Beneficial effect of laserpitin, a coumarin compound from Angelica keiskei, on lipid metabolism in stroke-prone spontaneously hypertensive rats

Recently, we found that 4-hydroxyderricin, one of the major chalcones in Angelica keiskei extract (an ethyl acetate extract from the yellow liquid of stems), suppressed increases in systolic blood pressure and reduced both serum very low-density lipoprotein levels and liver triglyceride content in stroke-prone spontaneously hypertensive rats (SHRSP). In the present study, we have isolated laserpitin, a characteristic coumarin, from the A. keiskei extract and examined the effect of dietary laserpitin on blood pressure and lipid metabolism in SHRSP. Six-week-old male SHRSP were fed diets containing 0.1% laserpitin for 7 weeks with free access to the diet and water. Bodyweight gain was reduced by dietary laserpitin after 4 weeks through to 7 weeks without any significant change in daily food intake. Serum total cholesterol, phospholipid and apolipoprotein (apo) E levels were significantly increased, which was due to significant increases in cholesterol, phospholipid and apoE contents in the low- and high-density lipoprotein (LDL and HDL, respectively) fractions. These results suggest that dietary laserpitin increases serum apoE-HDL levels. In the liver, significant decreases in relative liver weight and triglyceride content were found after treatment with laserpitin for 7 weeks. An investigation of hepatic mRNA expression of proteins involved in lipid metabolism indicated that a significant decrease in hepatic triglyceride lipase may be responsible for the increase in serum HDL levels and also indicated that a marked decrease in adipocyte determination and differentiation factor 1 may be responsible, at least in part, for the decrease in hepatic triglyceride content. In conclusion, dietary laserpitin produces increases in serum HDL levels, especially apoE-HDL, and decreases in the hepatic triglyceride content in SHRSP.