Galloyl Esters from Rhubarb are Potent Inhibitors of Squalene Epoxidase, a Key Enzyme in Cholesterol Biosynthesis

Galloyl glucoses and galloyl proanthocyanidins obtained from rhubarb (Rhei Rhizoma, Rheum palmatum L., Polygonaceae); e.g. 1,2,6-tri-O-galloyl-beta-D-glucose (IC50 = 0.63 microM), 1,6-di-O-galloyl-2-O-cinnamoyl-beta-D-glucose (IC50 = 0.58 microM), procyanidin B-2 3,3'-di-O-gallate (IC50 = 0.54 microM), and procyanidin B-5 3,3'-di-O-gallate (IC50 = 0.55 microM), were found to be potent inhibitors of rat squalene epoxidase (SE). The inhibition at submicromolar level was far more potent than that of chemically synthesized substrate analogs. It was demonstrated for the first time that the cholesterol-lowering effect of rhubarb may be attributed to the potent inhibition activities of SE, a rate-limiting enzyme of cholesterol biogenesis.