백수오, 우엉, 마 추출물 혼합비율에 따른 혈관부착인자 VCAM-1의 발현억제 효과
Suppression of VCAM-1 Expression in Human Aortic Smooth Muscle Cells Treated with Ethanol Extracts of Cynanchum wilfordii Radix, Arctium lappa L., and Dioscorea opposita
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본 연구에서는 혈관염증 억제 효능이 입증된 원료인 백수오, 우엉, 마를 혼합하여 혈관염증을 완화시키고 동맥경화의 발생위험을 줄일 수 있는 소재를 개발하기 위하여, 혼합물이 혈관염증을 가장 효과적으로 억제하는 배합비율을 찾아내고자 하였다. 백수오, 우엉, 마 단독투여 및 다양한 혼합비로 혼합물을 제조하여 인간유래 동맥 평활근 세포에 공급하였다. 세포부착인자인 VCAM-1의 mRNA 발현에 미치는 영향을 비교하여 가장강한 억제효과를 나타낸 CADM5 (백수오:우엉:마=2:1:1)을 선택하였다. 선택된 혼합물이 혈관세포에서 얼마나 독성을 나타내는지 실험하였고, 백수오, 우엉, 마 추출혼합물이 혈관염증에 관여된 단백질 발현에 미치는 영향을 측정하였다. CADM5처리 결과 염증으로 인하여 증가하였던 ICAM-1과 VCAM-1 단백질의 발현이 감소하였다. 또한 CADM5를 처리한 결과 혈관내피세포에서 산화적 손상 및 염증 방어와 관련이 있는 HO-1과Nrf-2의 발현이 증가되었다. 따라서 CADM5이 염증에 의해 유도된 ICAM-1 그리고 VCAM-1의 발현을 조절하고 산화스트레스의 방어기전을 활성화 함으로써 동맥경화증을 유발하는 혈관염증의 초기단계를 억제하여 항염증 작용에 효과가 있음을 기대할 수 있다. 비교적 저농도인 32 ㎍/㎖에서 효과적으로 혈관염증 관련 단백질 발현을 조절하였으므로 본 연구를 통해 선택된 CADM5의 혈관염증개선 및 혈관건강개선 소재로서의 개발가능성을 확인하였다.
Abstract
Cynanchum wilfordii Radix (CWR), Arctium lappa L (ALL), and Dioscorea opposite (DO) have been known to improve blood lipid profile, blood pressure, and inflammation. To find the optimal combination ratio of CWR, ALL, and DO in terms of vascular health improvement, we compared the effects of various combinations on gene expression of Vascular cell adhesion protein 1 (VCAM-1) in human aortic smooth muscle cells (HASMC). VCAM-1 mediates endothelial leukocyte adhesion and is upregulated in atherosclerosis. Cells was stimulated by TNF-α (10 ng/㎖, 2h) and treated with various combinations for 24 h. A combination (CADM5, CWR:ALL:DO = 2:1:1) showed the strongest suppression of VCAM-1 so that CADM5 was chosen for further experiments. We performed cell viability test with CADM5 (0, 3.125, 12.5, 25, 50, and 100 ㎍/㎖) and no cytotoxicity was found. We also investigated the effect of CADM5 on protein expression of VCAM-1, ICAM-1, Nrf-2, and HO-1 using western blotting. We found that CADM5 diminished the expression of VCAM-1 and increased the expression of Nrf-2 and HO-1. Therefore, we concluded that CADM5 (CWR:ALL:DO = 2:1:1) effectively improves vascular health by regulating the expression of VCAM-1. Key words - Cynanchum wilfordii Radix, Arctium lappa L, Dioscorea opposite, VCAM-1, HASMCs
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