Inhibitory effects of perillosides A and C, and related monoterpene glucosides on aldose reductase and their structure-activity relationships.

Monoterpene glucosides, perillosides A and C, obtained from the leaves of Perilla frutescens, were found to be inhibitors of aldose reductase (EC 1.1.1.21) which is considered to be a key enzyme in diabetic complications such as cataract. The apparent type of inhibition of rat lens aldose reductase by perillosides A and C was competitive with respect to glyceraldehyde and their K(i) values were 1.4 x 10(-4) and 2.3 x 10(-4) M, respectively. The type of inhibition by their tetraacetates was non-competitive with respect to the same substrate, although their inhibitory effects were increased by about one order of magnitude compared with those of the perilllosides and the K(i) values were 2.5 x 10(-5) and 7.1 x 10(-5) M, respectively. We also prepared related monoterpene glucosides and their tetraacetates and determined their inhibitory activities towards aldose reductase in order to elucidate the relationship between structure and inhibitory activity.