{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T18:46:37Z","timestamp":1790016397820,"version":"4.0.1"},"reference-count":30,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T00:00:00Z","timestamp":1773014400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Male accessory gland inflammation (MAGI) can impair male fertility through inflammation-driven oxidative stress and direct sperm damage; nutraceutical approaches may be useful when antibiotics are not indicated. Here, we evaluated a 3-month treatment with a Graminex\u2122-based dietary supplement (Deprox-HP) in twenty MAGI patients integrating conventional semen analysis and oxidative stress assessment with sperm proteomics before and after therapy. After treatment, total and progressive sperm motility increased significantly, whereas sperm concentration and sperm morphology showed a non-significant upward trend. Sperm lipid peroxidation decreased markedly, while the antioxidant capacity showed a non-significant increase. Analysis of the sperm proteome demonstrated a clear PRE\u2013POST clustering, consistent with treatment-associated remodeling. POST samples showed upregulation of proteins linked to sperm motility, redox homeostasis, mitochondrial metabolism and membrane remodeling. Two pregnancies occurred during the treatment period; in both cases, lipid peroxidation decreased along with an increase of morphologically typical spermatozoa, and sperm proteomics showed a concordant post-treatment shift enriched in flagellar and mitochondrial respiratory\/redox compartments. Moreover, we found a selective enrichment POST treatment in these two patients of TEX50, a crucial protein involved in acrosome\/head-stability during epididymal transit. Overall, Deprox-HP was associated with reduced oxidative membrane damage and a coordinated sperm proteomic shift consistent with improved motility.<\/jats:p>","DOI":"10.3390\/ijms27052498","type":"journal-article","created":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T10:16:12Z","timestamp":1773051372000},"page":"2498","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Seminal Redox Improvement and Sperm Proteome Remodeling After Deprox-HP Nutraceutical Supplementation in Male Accessory Gland Inflammation: A Pilot Study"],"prefix":"10.3390","volume":"27","author":[{"given":"Fiorella","family":"Di Nicuolo","sequence":"first","affiliation":[{"name":"Unit of Chemistry, Biochemistry and Molecular Biology, \u201cA. Gemelli\u201d Hospital Foundation IRCCS, Largo A. Gemelli, 8, 00168 Rome, Italy"},{"name":"International Scientific Institute Paul VI, Universit\u00e0 Cattolica del Sacro Cuore, Fondazione Policlinico Universitario \u201cA. Gemelli\u201d IRCCS, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandro","family":"Oliva","sequence":"additional","affiliation":[{"name":"Complex Operative Unit of Internal Medicine, Endocrinology and Diabetology, Department of Translational Medicine and Surgery, Fondazione Policlinico Universitario \u201cA. Gemelli\u201d IRCCS, 00168 Rome, Italy"},{"name":"Department of Medicine and Translational Surgery, General Pathology Section, Universit\u00e0 Cattolica del Sacro Cuore, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emanuele Pierpaolo","family":"Vodola","sequence":"additional","affiliation":[{"name":"Complex Operative Unit of Internal Medicine, Endocrinology and Diabetology, Department of Translational Medicine and Surgery, Fondazione Policlinico Universitario \u201cA. Gemelli\u201d IRCCS, 00168 Rome, Italy"},{"name":"Department of Medicine and Translational Surgery, General Pathology Section, Universit\u00e0 Cattolica del Sacro Cuore, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-8975-4947","authenticated-orcid":false,"given":"Michela","family":"Cicchinelli","sequence":"additional","affiliation":[{"name":"Unit of Chemistry, Biochemistry and Molecular Biology, \u201cA. Gemelli\u201d Hospital Foundation IRCCS, Largo A. Gemelli, 8, 00168 Rome, Italy"},{"name":"Department of Basic Biotechnological Sciences, Intensive and Perioperative Clinics, Universit\u00e0 Cattolica del Sacro Cuore, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2074-5531","authenticated-orcid":false,"given":"Federica","family":"Iavarone","sequence":"additional","affiliation":[{"name":"Unit of Chemistry, Biochemistry and Molecular Biology, \u201cA. Gemelli\u201d Hospital Foundation IRCCS, Largo A. Gemelli, 8, 00168 Rome, Italy"},{"name":"Department of Basic Biotechnological Sciences, Intensive and Perioperative Clinics, Universit\u00e0 Cattolica del Sacro Cuore, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carla","family":"Di Nardo","sequence":"additional","affiliation":[{"name":"Complex Operative Unit of Internal Medicine, Endocrinology and Diabetology, Department of Translational Medicine and Surgery, Fondazione Policlinico Universitario \u201cA. Gemelli\u201d IRCCS, 00168 Rome, Italy"},{"name":"Department of Medicine and Translational Surgery, General Pathology Section, Universit\u00e0 Cattolica del Sacro Cuore, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8444-0091","authenticated-orcid":false,"given":"Edoardo","family":"Vergani","sequence":"additional","affiliation":[{"name":"Complex Operative Unit of Internal Medicine, Endocrinology and Diabetology, Department of Translational Medicine and Surgery, Fondazione Policlinico Universitario \u201cA. Gemelli\u201d IRCCS, 00168 Rome, Italy"},{"name":"Department of Medicine and Translational Surgery, General Pathology Section, Universit\u00e0 Cattolica del Sacro Cuore, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paola","family":"Girardi","sequence":"additional","affiliation":[{"name":"Complex Operative Unit of Internal Medicine, Endocrinology and Diabetology, Department of Translational Medicine and Surgery, Fondazione Policlinico Universitario \u201cA. Gemelli\u201d IRCCS, 00168 Rome, Italy"},{"name":"Department of Medicine and Translational Surgery, General Pathology Section, Universit\u00e0 Cattolica del Sacro Cuore, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Mancini","sequence":"additional","affiliation":[{"name":"Unit of Chemistry, Biochemistry and Molecular Biology, \u201cA. Gemelli\u201d Hospital Foundation IRCCS, Largo A. Gemelli, 8, 00168 Rome, Italy"},{"name":"International Scientific Institute Paul VI, Universit\u00e0 Cattolica del Sacro Cuore, Fondazione Policlinico Universitario \u201cA. Gemelli\u201d IRCCS, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alfredo","family":"Pontecorvi","sequence":"additional","affiliation":[{"name":"Complex Operative Unit of Internal Medicine, Endocrinology and Diabetology, Department of Translational Medicine and Surgery, Fondazione Policlinico Universitario \u201cA. Gemelli\u201d IRCCS, 00168 Rome, Italy"},{"name":"Department of Medicine and Translational Surgery, General Pathology Section, Universit\u00e0 Cattolica del Sacro Cuore, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Urbani","sequence":"additional","affiliation":[{"name":"Unit of Chemistry, Biochemistry and Molecular Biology, \u201cA. Gemelli\u201d Hospital Foundation IRCCS, Largo A. Gemelli, 8, 00168 Rome, Italy"},{"name":"Department of Basic Biotechnological Sciences, Intensive and Perioperative Clinics, Universit\u00e0 Cattolica del Sacro Cuore, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-8528-7533","authenticated-orcid":false,"given":"Silvia","family":"Baroni","sequence":"additional","affiliation":[{"name":"Unit of Chemistry, Biochemistry and Molecular Biology, \u201cA. Gemelli\u201d Hospital Foundation IRCCS, Largo A. Gemelli, 8, 00168 Rome, Italy"},{"name":"Department of Basic Biotechnological Sciences, Intensive and Perioperative Clinics, Universit\u00e0 Cattolica del Sacro Cuore, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Domenico","family":"Milardi","sequence":"additional","affiliation":[{"name":"Complex Operative Unit of Internal Medicine, Endocrinology and Diabetology, Department of Translational Medicine and Surgery, Fondazione Policlinico Universitario \u201cA. Gemelli\u201d IRCCS, 00168 Rome, Italy"},{"name":"Department of Medicine and Translational Surgery, General Pathology Section, Universit\u00e0 Cattolica del Sacro Cuore, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emanuela","family":"Teveroni","sequence":"additional","affiliation":[{"name":"Unit of Chemistry, Biochemistry and Molecular Biology, \u201cA. Gemelli\u201d Hospital Foundation IRCCS, Largo A. Gemelli, 8, 00168 Rome, Italy"},{"name":"Department of Basic Biotechnological Sciences, Intensive and Perioperative Clinics, Universit\u00e0 Cattolica del Sacro Cuore, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e330","DOI":"10.1111\/j.1365-2605.2011.01200.x","article-title":"Male accessory gland infection and sperm parameters","volume":"34","author":"Vicari","year":"2011","journal-title":"Int. J. Androl."},{"key":"ref_2","first-page":"219","article-title":"Semen alterations and flow-cytometry evaluation in patients with male accessory gland infections","volume":"35","author":"Condorelli","year":"2012","journal-title":"J. Endocrinol. Investig."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1298","DOI":"10.1111\/andr.13011","article-title":"Ultrasound evaluation of patients with male accessory gland inflammation: A pictorial review","volume":"9","author":"Crafa","year":"2021","journal-title":"Andrology"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1064","DOI":"10.1111\/andr.12427","article-title":"Male accessory gland inflammation, infertility, and sexual dysfunctions: A practical approach to diagnosis and therapy","volume":"5","author":"Calogero","year":"2017","journal-title":"Andrology"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Barbagallo, F., and La Vignera, S. (2020). Evaluation of sperm mitochondrial function: Key organelle for sperm motility. J. Clin. Med., 9.","DOI":"10.3390\/jcm9020363"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"464","DOI":"10.1111\/and.12408","article-title":"Seminal parameters of chronic male genital inflammation are associated with disturbed sperm DNA integrity","volume":"47","author":"Haidl","year":"2015","journal-title":"Andrologia"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"325","DOI":"10.2164\/jandrol.106.001149","article-title":"Inflammatory mediators exert toxic effects of oxidative stress on human spermatozoa","volume":"28","author":"Kurpisz","year":"2007","journal-title":"J. Androl."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1016\/S0300-483X(99)00107-9","article-title":"Hydrogen peroxide induces premature acrosome reaction in rat sperm and reduces their penetration of the zona pellucida","volume":"139","author":"Hsu","year":"1999","journal-title":"Toxicology"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"829","DOI":"10.1016\/S0015-0282(02)04948-8","article-title":"Role of reactive oxygen species in the pathophysiology of human reproduction","volume":"79","author":"Agarwal","year":"2003","journal-title":"Fertil. Steril."},{"key":"ref_10","first-page":"60","article-title":"The role of oxidative stress and antioxidants in male fertility","volume":"66","author":"Wolski","year":"2013","journal-title":"Cent. Eur. J. Urol."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Sharifi-Rad, M., and Anil Kumar, N.V. (2020). Lifestyle, Oxidative Stress, and Antioxidants: Back and Forth in the Pathophysiology of Chronic Diseases. Front. Physiol., 11.","DOI":"10.3389\/fphys.2020.00694"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"385","DOI":"10.5713\/ab.22.0325","article-title":"Role of antioxidants in fertility preservation of sperm\u2014A narrative review","volume":"36","author":"Qamar","year":"2023","journal-title":"Anim. Biosci."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Cical\u0103u, G.I.P., and Babes, P.A. (2021). Anti-Inflammatory and Antioxidant Properties of Carvacrol and Magnolol in Periodontal Disease and Diabetes Mellitus. Molecules, 26.","DOI":"10.3390\/molecules26226899"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1007\/BF03349172","article-title":"Sperm parameter abnormalities, low seminal fructose and reactive oxygen species overproduction do not discriminate patients with unilateral or bilateral post-infectious inflammatory prostato-vesiculo-epididymitis","volume":"29","author":"Vicari","year":"2006","journal-title":"J. Endocrinol. Investig."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"e2507930122","DOI":"10.1073\/pnas.2507930122","article-title":"Testis expressed 50 is essential for maintaining sperm acrosome integrity during epididymal transit","volume":"122","author":"Haga","year":"2025","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"e13922","DOI":"10.1111\/and.13743","article-title":"The role of infections and leukocytes in male infertility","volume":"53","author":"Henkel","year":"2021","journal-title":"Andrologia"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1111\/j.1439-0272.1999.tb02837.x","article-title":"Lipid peroxidation in human spermatozoa and maintenance of progressive sperm motility","volume":"31","author":"Engel","year":"1999","journal-title":"Andrologia"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"3257","DOI":"10.1007\/s00345-023-04472-2","article-title":"The role of seminal reactive oxygen species assessment in the setting of infertility and early pregnancy loss","volume":"41","author":"Davies","year":"2023","journal-title":"World J. Urol."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Wang, Y., and Fu, X. (2025). Mechanisms of oxidative stress-induced sperm dysfunction. Front. Endocrinol., 16.","DOI":"10.3389\/fendo.2025.1520835"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1016\/bs.acc.2019.08.004","article-title":"Exosomes of male reproduction","volume":"95","author":"Baskaran","year":"2020","journal-title":"Adv. Clin. Chem."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"R1","DOI":"10.1530\/REP-13-0358","article-title":"Prostasomes: Extracellular vesicles from the prostate","volume":"147","author":"Aalberts","year":"2014","journal-title":"Reproduction"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"106853","DOI":"10.1016\/j.anireprosci.2021.106853","article-title":"Extracellular vesicles in seminal fluid and effects on male reproduction","volume":"246","author":"Roca","year":"2022","journal-title":"Anim. Reprod. Sci."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"101207","DOI":"10.1016\/j.plipres.2022.101207","article-title":"Compartmentalized regulation of lipid signaling in oxidative stress and inflammation: Plasmalogens, oxidized lipids and ferroptosis as new paradigms of bioactive lipid research","volume":"89","author":"Astudillo","year":"2023","journal-title":"Prog. Lipid Res."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"230","DOI":"10.4103\/1008-682X.135123","article-title":"Oxidative phosphorylation versus glycolysis: What fuel do spermatozoa use?","volume":"17","author":"Agarwal","year":"2015","journal-title":"Asian J. Androl."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Xie, Y., and Peng, C. (2025). Seminal plasma extracellular vesicles: Key mediators of male reproduction. Vet. Sci., 12.","DOI":"10.20944\/preprints202504.1653.v1"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1080\/19396368.2020.1867665","article-title":"Extracellular vesicle cargo of the male reproductive tract and the paternal preconception environment","volume":"67","author":"Ayaz","year":"2021","journal-title":"Syst. Biol. Reprod. Med."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Voros, C., and Chatzinikolaou, F. (2025). Sperm-Derived Extracellular Vesicles (Sperm-EVs), Emerging Biomarkers and Functional Modulators in Male Infertility and Assisted Reproduction. Genes, 16.","DOI":"10.3390\/genes16121400"},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Locatelli, M., and Macchione, N. (2018). Graminex Pollen: Phenolic Pattern, Colorimetric Analysis and Protective Effects in Immortalized Prostate Cells (PC3) and Rat Prostate Challenged with LPS. Molecules, 23.","DOI":"10.3390\/molecules23051145"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Muraca, L., and Scuteri, A. (2022). Effectiveness and Safety of a New Nutrient Fixed Combination Containing Pollen Extract Plus Teupolioside, in the Management of LUTS in Patients with Benign Prostatic Hypertrophy: A Pilot Study. Life, 12.","DOI":"10.3390\/life12070965"},{"key":"ref_30","unstructured":"World Health Organization (WHO) (2021). WHO Laboratory Manual for the Examination and Processing of Human Semen, World Health Organization. [6th ed.]."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/5\/2498\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T13:27:41Z","timestamp":1773062861000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/5\/2498"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,9]]},"references-count":30,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2026,3]]}},"alternative-id":["ijms27052498"],"URL":"https:\/\/doi.org\/10.3390\/ijms27052498","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,9]]}}}