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Although their protective role in stressed testicular cells is established, their impact on Leydig cell steroidogenesis under non-pathological conditions remains poorly understood. Here, we investigated how an anthocyanin-enriched fraction from Callistemon citrinus (0\u20131.00 \u03bcg\/mL) affects androgen synthesis in murine TM3 Leydig cells. Cell viability, intracellular ROS, antioxidant capacity, mitochondrial function, androstenedione production, steroidogenic gene expression, and the exometabolome by 1H-NMR were assessed. The fraction exhibited biphasic, dose-dependent effects. At 0.01 \u03bcg\/mL, it induced a mitohormetic response, upregulating mitochondrial complexes III and V. Conversely, higher concentrations (0.10\u20131.00 \u03bcg\/mL) reduced metabolic activity, increased intracellular ROS, and significantly suppressed androstenedione synthesis independently of Star. These concentrations also induced dose-dependent repression of Cyp17a1, concomitant with upregulation of Nr0b2, encoding the transcriptional repressor Small Heterodimer Partner (SHP). Overall, the data support a redox-dependent mechanism whereby elevated ROS promotes Nr0b2 expression, leading to Cyp17a1 suppression and impaired androstenedione production. These findings challenge the view of anthocyanins as uniformly beneficial for male fertility and identify Callistemon citrinus as a sustainable source of bioactive anthocyanins capable of modulating redox\u2013endocrine homeostasis in a dose-dependent manner under basal conditions.<\/jats:p>","DOI":"10.3390\/antiox15050530","type":"journal-article","created":{"date-parts":[[2026,4,23]],"date-time":"2026-04-23T08:11:14Z","timestamp":1776931874000},"page":"530","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Pro-Oxidant Anthocyanins-Enriched Fraction Inhibits Androgen Synthesis by Transcriptional Repression of Cyp17a1 Through Nr0b2"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-0792-5895","authenticated-orcid":false,"given":"Giuseppe T.","family":"Patan\u00e8","sequence":"first","affiliation":[{"name":"Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, 98166 Messina, Italy"},{"name":"Prof. Antonio Imbesi Foundation, University of Messina, 98100 Messina, Italy"},{"name":"Institute of Biomedicine, Department of Medical Sciences (iBiMED), University of Aveiro, 3810-193 Aveiro, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-9130-5809","authenticated-orcid":false,"given":"Ruben J.","family":"Moreira","sequence":"additional","affiliation":[{"name":"Institute of Biomedicine, Department of Medical Sciences (iBiMED), University of Aveiro, 3810-193 Aveiro, Portugal"},{"name":"Associated Laboratory for Green Chemistry of the Network of Chemistry and Technology (LAQV-REQUIMTE), Department of Chemistry, University of Aveiro, 3810-193 Aveiro, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7261-9596","authenticated-orcid":false,"given":"Ana D.","family":"Martins","sequence":"additional","affiliation":[{"name":"Associated Laboratory for Green Chemistry of the Network of Chemistry and Technology (LAQV-REQUIMTE), Department of Chemistry, University of Aveiro, 3810-193 Aveiro, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4989-5699","authenticated-orcid":false,"given":"Pedro F.","family":"Oliveira","sequence":"additional","affiliation":[{"name":"Associated Laboratory for Green Chemistry of the Network of Chemistry and Technology (LAQV-REQUIMTE), Department of Chemistry, University of Aveiro, 3810-193 Aveiro, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefano","family":"Putaggio","sequence":"additional","affiliation":[{"name":"Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, 98166 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1463-4069","authenticated-orcid":false,"given":"Davide","family":"Barreca","sequence":"additional","affiliation":[{"name":"Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, 98166 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7635-783X","authenticated-orcid":false,"given":"Marco G.","family":"Alves","sequence":"additional","affiliation":[{"name":"Institute of Biomedicine, Department of Medical Sciences (iBiMED), University of Aveiro, 3810-193 Aveiro, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1016\/j.clinbiochem.2018.03.012","article-title":"Fertility and infertility: Definition and epidemiology","volume":"62","author":"Wyns","year":"2018","journal-title":"Clin. 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