Epimedium: Medicinal plant resources, chemical constituents, pharmacological actions, and biosynthesis of prenylated flavonol glycosides

Epimedii Folium ( Epimedium ) is a valuable Chinese medicinal material that has long been used clinically and exhibits diverse pharmacological activities. With research on Epimedium growing rapidly, a comprehensive review integrating its taxonomy, medicinal resources, chemical constituents, pharmacological effects, and biosynthesis is urgently needed. This review comprehensively summarizes the taxonomy, resource distribution, chemical composition, and pharmacological activities of Epimedium , with particular emphasis on the complex biosynthetic pathways and regulatory mechanisms of prenylated flavonol glycosides (PFGs). Medicinal Epimedium species include Epimedium brevicornu, Epimedium pubescens, Epimedium sagittatum, Epimedium koreanum, and Epimedium wushanense. Among them, E. koreanum is uniquely distributed in Northeastern China, while the other four have overlapping habitats. Epimedium shares a rich chemical composition, including flavonoids, lignans, and polysaccharides. PFGs, such as icariin (ICA), are the most characteristic active constituents of Epimedium and are closely associated with its major pharmacological activities, including kidney-tonifying, antitumor, and neuroprotective effects. The complete biosynthetic pathways of ICA and its derivatives starting from phenylalanine were reviewed for the first time. The structural genes that encode key enzymes, such as phenylalanine ammonia-lyase, O-methyltransferase, and UDP-glycosyltransferase, in the biosynthesis were characterized. The biosynthetic pathway is primarily regulated by MYB transcription factors and environmental factors such as light, humidity, and soil conditions. This review provides a comprehensive overview of Epimedium , with particular emphasis on the first full-pathway analysis of ICA biosynthesis and its regulation, and offers a theoretical basis for the conservation and sustainable utilization of Epimedium resources. • Epimedium , a traditional Chinese medicine, has multiple plant sources and is widely distributed. • Prenylated flavonol glycosides are the active components of Epimedium , exhibiting antitumor and other pharmacological effects. • The complete biosynthetic pathway and key enzyme genes of icariin and its derivatives were analyzed. • The transcription factors and environmental factors regulating the biosynthesis were introduced.