Icariside II: natural occurrence, biotransformation, pharmacological activity, synthetic modification, pharmacokinetics, and bioavailability

Abstract Objectives Icariside II (ICS-II), a flavone containing 3-rhamnopyranosyl and 8-prenyl groups, is one of the main natural compounds found in Epimedum species (the family Berberidaceae). The current study aims to provide a systematic review of its natural occurrence, pharmacological value, synthetic modification, pharmacokinetics, and bioavailability. Key findings Sources such as Google Scholar, Web of Science, PubMed, and journal websites were used to gather references about ICS-II. ‘Icariside II’ is the most meaningful keyword to seek references, and references have been updated till now. Summary ICS-II is a characteristic metabolite of various Epimedum plants, and it can be obtained by enzymatic hydrolysis of other flavonoids. It is a promising compound with multiple in vitro and in vivo pharmacological potentials. The studied flavone showed cancer-related biological activity via cell cycle arrest, proliferation inhibition, autophagy, and apoptosis and inhibited cytokines in anti-inflammatory actions. Significantly, the health benefits were accompanied by its role in antidiabetics, sexual reproduction, and protection against harmful effects on the heart, brain, bones, lungs, kidneys, livers, and eyes. Molecular mechanisms of action were deduced from various signaling pathways, such as Akt/NOS/NF-κB, JAK/STAT3/MAPK, and PI3K/Akt/mTOR. Pharmacokinetic evidence involved sugar and methyl removals, hydroxylation, glucuronidation, and glycosylation.