{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T12:03:50Z","timestamp":1793275430608,"version":"4.5.0"},"reference-count":45,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2026,1,20]],"date-time":"2026-01-20T00:00:00Z","timestamp":1768867200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Foods"],"abstract":"<jats:p>Numerous research works have tried to evaluate the correlation between inflammation and the onset of prostate cancer. Given the in vitro antioxidant power and the anti-proliferative effects on human prostate cancer cells shown by a Juglans regia L. fresh fruit extract, the aim of this work was the evaluation of its potential in the acute and chronic inflammatory states in vivo, revealing a strong anti-inflammatory activity. In the zymosan-induced edema formation assay, a light and non-significant edema reduction was shown. On the contrary, in the zymosan-induced thermal hyperalgesia assay, the reversion of hyperalgesia after the extract administration was determined. Moreover, in the formalin test, the extract caused a significant decrease in the licking time caused by the aldehyde, especially in the late phase. In silico, quercetin showed the best fit into the enzymatic pocket of AChE (docking score: \u221211.306 Kcal\/mol). Neochlorogenic acid and ellagic acid gave the best docking scores on BChE (\u221210.292 Kcal\/mol and \u221210.054 Kcal\/mol, respectively). Abscisic acid showed a high binding affinity for the glucocorticoid receptor. Finally, quercetin and abscisic acid were quantified to complete the data by HPLC-DAD, giving 0.246 \u00b1 0.003 mg\/g of dried extract and 0.036 \u00b1 0.004 mg\/g of dried extract, respectively.<\/jats:p>","DOI":"10.3390\/foods15020368","type":"journal-article","created":{"date-parts":[[2026,1,20]],"date-time":"2026-01-20T14:57:58Z","timestamp":1768921078000},"page":"368","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Investigating the Anti-Inflammatory Activity of Juglans regia Fresh Fruit Extract"],"prefix":"10.3390","volume":"15","author":[{"given":"Lorenza","family":"Marinaccio","sequence":"first","affiliation":[{"name":"Department of Innovative Technologies in Medicine and Dentistry, University \u201cG. d\u2019Annunzio\u201d of Chieti-Pescara, Via dei Vestini 31, 66100 Chieti, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eleonora","family":"Procino","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, University \u201cG. d\u2019Annunzio\u201d of Chieti-Pescara, Via dei Vestini 31, 66100 Chieti, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giulia","family":"Gentile","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, University \u201cG. d\u2019Annunzio\u201d of Chieti-Pescara, Via dei Vestini 31, 66100 Chieti, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5926-6194","authenticated-orcid":false,"given":"Stefano","family":"Pieretti","sequence":"additional","affiliation":[{"name":"National Centre for Drug Research and Evaluation, Istituto Superiore di Sanit\u00e0, 00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2987-5738","authenticated-orcid":false,"given":"Angelo","family":"Cichelli","sequence":"additional","affiliation":[{"name":"Department of Innovative Technologies in Medicine and Dentistry, University \u201cG. d\u2019Annunzio\u201d of Chieti-Pescara, Via dei Vestini 31, 66100 Chieti, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7242-4860","authenticated-orcid":false,"given":"Adriano","family":"Mollica","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, University \u201cG. d\u2019Annunzio\u201d of Chieti-Pescara, Via dei Vestini 31, 66100 Chieti, Italy"},{"name":"SCM Nutraceutici Universitari srl, Strada degli Oliveti 73, 66100 Chieti, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7525-2913","authenticated-orcid":false,"given":"Azzurra","family":"Stefanucci","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, University \u201cG. d\u2019Annunzio\u201d of Chieti-Pescara, Via dei Vestini 31, 66100 Chieti, Italy"},{"name":"SCM Nutraceutici Universitari srl, Strada degli Oliveti 73, 66100 Chieti, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,20]]},"reference":[{"key":"ref_1","first-page":"683","article-title":"Budding and Grafting of the Walnut (Juglans regia L.) and Their Effectiveness in Bulgaria (Review)","volume":"13","author":"Gandev","year":"2007","journal-title":"Bulgar. J. Agri. Sci."},{"key":"ref_2","first-page":"5796","article-title":"Utility and Importance of Walnut, Juglans regia Linn: A Review","volume":"5","author":"Taha","year":"2011","journal-title":"Afr. J. Microbiol. Res."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1959","DOI":"10.1002\/jsfa.4059","article-title":"Walnut (Juglans regia L.): Genetic Resources, Chemistry, by-Products","volume":"90","author":"Labuckas","year":"2010","journal-title":"J. Sci. Food Agric."},{"key":"ref_4","first-page":"390","article-title":"Juglans regia: A Review of Its Traditional Uses Phytochemistry and Pharmacology","volume":"7","author":"Jaiswal","year":"2017","journal-title":"Indo Am. J. Pharm. Res."},{"key":"ref_5","first-page":"27","article-title":"Antinociceptive, Anti-Inflammatory and Acute Toxicity Effects of Juglans regia L. Leaves in Mice","volume":"13","author":"Hosseinzadeh","year":"2011","journal-title":"Iran. Red. Crescent Med. J."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1695701","DOI":"10.1155\/2022\/1695701","article-title":"Preclinical Rodent Models of Arthritis and Acute Inflammation Indicate Immunomodulatory and Anti-Inflammatory Properties of Juglans regia Extracts","volume":"2022","author":"Mobashar","year":"2022","journal-title":"Evid.-Based Complement. Altern. Med."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Fize\u0219an, I., Rusu, M.E., Georgiu, C., Pop, A., \u0218tefan, M.-G., Muntean, D.-M., Mirel, S., Vostinaru, O., Kiss, B., and Popa, D.-S. (2021). Antitussive, Antioxidant, and Anti-Inflammatory Effects of a Walnut (Juglans regia L.) Septum Extract Rich in Bioactive Compounds. Antioxidants, 10.","DOI":"10.3390\/antiox10010119"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"103539","DOI":"10.1016\/j.fbio.2023.103539","article-title":"Assessment of the In-Vitro Toxicity and In-Vivo Therapeutic Capabilities of Juglans regia on Human Prostate Cancer and Prostatic Hyperplasia in Rats","volume":"57","author":"Stefanucci","year":"2024","journal-title":"Food Biosci."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1016\/j.eururo.2006.06.008","article-title":"Detection of Escherichia coli 16S RNA and Cytotoxic Necrotizing Factor 1 Gene in Benign Prostate Hyperplasia","volume":"51","author":"Bergh","year":"2007","journal-title":"Eur. Urol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1111\/j.1365-2559.2011.04033.x","article-title":"Prostate Cancer and Inflammation: The Evidence","volume":"60","author":"Sfanos","year":"2012","journal-title":"Histopathology"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"256","DOI":"10.1038\/nrc2090","article-title":"Inflammation in Prostate Carcinogenesis","volume":"7","author":"Platz","year":"2007","journal-title":"Nat. Rev. Cancer"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1016\/S0090-4295(02)01637-0","article-title":"Epidemiologic Association between Prostatitis and Prostate Cancer","volume":"60","author":"Dennis","year":"2002","journal-title":"Urology"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1170","DOI":"10.1093\/carcin\/bgh317","article-title":"Prostate Carcinogenesis and Inflammation: Emerging Insights","volume":"26","author":"Palapattu","year":"2005","journal-title":"Carcinogenesis"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Pieretti, S., Saviano, A., Mollica, A., Stefanucci, A., Aloisi, A.M., and Nicoletti, M. (2022). Calceolarioside A, a Phenylpropanoid Glycoside from Calceolaria Spp., Displays Antinociceptive and Anti-Inflammatory Properties. Molecules, 27.","DOI":"10.3390\/molecules27072183"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"108698","DOI":"10.1016\/j.cbi.2019.06.011","article-title":"A New Crystal Form of Human Acetylcholinesterase for Exploratory Room-Temperature Crystallography Studies","volume":"309","author":"Gerlits","year":"2019","journal-title":"Chem.-Biol. Interact."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Rosenberry, T.L., Brazzolotto, X., Macdonald, I.R., Wandhammer, M., Trovaslet-Leroy, M., Darvesh, S., and Nachon, F. (2017). Comparison of the Binding of Reversible Inhibitors to Human Butyrylcholinesterase and Acetylcholinesterase: A Crystallographic, Kinetic and Calorimetric Study. Molecules, 22.","DOI":"10.3390\/molecules22122098"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2280","DOI":"10.1016\/j.str.2015.09.012","article-title":"Ligand Binding Mechanism in Steroid Receptors: From Conserved Plasticity to Differential Evolutionary Constraints","volume":"23","author":"Edman","year":"2015","journal-title":"Structure"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Sinan, K.I., Yagi, S., Llorent-Mart\u00ednez, E.J., Ruiz-Medina, A., Gordo-Moreno, A.I., Stefanucci, A., Mollica, A., Bene, K., and Zengin, G. (2023). Understanding the Chemical Composition and Biological Activities of Different Extracts of Secamone Afzelii Leaves: A Potential Source of Bioactive Compounds for the Food Industry. Molecules, 28.","DOI":"10.3390\/molecules28093678"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Stefanucci, A., Iobbi, V., Della Valle, A., Scioli, G., Pieretti, S., Minosi, P., Mirzaie, S., Novellino, E., and Mollica, A. (2021). In Silico Identification of Tripeptides as Lead Compounds for the Design of KOR Ligands. Molecules, 26.","DOI":"10.3390\/molecules26164767"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"108157","DOI":"10.1016\/j.compbiolchem.2024.108157","article-title":"Discovering Novel Targets of Abscisic Acid Using Computational Approaches","volume":"112","author":"Iranmanesh","year":"2024","journal-title":"Comput. Biol. Chem."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"e70053","DOI":"10.1002\/fsn3.70053","article-title":"Hypericum empetrifolium and H. lydium as Health Promoting Nutraceuticals: Assessing Their Role Combining in Vitro in Silico and Chemical Approaches","volume":"13","author":"Sut","year":"2025","journal-title":"Food Sci. Nutr."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Mamadalieva, N.Z., Youssef, F.S., Hussain, H., Zengin, G., Mollica, A., Al Musayeib, N.M., Ashour, M.L., Westermann, B., and Wessjohann, L.A. (2021). Validation of the Antioxidant and Enzyme Inhibitory Potential of Selected Triterpenes Using in Vitro and in Silico Studies, and the Evaluation of Their ADMET Properties. Molecules, 26.","DOI":"10.3390\/molecules26216331"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1007\/s00289-022-04091-8","article-title":"An Insight into Anticancer, Antioxidant, Antimicrobial, Antidiabetic and Anti-Inflammatory Effects of Quercetin: A Review","volume":"80","author":"Azeem","year":"2023","journal-title":"Polym. Bull."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1146\/annurev.arplant.49.1.199","article-title":"Abscisic Acid Signal Transduction","volume":"49","author":"Leung","year":"1998","journal-title":"Annu. Rev. Plant. Physiol. Plant. Mol. Biol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1146\/annurev.arplant.56.032604.144046","article-title":"Abscisic Acid Biosynthesis and Catabolism","volume":"56","author":"Nambara","year":"2005","journal-title":"Annu. Rev. Plant Biol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1007\/s11738-024-03730-z","article-title":"Hormonal, Biochemical, and Genetic Regulations of Walnut Fruit Development and Ripening: An Integrated Perspective","volume":"46","author":"Kumar","year":"2024","journal-title":"Acta Physiol. Plant."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"581","DOI":"10.1007\/s00709-015-0836-z","article-title":"Fruit Ripening Mutants Reveal Cell Metabolism and Redox State during Ripening","volume":"253","author":"Kumar","year":"2016","journal-title":"Protoplasma"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"4577","DOI":"10.1093\/jxb\/eru204","article-title":"The Role of Abscisic Acid in Fruit Ripening and Responses to Abiotic Stress","volume":"65","author":"Leng","year":"2013","journal-title":"J. Exp. Bot."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"824","DOI":"10.1016\/j.clnu.2010.02.009","article-title":"Abscisic Acid Ameliorates Experimental IBD by Downregulating Cellular Adhesion Molecule Expression and Suppressing Immune Cell Infiltration","volume":"29","author":"Guri","year":"2010","journal-title":"Clin. Nutr."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"730","DOI":"10.1016\/S0014-827X(00)00094-X","article-title":"Structure\u2013Activity Relationships for the Analgesic Activity of Gallic Acid Derivatives","volume":"55","author":"Krogh","year":"2000","journal-title":"Il Farm."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Yang, R., Li, Z., Zou, Y., Yang, J., Li, L., Xu, X., Schmalzing, G., Nie, H., Li, G., and Liu, S. (2021). Gallic Acid Alleviates Neuropathic Pain Behaviors in Rats by Inhibiting P2X7 Receptor-Mediated NF-\u03baB\/STAT3 Signaling Pathway. Front. Pharmacol., 12.","DOI":"10.3389\/fphar.2021.680139"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"380","DOI":"10.1016\/j.arcmed.2020.12.005","article-title":"Gallic Acid Exerts Nephroprotective, Anti-Oxidative Stress, and Anti-Inflammatory Effects Against Diclofenac-Induced Renal Injury in Malerats","volume":"52","author":"Moradi","year":"2021","journal-title":"Arch. Med. Res."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1007\/s00011-013-0602-7","article-title":"Dietary Component P-Coumaric Acid Suppresses Monosodium Urate Crystal-Induced Inflammation in Rats","volume":"62","author":"Pragasam","year":"2013","journal-title":"Inflamm. Res."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Guilherme, V.A., Cunha, V.R.R., De Paula, E., De Araujo, D.R., and Constantino, V.R.L. (2022). Anti-Inflammatory and Analgesic Evaluation of a Phytochemical Intercalated into Layered Double Hydroxide. Pharmaceutics, 14.","DOI":"10.3390\/pharmaceutics14050934"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"54","DOI":"10.22159\/ijap.2019v11i5.33191","article-title":"Formulation and Evaluation of Quercetin Nanoparticle Gel for Osteoarthritis","volume":"11","author":"Karliana","year":"2019","journal-title":"Int. J. Appl. Pharm."},{"key":"ref_36","first-page":"888","article-title":"Anti-inflammatory Effect of Quercetin and Galangin in LPS-stimulated RAW264.7 Macrophages and DNCB-induced Atopic Dermatitis Animal Models","volume":"41","author":"Lee","year":"2018","journal-title":"Int. J. Mol. Med."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Huang, J., Xie, M., He, L., Song, X., and Cao, T. (2023). Chlorogenic Acid: A Review on Its Mechanisms of Anti-Inflammation, Disease Treatment, and Related Delivery Systems. Front. Pharmacol., 14.","DOI":"10.3389\/fphar.2023.1218015"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"2236","DOI":"10.1248\/bpb.29.2236","article-title":"Evaluation of the Anti-Inflammatory, Analgesic and Antipyretic Activities of the Natural Polyphenol Chlorogenic Acid","volume":"29","author":"Almeida","year":"2006","journal-title":"Biol. Pharm. Bull."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1792","DOI":"10.1007\/s11064-015-1659-1","article-title":"Neochlorogenic Acid Inhibits Lipopolysaccharide-Induced Activation and Pro-Inflammatory Responses in BV2 Microglial Cells","volume":"40","author":"Kim","year":"2015","journal-title":"Neurochem. Res."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"108020","DOI":"10.1016\/j.neuropharm.2020.108020","article-title":"Central and Peripheral Anti-Inflammatory Effects of Acetylcholinesterase Inhibitors","volume":"168","author":"Vaknine","year":"2020","journal-title":"Neuropharmacology"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"458","DOI":"10.1038\/35013070","article-title":"Vagus Nerve Stimulation Attenuates the Systemic Inflammatory Response to Endotoxin","volume":"405","author":"Borovikova","year":"2000","journal-title":"Nature"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"448","DOI":"10.1016\/j.tins.2015.05.007","article-title":"Checks and Balances on Cholinergic Signaling in Brain and Body Function","volume":"38","author":"Soreq","year":"2015","journal-title":"Trends Neurosci."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"812","DOI":"10.1016\/j.jnutbio.2010.06.011","article-title":"T Cell PPAR\u03b3 Is Required for the Anti-Inflammatory Efficacy of Abscisic Acid against Experimental IBD","volume":"22","author":"Guri","year":"2011","journal-title":"J. Nutr. Biochem."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Nazir, N., Zahoor, M., Nisar, M., Karim, N., Latif, A., Ahmad, S., and Uddin, Z. (2020). Evaluation of neuroprotective and anti-amnesic effects of Elaeagnus umbellata Thunb. On scopolamine-induced memory impairment in mice. BMC Complement. Med. Ther., 20.","DOI":"10.1186\/s12906-020-02942-3"},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Liao, Y., Mai, X., Wu, X., Hu, X., Luo, X., and Zhang, G. (2022). Exploring the Inhibition of Quercetin on Acetylcholinesterase by Multispectroscopic and in Silico Approaches and Evaluation of Its Neuroprotective Effects on PC12 Cells. Molecules, 27.","DOI":"10.3390\/molecules27227971"}],"container-title":["Foods"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2304-8158\/15\/2\/368\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,22]],"date-time":"2026-01-22T05:18:18Z","timestamp":1769059098000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2304-8158\/15\/2\/368"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,20]]},"references-count":45,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2026,1]]}},"alternative-id":["foods15020368"],"URL":"https:\/\/doi.org\/10.3390\/foods15020368","relation":{},"ISSN":["2304-8158"],"issn-type":[{"value":"2304-8158","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,20]]}}}