Advances in Extraction, Purification, and Pharmacological Mechanisms of Calycosin: A Comprehensive Review

Calycosin, a pivotal isoflavonoid active constituent derived from Astragalus membranaceus, is designated as a key marker compound for the quality assessment of Astragalus and its products in the Pharmacopoeia of the People's Republic of China (2020 Edition). It exhibits a broad spectrum of pharmacological activities and holds significant potential for clinical application. This article provides a systematic review of its research progress: In terms of extraction, isolation, and purification, techniques such as flash extraction and hydrolytic extraction enable efficient enrichment of this compound, while methods like macroporous adsorption resin and high-speed counter-current chromatography allow for high-purity preparation. Its biosynthetic pathways encompass the phenylpropanoid pathway in planta, the chemical "one-pot" method in vitro, and synthesis via microbial cell factories, offering diverse strategies for large-scale production. Structural derivatization, particularly through modification of the 7- and 3'-hydroxyl groups, has been shown to significantly enhance its solubility and antitumor activity. Regarding pharmacological mechanisms, calycosin exerts multi-pathway and low-toxicity effects in diseases such as inflammation, cancer, and neural injury by modulating multiple signaling pathways, including NF-κB, PI3K/AKT, and MAPK. Furthermore, pharmacokinetic studies indicate that its absorption depends on deglycosylation conversion, it undergoes significant hepatic first-pass metabolism, and its tissue distribution is organ-specific. Safety evaluations suggest low toxicity at therapeutic concentrations. This review aims to clarify the core issues concerning the translation of its basic research into clinical practice, thereby providing a theoretical foundation for subsequent development.