Hypolipidemic Effect of Hexane Fraction from Rhizopus oryzae KSD-815 through Peroxisome Proliferator-Activated Receptor-α

Peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcriptional factors that belong to nuclear receptors superfamily and are involved in the regulation of lipid metabolism. In the present study, anti-hyperlipidemic properties of n-hexane fraction (RoHe) from cultures of Rhizopus oryzae KSD-815 (R. oryzae KSD-815), which was isolated from Nuruk, were studied. n-Hexane fraction lowered plasma low-density lipoprotein levels and total cholesterol in high cholesterol diet-fed rats, and showed comparable potency compared with that of gemfibrozil. n-Hexane fraction was further fractionated with hexane in increasing EtOAc gradient using cell-based transactivation assay for PPAR-alpha. The active subfraction 4 (3 g) was applied to octadecyl silica gel column chromatography (phi 4x4.5 cm) and eluted with MeCN-H2O (3:1, 1.8 L) to provide 14 fractions (RoHe-4-1 to RoHe -4-14). Results showed the 2nd-subfractions, RoHe-4-2 and RoHe-4-6 could activate PPAR-alpha and PPAR-gamma in a dose-dependent manner, and concentrations of fractions RoHe-4-2 and 4-6 to achieve half of GW409544 activity were 12.39 and 13.99 mg/mL, respectively. In functional assay using human hepatoma HepG2 cells, RoHe-4-2 and 4-6 significantly increased apolipoprotein A1 (ApoA1) production and showed more potent stimulation effects compared with fenofibrate. These results indicate that culture of R. oryzae KSD-815 may have a potent hypolipidemic activity through activation of PPAR-a and secretion of ApoA1.