{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T00:42:25Z","timestamp":1760143345935,"version":"build-2065373602"},"reference-count":23,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2024,1,25]],"date-time":"2024-01-25T00:00:00Z","timestamp":1706140800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Sanugen srl"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Medicina"],"abstract":"<jats:p>Background and Objectives: Inflammation and oxidative stress have been described to reduce the chance for pregnancy instauration and maintenance. NOFLAMOX, a recently developed herbal preparation with recognized antioxidant and anti-inflammatory properties, can represent an interesting treatment to increase the chance of pregnancy, both physiological or after in vitro fertilization (IVF). The aim of this study was to assess NOFLAMOX\u2019s effect; a population with unexplained infertility was screened for the recently described IMMUNOX panel based on four immunological biomarkers with a prospective study approach. Materials and Methods: Patients with unexplained infertility and positive for at least one of the biomarkers of the IMMUNOX panel were included in this study and treated with NOFLAMOX for three months prior to an IVF cycle. Results: Eighty-six patients (n = 86) were screened with the IMMUNOX panel and the forty-seven (54.5%) found positive were included in this study. In more detail, 11 were positive for TNF\u03b1 (23.4%), 18 (38.3%) for glycodelin (GLY), 29 (61.7%) for Total Oxidative Status (TOS), and 32 (68.1%) for Complement Activity Toxic Factor (CATF). After three months of treatment, a significant reduction in the number of IMMUNOX-positive patients was observable, with 26 patients who turned IMMUNOX-negative displaying a quantitative statistically significant variation of 100% (11\/11), 38.9% (7\/18), 65.5% (18\/29), and 75% (24\/32), for TNF\u03b1, glycodelin, TOS, and CATF, respectively. Followed in the subsequent IVF cycle, this NOFLAMOX-treated population showed a pregnancy rate of 42.3% compared to the 4.7% of the IMMUNOX-positive group of patients. Conclusions: Taken together, the results of this study suggest that NOFLAMOX could represent an interesting option for those patients with unexplained infertility of inflammatory\/oxidative origin. Further studies are needed to confirm these results and explore possible strategies to restore fertility in women with immune-mediated sterility.<\/jats:p>","DOI":"10.3390\/medicina60020204","type":"journal-article","created":{"date-parts":[[2024,1,25]],"date-time":"2024-01-25T03:59:42Z","timestamp":1706155182000},"page":"204","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A Pilot Prospective Study Evaluating the Effect of Curcuma-Based Herbal Food Supplement on the Outcome of In Vitro Fertilization in Patients Testing Positive for Four Immunological Biomarkers"],"prefix":"10.3390","volume":"60","author":[{"given":"Renato","family":"Colognato","sequence":"first","affiliation":[{"name":"Sanugen S.r.l., 21040 Gerenzano, VA, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Incoronata","family":"Laurenza","sequence":"additional","affiliation":[{"name":"Sanugen S.r.l., 21040 Gerenzano, VA, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gabriele","family":"Ersettigh","sequence":"additional","affiliation":[{"name":"Policlinico San Marco, 24046 Zingonia, BG, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giada Antonia","family":"Aiello","sequence":"additional","affiliation":[{"name":"Toma Institute S.r.l., 80139 Naples, NA, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2292-5288","authenticated-orcid":false,"given":"Marta","family":"Carnovali","sequence":"additional","affiliation":[{"name":"IRCCS Ospedale Galeazzi-Sant\u2019Ambrogio, 20157 Milano, MI, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Massimo","family":"Mariotti","sequence":"additional","affiliation":[{"name":"IRCCS Ospedale Galeazzi-Sant\u2019Ambrogio, 20157 Milano, MI, Italy"},{"name":"Department of Biomedical, Surgical and Dental Sciences, University of Milan, 20122 Milano, MI, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicoletta","family":"Maxia","sequence":"additional","affiliation":[{"name":"Policlinico San Marco, 24046 Zingonia, BG, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,1,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.jri.2015.03.003","article-title":"Immunology in reproduction","volume":"108","author":"Markert","year":"2015","journal-title":"J. Reprod. Immunol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1177\/1933719108330087","article-title":"Inflammation in reproductive disorders","volume":"16","author":"Weiss","year":"2009","journal-title":"Reprod. Sci."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1016\/S1382-6689(01)00099-0","article-title":"Antioxidants and reactive oxygen species in human fertility","volume":"10","author":"Taylor","year":"2001","journal-title":"Environ. Toxicol. Pharmacol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"338","DOI":"10.1016\/S1472-6483(10)62151-7","article-title":"Role of free radicals in female reproductive diseases and assisted reproduction","volume":"9","author":"Agarwal","year":"2004","journal-title":"Reprod. Biomed. Online"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"715","DOI":"10.1016\/j.rbmo.2017.08.018","article-title":"Effect of micronutrient supplementation on IVF outcomes: A systematic review of the literature","volume":"35","author":"Arhin","year":"2017","journal-title":"Reprod. Biomed. Online"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Luddi, A., Capaldo, A., Focarelli, R., Gori, M., Morgante, G., Piomboni, P., and De Leo, V. (2016). Antioxidants reduce oxidative stress in follicular fluid of aged women undergoing IVF. Biol. Endocrinol., 14.","DOI":"10.1186\/s12958-016-0184-7"},{"key":"ref_7","first-page":"129","article-title":"Can unexplained infertility be evaluated by a new immunological four biomarkers panel? A pilot study","volume":"70","author":"Maxia","year":"2018","journal-title":"Minerva Ginecol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1208\/s12248-012-9432-8","article-title":"Therapeutic roles of curcumin: Lessons learned from clinical trials","volume":"15","author":"Gupta","year":"2013","journal-title":"AAPS J."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1016\/j.canlet.2009.03.003","article-title":"Bromelain inhibits COX-2 expression by blocking the activation of MAPK regulated NF-kappa B against skin tumor-initiation triggering mitochondrial death pathway","volume":"282","author":"Bhui","year":"2009","journal-title":"Cancer Lett."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"283","DOI":"10.3892\/br.2016.720","article-title":"Potential role of bromelain in clinical and therapeutic applications","volume":"5","author":"Rathnavelu","year":"2016","journal-title":"Biomed. Rep."},{"key":"ref_11","first-page":"46","article-title":"Black Pepper: Overview of Health Benefits","volume":"45","author":"Singletary","year":"2010","journal-title":"Nutr. Today"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"645","DOI":"10.1124\/jpet.102.034728","article-title":"Piperine, a major constituent of black pepper, inhibits human P-glycoprotein and CYP3A4","volume":"302","author":"Bhardwaj","year":"2002","journal-title":"Int. J. Pharmacol. Exp. Ther."},{"key":"ref_13","first-page":"23","article-title":"Therapeutic effect of bromelain and papain on intestinal injury induced by indomethacin in male rats","volume":"17","author":"Madkhali","year":"2023","journal-title":"Int. J. Health Sci."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"116498","DOI":"10.1016\/j.carbpol.2020.116498","article-title":"Immobilization of papain enzyme on a hybrid support containing zinc oxide nanoparticles and chitosan for clinical applications","volume":"243","author":"Soares","year":"2020","journal-title":"Carbohydr. Polym."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"699","DOI":"10.1007\/s10815-015-0466-6","article-title":"Systemic oxidative stress could predict assisted reproductive technique outcome","volume":"32","author":"Ahelik","year":"2015","journal-title":"J. Assist. Reprod. Genet."},{"key":"ref_16","first-page":"210","article-title":"A new method to assess oxidative stress in ART cycles","volume":"6","author":"Albani","year":"2016","journal-title":"Gynecol. Endocrinol."},{"key":"ref_17","first-page":"277","article-title":"In Vitro Fertilization, Levels of Pro-Inflammatory Factors and Lipid Peroxidation","volume":"9","author":"Yildizfer","year":"2015","journal-title":"Int. J. Fertil. Steril."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"3003","DOI":"10.2174\/138161209789058110","article-title":"An update of the oxidation-inflammation theory of aging: The involvement of the immune system in oxi-inflamm-aging","volume":"15","author":"Miquel","year":"2009","journal-title":"Curr. Pharm. Des."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Lam, P., Cheung, F., Tan, H.Y., Wang, N., Yuen, M.F., and Feng, Y. (2016). Hepatoprotective Effects of Chinese Medicinal Herbs: A Focus on Anti-Inflammatory and Anti-Oxidative Activities. Int. J. Mol. Sci., 17.","DOI":"10.3390\/ijms17040465"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"30","DOI":"10.4103\/1735-1995.202151","article-title":"A review of plant-based compounds and medicinal plants effective on atherosclerosis","volume":"22","author":"Sedighi","year":"2017","journal-title":"J. Res. Med. Sci."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1016\/j.phrs.2016.03.026","article-title":"Curcumin downregulates human tumor necrosis factor-\u03b1 levels: A systematic review and meta-analysis of randomized controlled trials","volume":"107","author":"Sahebkar","year":"2016","journal-title":"Pharmacol. Res."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"918089","DOI":"10.1155\/2015\/918089","article-title":"The combination of N-acetyl cysteine, alpha-lipoic acid, and bromelain shows high anti-inflammatory properties in novel in vivo and in vitro models of endometriosis","volume":"2015","author":"Agostinis","year":"2015","journal-title":"Mediators Inflamm."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1055\/s-2006-957450","article-title":"Influence of piperine on the pharmacokinetics of curcumin in animals and human volunteers","volume":"64","author":"Shoba","year":"1998","journal-title":"Planta Med."}],"container-title":["Medicina"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1648-9144\/60\/2\/204\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T13:48:58Z","timestamp":1760104138000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1648-9144\/60\/2\/204"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,1,25]]},"references-count":23,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2024,2]]}},"alternative-id":["medicina60020204"],"URL":"https:\/\/doi.org\/10.3390\/medicina60020204","relation":{},"ISSN":["1648-9144"],"issn-type":[{"type":"electronic","value":"1648-9144"}],"subject":[],"published":{"date-parts":[[2024,1,25]]}}}