|Budget Amount *help
¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 1996: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 1995: ¥700,000 (Direct Cost: ¥700,000)
Effects of lignan compounds on lipid metabolism were investigated in hyperlipidemic stroke-prone SHR (SHRSP) fed a high-fat and high-cholesterol diet (HFC diet). Lipid-regulating drugs using for clinical treatment were also tested to compare the efficacy.
The results are as follows : 1) Sesamin mixture [a mixture of sesamin and episesamin, 0.5% addition to the control diet (HFC diet)] significantly suppressed an increase in serum total cholesterol. This was due mainly to suppression of an increase in atherogenic beta-VLDL,which was associated with suppression of a decrease in anti-atherogenic HDL rich in apoA-I.In addition, hepatic cholesterol accumulation was significantly suppressed. Finally, it is suggested that episesamin, one of diastereomers of sesamin, may contribute to these effective actions. Moreover, the actions seemed to be similar to those of gemfibrozil (Lopid). 2) Tochu leaf, containing lignan compounds abundantly, suppressed both elevation of total serum cholesterol and accumulation of hepatic cholesterol. These results strongly suggest that lignan compounds may improve lipid metabolism.
Next, to elucidate mechanism of the effective actions, effects of isolated natural compounds such as lignans, iridoids, flavonoids and others on the activity of HMG-CoA reductase, which is the rate-limiting enzyme of cholesterol biosynthesis, were examined in the human hepatoma cell line, Hep G2.
Among tested natural compounds, quercetin glycosides and geniposidic acid expressed inhibitory activity, while lignan compounds not so evident. These results indicated that the effect of lignan compounds may not be due to HMG-CoA reductase inhibition, and there may be close relationship between structure of compound and inhibitory activity.