Icariin, a Multi-Target Natural Neuroprotectant, and a Comprehensive Review on Its Synthetic Methods, Pharmacological Evaluation and Pharmacokinetic Characteristics

Epimedii Folium (Yinyanghuo), a unique and traditional Chinese medicinal plant used in medicine for more than a thousand years, has been traditionally used to tonify the liver and kidneys, strengthen the muscles and bones, and eliminate rheumatism. Its principal active ingredient, icariin, has long been used clinically for impotence and spermatorrhea, weakness of muscles and bones, rheumatism and arthralgia pain, and has recently attracted growing attention for its therapeutic potential against central nervous system diseases. This review summarizes advances over the past five years in the preparation, neuroprotective effects, and pharmacokinetics of icariin. The literature was retrieved from Pubmed, CNKI (China National Knowledge Infrastructure), Web of Science, and Google Scholar using keywords including “icariin”, “Epimedii Folium”, “neuroprotection”, “biosynthesis” and “pharmacokinetics”, and studies were screened for relevance to preparation methods, pharmacological evaluation, and pharmacokinetic properties. Although extraction from plant sources remains the main preparation method, chemical synthesis and biosynthesis are emerging in response to resource scarcity. Accumulating evidence indicates that icariin exerts neuroprotective effects through multiple mechanisms, including anti-neuroinflammation, mitochondrial protection, antioxidant effects, inhibition of neuronal apoptosis, promotion of neuronal proliferation and differentiation and regulation of synaptic plasticity. Its rapid absorption, ability to cross the blood–brain barrier, and low cumulative toxicity provide a favorable pharmacokinetic basis for central nervous system applications. This review highlights synthetic strategies, pharmacological evaluation and pharmacokinetic characteristics of icariin, aiming to support its broader application in CNSDs.