Icariin in male reproduction: Multi-target pharmacological mechanisms and therapeutic potential

Epimedium (Berberidaceae) is a fundamental herb in traditional Chinese medicine, historically prescribed for Kidney deficiency syndromes manifesting as reproductive decline and age-related debility. Its classic function of tonifying the Kidney and invigorating the Yang is supported by a complex, multi-component pharmacological profile. It is a cornerstone of traditional Chinese medicine and the 'monarch' drug in classical formulas like Er-xian Tang. As the most abundant and systematically studied active monomer in Epimedium extracts, ICA combines the antioxidant backbone of flavonoids with the biological membrane affinity conferred by its isoprene side chain. This dual nature enables it to exhibit potent biological activity and signaling regulation capabilities across diverse tissues. In recent years, ICA's regulatory role in male reproductive physiology has garnered increasing attention. It can significantly improve male reproductive function by regulating redox homeostasis, hormonal biosynthesis, and the balance between apoptosis and proliferation. It may also be used in combination with pharmacological agents or biotechnological approaches to enhance therapeutic efficacy further. Therefore, this review systematically examines the targets and mechanisms through which ICA improves male reproductive function and evaluates its value as monotherapy or as a component of combination therapies, providing a theoretical framework and translational research direction for managing male reproductive disorders and enhancing assisted reproductive technologies outcomes.