Epimedium koreanum Extract and Its Flavonoids Reduced Atherosclerotic Risk via Suppressing Modification of Human HDL

Atherosclerosis is the key factor responsible for cardiovascular events, which is a major cause of morbidities and mortalities worldwide. It is well known that high-density lipoprotein (HDL) oxidation and glycation increases the risk for atherosclerosis. Epimedium koreanum has been used as a traditional oriental medicine for treating erectile dysfunction, kidney diseases, osteoporosis, and breast cancer. However, no reports on the effects of E. koreanum on HDL modification exist. In this study, we investigated the inhibitory effects of E. koreanum extract and its eight flavonoids, which are: (1) anhydroicaritin 3-O-rhamnoside, (2) β-anhydroicaritin, (3–5) epimedins A-C, (6) epimedoside A, (7) icariin, and (8) des-O-methyl-β-anhydroicaritin, against HDL modification. HDLs obtained from pooled human plasma samples were incubated in vitro with E. koreanum extract or each compound in the presence of copper sulfate or fructose. The HDL modifications were evaluated by measuring generation of conjugated dienes, production of thiobarbituric acid reactive substances, change in electrophoretic mobility of apoA-I, advanced glycation end products formation, and apoA-I aggregation. Consequently, E. koreanum extract and compound 8 suppressed HDL modification through inhibition of lipid peroxidation, apoA-I aggregation, negative charge increase, and AGEs formation. In particular, compound 8 showed more potent inhibitory effect on HDL modification than the extracts, suggesting its protective role against atherosclerosis via inhibition of HDL oxidation and glycation.