)","volume":"90","author":"Oktay","year":"2004","journal-title":"J. Ethnopharmacol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1146\/annurev-food-052720-100326","article-title":"Current Understanding of Modes of Action of Multicomponent Bioactive Phytochemicals: Potential for Nutraceuticals and Antimicrobials","volume":"13","author":"Wink","year":"2022","journal-title":"Annu. Rev. Food Sci. Technol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"869","DOI":"10.1039\/C9NP00011A","article-title":"Synergy and Antagonism in Natural Product Extracts: When 1 + 1 Does Not Equal 2","volume":"36","author":"Caesar","year":"2019","journal-title":"Nat. Prod. Rep."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1038\/nri2094","article-title":"Cytokines in the Pathogenesis of Rheumatoid Arthritis","volume":"7","author":"McInnes","year":"2007","journal-title":"Nat. Rev. Immunol."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Al-Khayri, J.M., Sahana, G.R., Nagella, P., Joseph, B.V., Alessa, F.M., and Al-Mssallem, M.Q. (2022). Flavonoids as Potential Anti-Inflammatory Molecules: A Review. Molecules, 27.","DOI":"10.3390\/molecules27092901"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"7435621","DOI":"10.1155\/2017\/7435621","article-title":"HaCaT Cells as a Reliable In Vitro Differentiation Model to Dissect the Inflammatory\/Repair Response of Human Keratinocytes","volume":"2017","author":"Colombo","year":"2017","journal-title":"Mediat. Inflamm."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Azqueta, A., Slyskova, J., Langie, S.A.S., O\u2019Neill Gaiv\u00e3o, I., and Collins, A. (2014). Comet Assay to Measure DNA Repair: Approach and Applications. Front. Genet., 5.","DOI":"10.3389\/fgene.2014.00288"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"3803","DOI":"10.1007\/s00204-021-03164-3","article-title":"Cell Survival after DNA Damage in the Comet Assay","volume":"95","author":"Bankoglu","year":"2021","journal-title":"Arch. Toxicol."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Azqueta, A., and Collins, A. (2016). Polyphenols and DNA Damage: A Mixed Blessing. Nutrients, 8.","DOI":"10.3390\/nu8120785"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1075","DOI":"10.1055\/s-0030-1249961","article-title":"Modulation of Apoptosis by Natural Products for Cancer Therapy","volume":"76","author":"Fulda","year":"2010","journal-title":"Planta Med."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"09731296251326642","DOI":"10.1177\/09731296251326642","article-title":"Anti-Arthritic Activity of Citral Against Complete Freund\u2019s Adjuvant-Induced Arthritis in Rats Through NF-\u03baB Signaling Pathway","volume":"2","author":"Kong","year":"2025","journal-title":"Pharmacogn. Mag."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Noh, A.S.M., Chuan, T.D., Khir, N.A.M., Zin, A.A.M., Ghazali, A.K., Long, I., Ab Aziz, C.B., and Ismail, C.A.N. (2021). Effects of Different Doses of Complete Freund\u2019s Adjuvant on Nociceptive Behaviour and Inflammatory Parameters in Polyarthritic Rat Model Mimicking Rheumatoid Arthritis. PLoS ONE, 16.","DOI":"10.1371\/journal.pone.0260423"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1016\/j.jep.2019.03.019","article-title":"Ribes orientale: A Novel Therapeutic Approach Targeting Rheumatoid Arthritis with Reference to pro-Inflammatory Cytokines, Inflammatory Enzymes and Anti-Inflammatory Cytokines","volume":"237","author":"Uttra","year":"2019","journal-title":"J. Ethnopharmacol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"257","DOI":"10.3831\/KPI.2023.26.3.257","article-title":"Antiarthritic Activity and Inflammatory Mediators Modulation Effect of Traditional Ajmodadi Churna on Arthritis Experimental Model","volume":"26","author":"Sharma","year":"2023","journal-title":"J. Pharmacopunct."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1016\/j.jep.2014.05.023","article-title":"Anti-Arthritic Activity of Xanthium strumarium L. Extract on Complete Freund\u05f3s Adjuvant Induced Arthritis in Rats","volume":"155","author":"Lin","year":"2014","journal-title":"J. Ethnopharmacol."},{"key":"ref_54","first-page":"177","article-title":"Effect of Celastrus paniculatus Willd. Seed on Adjuvant Induced Arthritis in Rats","volume":"3","author":"Patil","year":"2007","journal-title":"Pharmacogn. Mag."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1016\/j.freeradbiomed.2012.12.003","article-title":"Oxidative State of the Liver of Rats with Adjuvant-Induced Arthritis","volume":"58","author":"Comar","year":"2013","journal-title":"Free Radic. Biol. Med."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1186\/s43094-025-00807-5","article-title":"Assessment of the Possible Ameliorative Effects of Beta-Caryophyllene Oxide Either Alone or in Combination with Methotrexate in Complete Freund\u2019s Adjuvant-Induced Arthritis in Wistar Rats","volume":"11","author":"Saleem","year":"2025","journal-title":"Futur. J. Pharm. Sci."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1038\/nrrheum.2016.166","article-title":"Interleukin-1 Function and Role in Rheumatic Disease","volume":"12","author":"Schett","year":"2016","journal-title":"Nat. Rev. Rheumatol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1016\/j.biomag.2014.04.007","article-title":"Anti-Arthritic Activity of Methanol Extract of Cyathocline purpurea (Whole Plant) in Freund\u2019s Complete Adjuvant-Induced Arthritis in Rats","volume":"4","author":"Bihani","year":"2014","journal-title":"Biomed. Aging Pathol."},{"key":"ref_59","first-page":"332","article-title":"Rutin Attenuates Complete Freund\u2019s Adjuvant-Induced Inflammatory Pain in Rats","volume":"28","author":"Forouzanfar","year":"2025","journal-title":"Iran. J. Basic Med. Sci."},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Vairetti, M., Di Pasqua, L.G., Cagna, M., Richelmi, P., Ferrigno, A., and Berardo, C. (2021). Changes in Glutathione Content in Liver Diseases: An Update. Antioxidants, 10.","DOI":"10.3390\/antiox10030364"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"9613090","DOI":"10.1155\/2019\/9613090","article-title":"Role of Catalase in Oxidative Stress- and Age-Associated Degenerative Diseases","volume":"2019","author":"Nandi","year":"2019","journal-title":"Oxidative Med. Cell. Longev."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"129","DOI":"10.21608\/mjmu.2021.98112.1042","article-title":"Histological Study of Hyaline Articular Cartilage Changes in a Rat Model of Complete Freund\u2019s Adjuvant-Induced Arthritis of the Knee Joint","volume":"50","author":"Hamed","year":"2021","journal-title":"Mansoura Med. J."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"27","DOI":"10.4103\/0976-0105.177703","article-title":"A Simple Practice Guide for Dose Conversion between Animals and Human","volume":"7","author":"Nair","year":"2016","journal-title":"J. Basic Clin. Pharm."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"374","DOI":"10.1021\/jf072510j","article-title":"Microwave-Assisted Efficient Extraction of Different Parts of Hippophae rhamnoides for the Comparative Evaluation of Antioxidant Activity and Quantification of Its Phenolic Constituents by Reverse-Phase High-Performance Liquid Chromatography (RP-HPLC)","volume":"56","author":"Sharma","year":"2008","journal-title":"J. Agric. Food Chem."},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Kaouane, K., Madoui, S., Kemchache, H., Khither, H., Safsaf, A., Hammoudi, K., Ponticelli, S., Dentato, M., Postiglione, A., and Bensouici, C. (2026). Phytochemical Characterization and Evaluation of Antioxidant, Anti-Inflammatory, Cytotoxic, Genotoxic, and Anti-Arthritic Activities of Atriplex halimus Aqueous Leaf Extract. Plants, 15.","DOI":"10.3390\/plants15142164"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1199","DOI":"10.1038\/1811199a0","article-title":"Antioxidant Determinations by the Use of a Stable Free Radical","volume":"181","author":"Blois","year":"1958","journal-title":"Nature"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1231","DOI":"10.1016\/S0891-5849(98)00315-3","article-title":"Antioxidant Activity Applying an Improved ABTS Radical Cation Decolorization Assay","volume":"26","author":"Re","year":"1999","journal-title":"Free Radic. Biol. Med."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"7970","DOI":"10.1021\/jf048741x","article-title":"Novel Total Antioxidant Capacity Index for Dietary Polyphenols and Vitamins C and E, Using Their Cupric Ion Reducing Capability in the Presence of Neocuproine: CUPRAC Method","volume":"52","author":"Apak","year":"2004","journal-title":"J. Agric. Food Chem."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"771","DOI":"10.1016\/j.foodchem.2006.06.022","article-title":"Evaluation of Antioxidant Capacity and Total Phenolic Content of Different Fractions of Selected Microalgae","volume":"102","author":"Li","year":"2007","journal-title":"Food Chem."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"657","DOI":"10.1007\/s11094-022-02691-2","article-title":"Development of Quantitative Determination Methods for Total Flavonoids in Tagetes patula L. Herbs","volume":"56","author":"Kurkina","year":"2022","journal-title":"Pharm. Chem. J."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1016\/0014-4827(88)90265-0","article-title":"A Simple Technique for Quantitation of Low Levels of DNA Damage in Individual Cells","volume":"175","author":"Singh","year":"1988","journal-title":"Exp. Cell Res."},{"key":"ref_72","doi-asserted-by":"crossref","unstructured":"Dentato, M., Porrello, A., De Marino, E., Ponticelli, S., Postiglione, A., Pollice, A., Bruno, M., Badalamenti, N., Bazan, G., and Maresca, V. (2025). Analytical Determination of the Lipid Fraction of Nigella sativa Fatty Oil by GC and NMR Analysis and Evaluation of Its Cytotoxic and Antioxidant Activity. Molecules, 30.","DOI":"10.3390\/molecules30214300"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"388","DOI":"10.22270\/jddt.v8i5-s.1922","article-title":"Anti-arthritic evaluation of different extracts of Boerhaavia diffusa Linn. in FCA induced arthritis in rats","volume":"8","author":"Parmar","year":"2018","journal-title":"J. Drug Deliv. Ther."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1146\/annurev.nu.09.070189.001443","article-title":"Nutritional and Metabolic Aspects of Glutathione","volume":"9","author":"Beutler","year":"1989","journal-title":"Annu. Rev. Nutr."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1016\/0003-2697(79)90738-3","article-title":"Assay for Lipid Peroxides in Animal Tissues by Thiobarbituric Acid Reaction","volume":"95","author":"Ohkawa","year":"1979","journal-title":"Anal. Biochem."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1016\/S0076-6879(84)05016-3","article-title":"Catalase in Vitro","volume":"Volume 105","author":"Aebi","year":"1984","journal-title":"Methods in Enzymology"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"590","DOI":"10.3109\/08923973.2011.641971","article-title":"Mucosal Intestinal Alteration in Experimental Colitis Correlates with Nitric Oxide Production by Peritoneal Macrophages: Effect of Probiotics and Prebiotics","volume":"34","author":"Abdelouhab","year":"2012","journal-title":"Immunopharmacol. Immunotoxicol."},{"key":"ref_78","unstructured":"Bancroft, J.D., and Gamble, M. (2008). Theory and Practice of Histological Techniques, Elsevier Health Sciences."}],"container-title":["Plants"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2223-7747\/15\/19\/3018\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T18:58:17Z","timestamp":1790881097000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2223-7747\/15\/19\/3018"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10,1]]},"references-count":78,"journal-issue":{"issue":"19","published-online":{"date-parts":[[2026,10]]}},"alternative-id":["plants15193018"],"URL":"https:\/\/doi.org\/10.3390\/plants15193018","relation":{},"ISSN":["2223-7747"],"issn-type":[{"value":"2223-7747","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10,1]]}}}