Mechanistic insights into the potential role of botanical drugs and plant-derived metabolites in mitigating oxidative stress in varicocele.

Authors

Anmin Wang, Elena Colonnello, Dongyue Ma, Hongyuan Chang, Hao Wang, Hui Lv, Di Sun, Haoyu Zhang, Wenxiao Yu, Fu Wang

Published in

Frontiers in pharmacology. Volume 17. Pages 1720260. Epub Sep 28, 2026.

Abstract

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 in vivo 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-Nrf2-ARE/HO-1, PI3K-Akt, MAPK/JNK-p38, HIF-1-related 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 in silico 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.

PMID:
42865606
Bibliographic data and abstract were imported from PubMed on 13 Oct 2026.

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