{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T05:57:17Z","timestamp":1790575037113,"version":"4.1.0"},"reference-count":154,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T00:00:00Z","timestamp":1790553600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:p>\n                    Varicocele (VC) is a prevalent male urogenital disorder associated with scrotal discomfort, impaired semen quality, and endocrine dysregulation, in which oxidative stress (OS) is repeatedly implicated as a key pathogenic axis linking venous stasis, hypoxia, hyperthermia, inflammation, mitochondrial dysfunction, and germ-cell injury. This review critically evaluates experimental and clinical evidence on defined botanical drugs and plant-derived metabolites investigated in VC or VC-relevant OS models, with an emphasis on mechanistic plausibility and translational limitations. Across\n                    <jats:italic>in vivo<\/jats:italic>\n                    VC models, toxin-\/heat-\/hypoxia-induced spermatogenic injury models, and selected clinical studies, multiple interventions have been reported to improve semen parameters, testicular histology, and redox indices (e.g., ROS, MDA, SOD\/CAT\/GPx, GSH\/GSSG), alongside modulation of apoptosis and stress responses. Reported molecular nodes converge on redox- and stress-responsive pathways, including Keap1\u2013Nrf2\u2013ARE\/HO-1, PI3K\u2013Akt, MAPK\/JNK\u2013p38, HIF-1\u2013related signaling, ER-stress responses, mitochondrial apoptosis (e.g., Bax\/Bcl-2\/caspases), and, in some models, ferroptosis-related regulation. However, the overall evidence base is constrained by heterogeneity in models and endpoints, limited extract\/compound chemical characterization and pharmacological standardization, frequent reliance on\n                    <jats:italic>in silico<\/jats:italic>\n                    predictions, small or non-randomized clinical cohorts, and incomplete reporting of taxonomic and product quality details. Future work should prioritize rigorously designed, adequately powered clinical trials with standardized outcomes, well-defined interventions, and mechanism-aligned biomarkers to clarify which botanical drugs\/metabolites offer clinically meaningful benefit as adjuncts in VC management.\n                  <\/jats:p>","DOI":"10.3389\/fphar.2026.1720260","type":"journal-article","created":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T05:44:47Z","timestamp":1790574287000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Mechanistic insights into the potential role of botanical drugs and plant-derived metabolites in mitigating oxidative stress in varicocele"],"prefix":"10.3389","volume":"17","author":[{"given":"Anmin","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Andrology, Xiyuan Hospital of China Academy of Chinese Medical Sciences","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Colonnello","sequence":"additional","affiliation":[{"name":"Endocrinology and Medical Sexology (ENDOSEX), Department of Systems Medicine, University of Rome Tor Vergata","place":["Rome, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongyue","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Andrology, Xiyuan Hospital of Clinical Medical College of Beijing University of Chinese Medicine","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongyuan","family":"Chang","sequence":"additional","affiliation":[{"name":"Department of Andrology, Xiyuan Hospital of China Academy of Chinese Medical Sciences","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Andrology, Xiyuan Hospital of China Academy of Chinese Medical Sciences","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Lv","sequence":"additional","affiliation":[{"name":"Department of Andrology, Xiyuan Hospital of China Academy of Chinese Medical Sciences","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Di","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Andrology, Xiyuan Hospital of China Academy of Chinese Medical Sciences","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haoyu","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, Xiyuan Hospital of Clinical Medical College of Beijing University of Chinese Medicine","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenxiao","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Andrology, Xiyuan Hospital of China Academy of Chinese Medical Sciences","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fu","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Andrology, Xiyuan Hospital of China Academy of Chinese Medical Sciences","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,28]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"461","DOI":"10.1016\/j.urology.2008.07.053","article-title":"Role of oxidative stress in pathogenesis of varicocele and infertility","volume":"73","author":"Agarwal","year":"2009","journal-title":"Urology"},{"key":"B2","doi-asserted-by":"publisher","first-page":"678","DOI":"10.1038\/nrurol.2012.197","article-title":"Insight into oxidative stress in varicocele-associated Male infertility: part 1","volume":"9","author":"Agarwal","year":"2012","journal-title":"Nat. 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