해방풍의 프로스타그란딘 E2증가와 지질 개선 효과

Abstract

Ischemic heart diseases and stroke are major causes of death in Korea. Their risk factors include dyslipemia, hypertension, diabetes mellitus, smoking, family history and so on. Many drugs and natural plants have been applied for prophylaxis and treatment of them. Of them, Glehnia littoralis (Haebangpoog in Korean) has calcium channel blocking, anticoagulatory, anticonvulsive, antioxidant and antiinflammatory effects, which is literally known to be effective in stroke. As potential mechanisms of this, effects of Glehnia littoralis on prostaglandin E2 and lipid metabolism were investigated in this study. Cytotoxicity was determined by MTT assay. For assay of inhibitory activity of 15-prostaglandin dehydrogenase (15-PGDH), NADH formation was detected by fluorescence spectrophotometer. And PGE2 was determined by enzyme immunoassay in HaCaT cells. mRNA expressions of specific genes were analyzed by RT-PCR assay. In vitro scratch test was done using in HaCaT cells. Dual luciferase reporter assay was performed for the activation of PPARr. HMG-CoA reductase activity was determined using the assay kit. Glehnia littoralis root extracts showed differential 50 % inhibitory concentration (IC50) of 15-PGDH (13.0 µg/mL ~ 393.1 µg/mL according to solvents). Glehnia littoralis leaf extracts also showed various IC50 values (1.7 µg/mL ~ > 500 µg/mL according to solvents). Among them, Glehnia littoralis leaf ethyl acetate extract (GLEA) showed the strongest 15-PGDH inhibitory activity (IC50, 1.7 µg/mL). It also down-regulated 15-PGDH mRNA expression without effects on those of genes influencing on PGE2 fate. In addition, GLEA (50 µg/mL) showed wound healing effect comparable with that obtained with TGF-β1 (100 pg/mL). GLEA (50 µg/mL) decreased the ratio of ApoB100/A-1 by 84.4% of the control in HepG2 cells. In addition, GLEA inhibited the activity (IC50, 635.8 µg/mL) of HMG-CoA reductase, a rate limiting enzyme of cholesterol synthesis. Moreover, GLEA up-regulated mRNA expression of PPARr with activation of PPARr. Taken together, GLEA can increase PGE2 level by inhibiting its inactivating enzyme 15-PGDH. Also, it decreases ApoB100/ApoA-1 ratio, inhibits HMG-CoA reductase activity and activates PPARr. It is thus implicated that Glehnia littoralis could increase blood flow and decrease peripheral resistance, resulting in positive effects on ischemic heart disease and stroke.