Icariin: from preclinical promise to clinical reality-a critical evidence-based assessment

Icariin (ICA), the principal flavonoid from Epimedii Folium, aligns with traditional Chinese medicine indications of tonifying kidney-yang and strengthening bone. Prior reviews mostly catalog ICA's preclinical neuroprotective, anti-fibrotic, anti-tumor, and osteoprotective effects, but lack evidence stratification. Here, we establish an evidence-stratified framework to evaluate ICA's structure-activity relationships, pharmacokinetics, and safety profiles, explicitly distinguishing preclinical pharmacological actions from unproven clinical efficacy. We delineate translational barriers including interspecies pharmacokinetic gaps, poor bioavailability, and flawed trial designs, and assess delivery systems to address these limitations. This work bridges traditional Chinese medicine practice with graded modern evidence, providing a translational roadmap to guide ICA's rational clinical development.