Icariin, a major active constituent of Epimedium, promotes estrogen biosynthesis, and enhances aromatase mRNA and protein expression as well as alkaline phosphatase activity in vitro ⁽¹⁾. However, other studies have attributed estrogen-like activity to icariin derivatives icaritin and desmethylicaritin, rather than icariin itself ⁽¹⁴⁾. Icariin can also exhibit a mild phosphodiesterase-5 inhibition effect ⁽¹⁶⁾. It has been implicated in differentiation of stem cells into cardiomyocytes via cell cycle regulation, induction of apoptosis, modulation of reactive oxygen species generation, and the regulation of various signaling pathways ⁽¹⁷⁾. In undifferentiated neuronal cell lines, it exhibited neuroprotective effects through LDH leakage attenuation which reduced GSH depletion, prevented DNA oxidation damage, and inhibited caspase-3 and p53 activation; and inhibited JNK/p38 MAPK pathways ⁽⁴⁾. Icariin was also shown to reduce viability of  human esophageal cancer cells by regulating apoptotic signaling, which is mediated by endoplasmic reticulum stress ⁽²³⁾.

Icaritin, a prenylflavonoid derivative, induced sustained activation of extracellular signal-regulated kinase (ERK) pathway and apoptosis in both breast ⁽⁹⁾ and endometrial cancer cells ⁽¹⁸⁾. It also induced G2/M phase cell-cycle arrest and downregulated G2/M regulatory protein expression ⁽⁹⁾. Its radiosensitizing effects suggest ERK1/2 and AKT pathway suppression, enhanced apoptosis, and induced G2/M blockage ⁽¹¹⁾. Also, icaritin may reverse doxorubicin resistance in human hepatoma cells by increasing intracellular drug accumulation, and by decreasing MDR1 and P-glycoprotein expression ⁽¹²⁾. In another study, addition of an epimedium extract to gefitinib was shown effective against drug resistance caused by T790M mutation in non-samll cell lung cancer cells ⁽²⁴⁾.