{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T10:08:25Z","timestamp":1789639705009,"version":"4.0.0"},"reference-count":84,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2026,3,15]],"date-time":"2026-03-15T00:00:00Z","timestamp":1773532800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Plant-based remedies have been employed since ancient times to manage and prevent a wide range of diseases. Background: Their bioactive constituents provide natural alternatives to synthetic anti-inflammatory drugs, often with reduced toxicity and multiple biological benefits. Mandragora autumnalis, a medicinal plant rich in secondary metabolites, has not been extensively investigated for its anti-inflammatory properties. Methods: The anti-inflammatory activity of Mandragora autumnalis ethanolic extract (MAE) was evaluated using in vitro biochemical assays, including heat-induced protein denaturation (casein and bovine serum albumin) and red blood cell membrane stabilization. Cellular anti-inflammatory effects were assessed in LPS-stimulated RAW 264.7 macrophages by measuring nitric oxide production, pro-inflammatory cytokine levels, macrophage migration, gene and protein expression of inflammatory mediators, and the activation status of NF-\u03baB, STAT3, and MAPK signaling pathways. Results: Preliminary screening revealed that MAE effectively inhibited heat-induced protein denaturation (casein and bovine serum albumin) and heat-induced red blood cell (RBC) hemolysis, indicating strong protein- and membrane-stabilizing properties associated with anti-inflammatory activity. In lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages, MAE markedly suppressed the inflammatory response by downregulating the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), leading to a significant reduction in nitric oxide (NO) production and pro-inflammatory cytokines, including tumor necrosis factor-\u03b1 (TNF-\u03b1) and interleukin-6 (IL-6). Furthermore, MAE inhibited macrophage migration and attenuated key inflammatory signaling pathways, notably nuclear factor kappa B (NF-\u03baB), signal transducer and activator of transcription 3 (STAT3), and mitogen-activated protein kinases (MAPKs). Molecular docking analysis was conducted to explore the potential interactions between the most abundant chemical compounds and key proteins involved in inflammatory signaling pathways, including ERK and iNOS. Conclusions: Overall, these results indicate that MAE exhibits strong anti-inflammatory activity by stabilizing proteins, protecting cellular membranes, and inhibiting key inflammatory mediators and signaling pathways. These findings highlight its potential as a natural therapeutic candidate for the prevention and management of chronic inflammation-related disorders, such as arthritis, cardiovascular diseases, and cancer. However, further mechanistic investigations and in vivo studies are required to confirm its therapeutic potential and clinical relevance.<\/jats:p>","DOI":"10.3390\/ph19030483","type":"journal-article","created":{"date-parts":[[2026,3,16]],"date-time":"2026-03-16T11:13:14Z","timestamp":1773659594000},"page":"483","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Anti-Inflammatory Activity of Mandragora autumnalis Ethanolic Extract: In Vitro and Cellular Mechanistic Insights"],"prefix":"10.3390","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4489-6606","authenticated-orcid":false,"given":"Ghosoon","family":"Albahri","sequence":"first","affiliation":[{"name":"Faculty of Arts and Sciences, American University of Beirut, Beirut 1107, Lebanon"},{"name":"Doctoral School of Science and Technology-Platform of Research and Analysis in Environmental Sciences (EDST-PRASE), Beirut 1107, Lebanon"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heba","family":"Hellany","sequence":"additional","affiliation":[{"name":"Faculty of Arts and Sciences, American University of Beirut, Beirut 1107, Lebanon"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adnan","family":"Badran","sequence":"additional","affiliation":[{"name":"Department of Biology, University of Jordan, Amman 11942, Jordan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9517-071X","authenticated-orcid":false,"given":"Rami","family":"Abdel-Rahem","sequence":"additional","affiliation":[{"name":"Department of Chemistry, University of Petra, Amman 11196, Jordan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mayyas","family":"Al-Remawi","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy & Medical Sciences, University of Petra, Amman 19328, Jordan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamad","family":"Alame","sequence":"additional","affiliation":[{"name":"Doctoral School of Science and Technology-Platform of Research and Analysis in Environmental Sciences (EDST-PRASE), Beirut 1107, Lebanon"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4984-8531","authenticated-orcid":false,"given":"Akram","family":"Hijazi","sequence":"additional","affiliation":[{"name":"Doctoral School of Science and Technology-Platform of Research and Analysis in Environmental Sciences (EDST-PRASE), Beirut 1107, Lebanon"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2913-2846","authenticated-orcid":false,"given":"Mikhael","family":"Bechelany","sequence":"additional","affiliation":[{"name":"Institut Europ\u00e9en des Membranes, IEM, UMR-5635, University Montpellier, ENSCM, CNRS, Place Eugene Bataillon, 34095 Montpellier, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5632-1175","authenticated-orcid":false,"given":"Elias","family":"Baydoun","sequence":"additional","affiliation":[{"name":"Faculty of Arts and Sciences, American University of Beirut, Beirut 1107, Lebanon"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"7204","DOI":"10.18632\/oncotarget.23208","article-title":"Inflammatory Responses and Inflammation-Associated Diseases in Organs","volume":"9","author":"Chen","year":"2018","journal-title":"Oncotarget"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"428","DOI":"10.1038\/nature07201","article-title":"Origin and Physiological Roles of Inflammation","volume":"454","author":"Medzhitov","year":"2008","journal-title":"Nature"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"805","DOI":"10.1016\/j.cell.2010.01.022","article-title":"Pattern Recognition Receptors and Inflammation","volume":"140","author":"Takeuchi","year":"2010","journal-title":"Cell"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"871","DOI":"10.1016\/j.cell.2010.02.029","article-title":"Nonresolving Inflammation","volume":"140","author":"Nathan","year":"2010","journal-title":"Cell"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1070","DOI":"10.1126\/science.abi5200","article-title":"The Spectrum of Inflammatory Responses","volume":"374","author":"Medzhitov","year":"2021","journal-title":"Science"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"901","DOI":"10.1159\/000452591","article-title":"Triptolide Attenuates Inflammatory Response in Membranous Glomerulo-Nephritis Rat via Downregulation of NF-\u03baB Signaling Pathway","volume":"41","author":"Zhou","year":"2016","journal-title":"Kidney Blood Press. Res."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"115764","DOI":"10.1016\/j.biopha.2023.115764","article-title":"Biochemical Aspects of the Inflammatory Process: A Narrative Review","volume":"168","author":"Soares","year":"2023","journal-title":"Biomed. Pharmacother."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"e127925","DOI":"10.1172\/jci.insight.127925","article-title":"Damage- and Pathogen-Associated Molecular Patterns Play Differential Roles in Late Mortality after Critical Illness","volume":"4","author":"Eppensteiner","year":"2019","journal-title":"JCI Insight"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1128\/CMR.00046-08","article-title":"Pathogen Recognition and Inflammatory Signaling in Innate Immune Defenses","volume":"22","author":"Mogensen","year":"2009","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Nunes, C.D.R., Barreto Arantes, M., Menezes De Faria Pereira, S., Leandro Da Cruz, L., De Souza Passos, M., Pereira De Moraes, L., Vieira, I.J.C., and Barros De Oliveira, D. (2020). Plants as Sources of Anti-Inflammatory Agents. Molecules, 25.","DOI":"10.3390\/molecules25163726"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Kciuk, M., Garg, A., Rohilla, M., Chaudhary, R., Dhankhar, S., Dhiman, S., Bansal, S., Saini, M., Singh, T.G., and Chauhan, S. (2024). Therapeutic Potential of Plant-Derived Compounds and Plant Extracts in Rheumatoid Arthritis\u2014Comprehensive Review. Antioxidants, 13.","DOI":"10.3390\/antiox13070775"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Nakadate, K., Ito, N., Kawakami, K., and Yamazaki, N. (2025). Anti-Inflammatory Actions of Plant-Derived Compounds and Prevention of Chronic Diseases: From Molecular Mechanisms to Applications. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms26115206"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"W\u00f3jcik-Borowska, K., W\u00f3jciak, W., \u017buk, M., Luchowski, P., Skalska-Kami\u0144ska, A., Pacu\u0142a, W., Sowa, I., and W\u00f3jciak, M. (2025). Oxidative Stress Protection and Anti-Inflammatory Activity of Polyphenolic Fraction from Urtica Dioica: In Vitro Study Using Human Skin Cells. Molecules, 30.","DOI":"10.3390\/molecules30122515"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1038\/s41392-021-00658-5","article-title":"Inflammation and Tumor Progression: Signaling Pathways and Targeted Intervention","volume":"6","author":"Zhao","year":"2021","journal-title":"Sig. Transduct. Target. Ther."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Albahri, G., Badran, A., Hellany, H., Baydoun, S., Abdallah, R., Alame, M., Hijazi, A., Maresca, M., and Baydoun, E. (2025). Mandragora Autumnalis: Phytochemical Composition, Antioxidant and Anti-Cancerous Bioactivities on Triple-Negative Breast Cancer Cells. Int. J. Mol. Sci., 26.","DOI":"10.20944\/preprints202508.0372.v1"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Albahri, G., Badran, A., Hellany, H., Kafrouny, N., El Kurdi, R., Alame, M., Hijazi, A., Maresca, M., Patra, D., and Baydoun, E. (2025). Green Synthesis of Gold Nanoparticles Using Mandragora Autumnalis: Characterization and Evaluation of Its Antioxidant and Anticancer Bioactivities. Pharmaceuticals, 18.","DOI":"10.20944\/preprints202508.0275.v1"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1007\/BF02976483","article-title":"Inhibition of Heat-Induced Denaturation of Albumin by Nonsteroidal Antiinflammatory Drugs (NSAIDs): Pharmacological Implications","volume":"24","author":"Saso","year":"2001","journal-title":"Arch. Pharm. Res."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Casta\u00f1eda-Corral, G., Cedillo-Cortezano, M., and Petricevich, V.L. (2025). Parallel In Vitro and In Silico Studies of the Anti-Inflammatory Activity of Bioactive Compounds Found in Different Ethanolic Extracts of Bracts from B. x Buttiana (Var. Rose): A Comparative Analysis. Pharmaceuticals, 18.","DOI":"10.3390\/ph18060821"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1159\/000342229","article-title":"Red Blood Cell Clearance in Inflammation","volume":"39","author":"Straat","year":"2012","journal-title":"Transfus. Med. Hemother."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Al-Maharik, N., Jaradat, N., Bassalat, N., Hawash, M., and Zaid, H. (2022). Isolation, Identification and Pharmacological Effects of Mandragora Autumnalis Fruit Flavonoids Fraction. Molecules, 27.","DOI":"10.3390\/molecules27031046"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Albahri, G., Badran, A., Baki, Z.A., Alame, M., Hijazi, A., Daou, A., Mesmar, J.E., and Baydoun, E. (2025). Mandragora Autumnalis Distribution, Phytochemical Characteristics, and Pharmacological Bioactivities. Pharmaceuticals, 18.","DOI":"10.3390\/ph18030328"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"4952221","DOI":"10.1155\/2022\/4952221","article-title":"Medicinal Plants of Solanum Species: The Promising Sources of Phyto-Insecticidal Compounds","volume":"2022","author":"Chidambaram","year":"2022","journal-title":"J. Trop. Med."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"2619","DOI":"10.1172\/JCI124615","article-title":"The Role of Macrophages in the Resolution of Inflammation","volume":"129","author":"Watanabe","year":"2019","journal-title":"J. Clin. Investig."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"26362","DOI":"10.1038\/s41598-025-07273-2","article-title":"Ziziphus Nummularia Extract Attenuates Inflammatory Markers in RAW 264.7 Macrophages","volume":"15","author":"Abdallah","year":"2025","journal-title":"Sci. Rep."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"P43","DOI":"10.1186\/ar3644","article-title":"STAT3 Is Critical to Promote Inflammatory Cytokines and RANKL Expression in Inflammatory Arthritis","volume":"14","author":"Miyamoto","year":"2012","journal-title":"Arthritis Res. Ther."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"37S","DOI":"10.1016\/S0002-9343(99)00115-1","article-title":"Role and Regulation of Cyclooxygenase-2 during Inflammation","volume":"106","author":"Simon","year":"1999","journal-title":"Am. J. Med."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1128\/MMBR.00031-10","article-title":"Activation and Function of the MAPKs and Their Substrates, the MAPK-Activated Protein Kinases","volume":"75","author":"Cargnello","year":"2011","journal-title":"Microbiol. Mol. Biol. Rev."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1007\/s00590-025-04261-0","article-title":"Research Progress and Prospect of MAPK Signaling Pathway in Knee Osteoarthritis","volume":"35","author":"Fan","year":"2025","journal-title":"Eur. J. Orthop. Surg. Traumatol."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Ivanova, L., and Karelson, M. (2022). The Impact of Software Used and the Type of Target Protein on Molecular Docking Accuracy. Molecules, 27.","DOI":"10.3390\/molecules27249041"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Chavda, V.P., Feehan, J., and Apostolopoulos, V. (2024). Inflammation: The Cause of All Diseases. Cells, 13.","DOI":"10.3390\/cells13221906"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1038\/s44385-025-00010-4","article-title":"Inflammation: A Matter of Immune Cell Life and Death","volume":"2","author":"Bender","year":"2025","journal-title":"npj Biomed. Innov."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"e2317232120","DOI":"10.1073\/pnas.2317232120","article-title":"Three Common Assumptions about Inflammation, Aging, and Health That Are Probably Wrong","volume":"120","author":"McDade","year":"2023","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"278","DOI":"10.1016\/j.rehab.2010.03.001","article-title":"Non-Steroidal Anti-Inflammatory Drugs for Athletes: An Update","volume":"53","author":"Ziltener","year":"2010","journal-title":"Ann. Phys. Rehabil. Med."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"821","DOI":"10.18433\/J3VW2F","article-title":"Adverse Effects of Nonsteroidal Antiinflammatory Drugs: An Update of Gastrointestinal, Cardiovascular and Renal Complications","volume":"16","author":"Harirforoosh","year":"2014","journal-title":"J. Pharm. Pharm. Sci."},{"key":"ref_35","first-page":"e37080","article-title":"Effects of Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) and Gastroprotective NSAIDs on the Gastrointestinal Tract: A Narrative Review","volume":"15","author":"Sohail","year":"2023","journal-title":"Cureus"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1711","DOI":"10.1056\/NEJMra050541","article-title":"Antiinflammatory Action of Glucocorticoids\u2014New Mechanisms for Old Drugs","volume":"353","author":"Rhen","year":"2005","journal-title":"N. Engl. J. Med."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"2216","DOI":"10.1016\/j.clinthera.2017.09.011","article-title":"Long-Term Systemic Corticosteroid Exposure: A Systematic Literature Review","volume":"39","author":"Rice","year":"2017","journal-title":"Clin. Ther."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"184","DOI":"10.3390\/ddc3010011","article-title":"Plant-Derived Natural Products: A Source for Drug Discovery and Development","volume":"3","author":"Chaachouay","year":"2024","journal-title":"Drugs Drug Candidates"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1186\/s13020-025-01115-z","article-title":"Curcuma longa (Turmeric): From Traditional Applications to Modern Plant Medicine Research Hotspots","volume":"20","author":"Tian","year":"2025","journal-title":"Chin. Med."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"5276130","DOI":"10.1155\/2016\/5276130","article-title":"Role of Antioxidants and Natural Products in Inflammation","volume":"2016","author":"Arulselvan","year":"2016","journal-title":"Oxidative Med. Cell. Longev."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Rodr\u00edguez-Yoldi, M.J. (2021). Anti-Inflammatory and Antioxidant Properties of Plant Extracts. Antioxidants, 10.","DOI":"10.3390\/antiox10060921"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"5445291","DOI":"10.1155\/2022\/5445291","article-title":"Flavonoids a Bioactive Compound from Medicinal Plants and Its Therapeutic Applications","volume":"2022","author":"Roy","year":"2022","journal-title":"BioMed Res. Int."},{"key":"ref_43","first-page":"e020622205552","article-title":"Chemical Composition, Antioxidant, Antimicrobial, and Immunomodulatory Activity of Mandragora Autumnalis Grown in Jordan","volume":"13","author":"Mahmod","year":"2023","journal-title":"Nat. Prod. J."},{"key":"ref_44","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_45","doi-asserted-by":"crossref","first-page":"1143","DOI":"10.1007\/s10753-017-0558-9","article-title":"Chrysin Attenuates IL-1\u03b2-Induced Expression of Inflammatory Mediators by Suppressing NF-\u03baB in Human Osteoarthritis Chondrocytes","volume":"40","author":"Zheng","year":"2017","journal-title":"Inflammation"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"702","DOI":"10.1038\/cmi.2015.107","article-title":"Preventive Effect of Chrysin on Experimental Autoimmune Uveitis Triggered by Injection of Human IRBP Peptide 1\u201320 in Mice","volume":"14","author":"Meng","year":"2017","journal-title":"Cell. Mol. Immunol."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Faheem, M.A., Akhtar, T., Naseem, N., Aftab, U., Zafar, M.S., Hussain, S., Shahzad, M., and Gobe, G.C. (2023). Chrysin Is Immunomodulatory and Anti-Inflammatory against Complete Freund\u2019s Adjuvant-Induced Arthritis in a Pre-Clinical Rodent Model. Pharmaceutics, 15.","DOI":"10.3390\/pharmaceutics15041225"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"5377","DOI":"10.1021\/acsomega.2c06451","article-title":"Attenuation of Lipopolysaccharide-Induced Inflammatory Responses through Inhibition of the NF-\u03baB Pathway and the Increased NRF2 Level by a Flavonol-Enriched n-Butanol Fraction from Uvaria alba","volume":"8","author":"Notarte","year":"2023","journal-title":"ACS Omega"},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Cheng, P., Wang, T., Li, W., Muhammad, I., Wang, H., Sun, X., Yang, Y., Li, J., Xiao, T., and Zhang, X. (2017). Baicalin Alleviates Lipopolysaccharide-Induced Liver Inflammation in Chicken by Suppressing TLR4-Mediated NF-\u03baB Pathway. Front. Pharmacol., 8.","DOI":"10.3389\/fphar.2017.00547"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"2345","DOI":"10.1248\/bpb.30.2345","article-title":"Inhibition of LPS-Induced iNOS, COX-2 and Cytokines Expression by Poncirin through the NF-.KAPPA.B Inactivation in RAW 264.7 Macrophage Cells","volume":"30","author":"Kim","year":"2007","journal-title":"Biol. Pharm. Bull."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1186\/s43141-023-00462-4","article-title":"Repressing Effect of Transformed Ginsenoside Rg3-Mix against LPS-Induced Inflammation in RAW264.7 Macrophage Cells","volume":"21","author":"Marium","year":"2023","journal-title":"J. Genet. Eng. Biotechnol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1126","DOI":"10.1089\/ars.2012.5149","article-title":"Reactive Oxygen Species in Inflammation and Tissue Injury","volume":"20","author":"Mittal","year":"2014","journal-title":"Antioxid. Redox Signal."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1038\/s41420-024-02278-8","article-title":"Free Radicals and Their Impact on Health and Antioxidant Defenses: A Review","volume":"11","author":"Chandimali","year":"2025","journal-title":"Cell Death Discov."},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Ristic-Medic, D., Kovacic, M., Takic, M., Arsic, A., Petrovic, S., Paunovic, M., Jovicic, M., and Vucic, V. (2020). Calorie-Restricted Mediterranean and Low-Fat Diets Affect Fatty Acid Status in Individuals with Nonalcoholic Fatty Liver Disease. Nutrients, 13.","DOI":"10.3390\/nu13010015"},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Mart\u00ednez-Garc\u00eda, M., and Hern\u00e1ndez-Lemus, E. (2025). Pro-Inflammatory and Anti-Inflammatory Interleukins in Periodontitis: Molecular Roles, Immune Crosstalk, and Therapeutic Perspectives. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms262010094"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1038\/s41392-024-01757-9","article-title":"NF-\u03baB in Biology and Targeted Therapy: New Insights and Translational Implications","volume":"9","author":"Guo","year":"2024","journal-title":"Sig. Transduct. Target. Ther."},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Christian, F., Smith, E., and Carmody, R. (2016). The Regulation of NF-\u03baB Subunits by Phosphorylation. Cells, 5.","DOI":"10.3390\/cells5010012"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1038\/s41392-020-00312-6","article-title":"Targeting NF-\u03baB Pathway for the Therapy of Diseases: Mechanism and Clinical Study","volume":"5","author":"Yu","year":"2020","journal-title":"Sig. Transduct. Target. Ther."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1038\/s41392-023-01452-1","article-title":"Macrophages in Immunoregulation and Therapeutics","volume":"8","author":"Chen","year":"2023","journal-title":"Sig. Transduct. Target. Ther."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"679","DOI":"10.1038\/nri3495","article-title":"Mitogen-Activated Protein Kinases in Innate Immunity","volume":"13","author":"Arthur","year":"2013","journal-title":"Nat. Rev. Immunol."},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Santana-G\u00e1lvez, J., Cisneros-Zevallos, L., and Jacobo-Vel\u00e1zquez, D. (2017). Chlorogenic Acid: Recent Advances on Its Dual Role as a Food Additive and a Nutraceutical against Metabolic Syndrome. Molecules, 22.","DOI":"10.3390\/molecules22030358"},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Zalewska, K., Kulawik, M., Gierszewska, J., Gramala, Z., Kalus, O., Karpi\u0144ski, M., Ma\u0107kowiak, J., Staniewski, A., Szyma\u0144ska, Z., and Zalewska, B. (2025). Chlorogenic Acid\u2019s Role in Metabolic Health: Mechanisms and Therapeutic Potential. Nutrients, 17.","DOI":"10.3390\/nu17203303"},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Kopustinskiene, D.M., Jakstas, V., Savickas, A., and Bernatoniene, J. (2020). Flavonoids as Anticancer Agents. Nutrients, 12.","DOI":"10.3390\/nu12020457"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"19","DOI":"10.3831\/KPI.2015.18.002","article-title":"Quercetin Down-Regulates IL-6\/STAT-3 Signals to Induce Mitochondrial-Mediated Apoptosis in a Nonsmall-Cell Lung-Cancer Cell Line, A549","volume":"18","author":"Mukherjee","year":"2015","journal-title":"J. Pharmacopunct."},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Sun, W., and Shahrajabian, M.H. (2023). Therapeutic Potential of Phenolic Compounds in Medicinal Plants\u2014Natural Health Products for Human Health. Molecules, 28.","DOI":"10.3390\/molecules28041845"},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Coniglio, S., Shumskaya, M., and Vassiliou, E. (2023). Unsaturated Fatty Acids and Their Immunomodulatory Properties. Biology, 12.","DOI":"10.3390\/biology12020279"},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Hornung, F., Rogal, J., Loskill, P., L\u00f6ffler, B., and Deinhardt-Emmer, S. (2021). The Inflammatory Profile of Obesity and the Role on Pulmonary Bacterial and Viral Infections. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22073456"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1186\/s43556-025-00338-8","article-title":"ROS Homeostasis in Cell Fate, Pathophysiology, and Therapeutic Interventions","volume":"6","author":"Chen","year":"2025","journal-title":"Mol. Biomed."},{"key":"ref_69","doi-asserted-by":"crossref","unstructured":"Kim, M.E., and Lee, J.S. (2025). Advances in the Regulation of Inflammatory Mediators in Nitric Oxide Synthase: Implications for Disease Modulation and Therapeutic Approaches. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms26031204"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"43140","DOI":"10.1038\/s41598-025-27374-2","article-title":"Improving Quercetin Solubility via Structural Modification Enhances Dual-Target Coronavirus Entry: An Integrated in-Vitro and in-Silico Study","volume":"15","author":"Torabfam","year":"2025","journal-title":"Sci. Rep."},{"key":"ref_71","first-page":"1997","article-title":"ERK\/MAPK Signalling Pathway and Tumorigenesis","volume":"19","author":"Guo","year":"2020","journal-title":"Exp. Ther. Med."},{"key":"ref_72","doi-asserted-by":"crossref","unstructured":"Siti, H.N., Jalil, J., Asmadi, A.Y., and Kamisah, Y. (2021). Rutin Modulates MAPK Pathway Differently from Quercetin in Angiotensin II-Induced H9c2 Cardiomyocyte Hypertrophy. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22105063"},{"key":"ref_73","doi-asserted-by":"crossref","unstructured":"Millan-Casarrubias, E.J., Garc\u00eda-Tejeda, Y.V., Gonz\u00e1lez-De La Rosa, C.H., Ruiz-Maz\u00f3n, L., Hern\u00e1ndez-Rodr\u00edguez, Y.M., and Cigarroa-Mayorga, O.E. (2025). Molecular Docking and Pharmacological in Silico Evaluation of Camptothecin and Related Ligands as Promising HER2-Targeted Therapies for Breast Cancer. Curr. Issues Mol. Biol., 47.","DOI":"10.3390\/cimb47030193"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"13384","DOI":"10.3390\/molecules200713384","article-title":"Molecular Docking and Structure-Based Drug Design Strategies","volume":"20","author":"Ferreira","year":"2015","journal-title":"Molecules"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"e714","DOI":"10.1002\/mco2.714","article-title":"The Interaction of Innate Immune and Adaptive Immune System","volume":"5","author":"Wang","year":"2024","journal-title":"MedComm"},{"key":"ref_76","first-page":"6","article-title":"Sinapis Arvensis-Wild Mustard as an AntiSection Inflammatory Agent: An In-Vitro Study","volume":"16","author":"Ashwini","year":"2022","journal-title":"J. Clin. Diagn. Res."},{"key":"ref_77","doi-asserted-by":"crossref","unstructured":"Moualek, I., Bendif, H., Dekir, A., Benarab, K., Belounis, Y., Elfalleh, W., Houali, K., and Peron, G. (2025). Investigation of In Vitro and In Silico Anti-Inflammatory Potential of Carthamus caeruleus L. Root Juice. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms26135965"},{"key":"ref_78","doi-asserted-by":"crossref","unstructured":"Bamdad, F., Shin, S.H., Suh, J.-W., Nimalaratne, C., and Sunwoo, H. (2017). Anti-Inflammatory and Antioxidant Properties of Casein Hydrolysate Produced Using High Hydrostatic Pressure Combined with Proteolytic Enzymes. Molecules, 22.","DOI":"10.3390\/molecules22040609"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"71","DOI":"10.22159\/ijpps.2019v11i2.30387","article-title":"In Vitro Anti-Inflammatory Activity of Syringic Acid","volume":"11","author":"Chanda","year":"2018","journal-title":"Int. J. Pharm. Pharm. Sci."},{"key":"ref_80","first-page":"395","article-title":"Inhibition of Albumin Denaturation and Anti-Inflammatory Activity of Acetamido [(Phenyl-4\u2032-Yl)-Oxymethyl)]2-(p-Substituted Phenylamino)-1,2,4-Triazoles and -1,3,4-Thiadiazoles","volume":"31","author":"Nargund","year":"1993","journal-title":"Indian. J. Exp. Biol."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"e22972","DOI":"10.1016\/j.heliyon.2023.e22972","article-title":"Unveiling the Therapeutic Potential: Evaluation of Anti-Inflammatory and Antineoplastic Activity of Magnolia Champaca Linn\u2019s Stem Bark Isolate through Molecular Docking Insights","volume":"10","author":"Hasan","year":"2024","journal-title":"Heliyon"},{"key":"ref_82","first-page":"1279359","article-title":"Protective Effect of Bergapten against Human Erythrocyte Hemolysis and Protein Denaturation In Vitro","volume":"2021","author":"Aidoo","year":"2021","journal-title":"Int. J. Inflamm."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1016\/j.jep.2016.04.057","article-title":"Anti-Inflammatory and Anti-Oxidant Effect of Calea urticifolia lyophilized aqueous Extract on Lipopolysaccharide-Stimulated RAW 264.7 Macrophages","volume":"188","author":"Berhow","year":"2016","journal-title":"J. Ethnopharmacol."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1186\/1477-3155-10-19","article-title":"Antibacterial Activities of Gold and Silver Nanoparticles against Escherichia coli and Bacillus Calmette-Gu\u00e9rin","volume":"10","author":"Zhou","year":"2012","journal-title":"J. Nanobiotechnol."}],"container-title":["Pharmaceuticals"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1424-8247\/19\/3\/483\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,16]],"date-time":"2026-03-16T11:24:41Z","timestamp":1773660281000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1424-8247\/19\/3\/483"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,15]]},"references-count":84,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2026,3]]}},"alternative-id":["ph19030483"],"URL":"https:\/\/doi.org\/10.3390\/ph19030483","relation":{},"ISSN":["1424-8247"],"issn-type":[{"value":"1424-8247","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,15]]}}}