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

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, sexualreproduction,andprotectionagainstharmfuleffectsontheheart,brain,bones,lungs,kidneys,livers,andeyes.Molecularmechanismsofactionwerededucedfromvarioussignalingpathways,suchasAkt/NOS/NF-κB, JAK/STAT3/MAPK, and PI3K/Akt/mTOR. Pharmacokinetic evidence involved sugar and methyl removals, hydroxylation,glucuronidation,andglycosylation.