Effect Of Momordicin On Foam Formation Of Human THP-1 Derived Macrophage

The accumulation of neutral lipid,such as cholesterol ester, plays a key role in the foam-cell formation and in the development of atherosclerotic lesions. There are some important factors relating to the formation of foam cell. It's known that acyl-coenzyme A:cholesterol acyltransferase (ACAT) is the main intracellular cholesterol ester synthetase .It catalyzes free cholesterol and long-chain fatty acid to synthesize cholesterol ester so that it is implicated in the formation of foam cells and influence the development of atherosclerosis. We have researched momordicin extracted from momordica charantia L for many years. Momordicin have effects of lowering the rate of blood fat and glucose, antiinflamation and antioxygen, and so on. Recently we have found that momordicin have some effect on rejecting the lesion of atherosclerosis, but the exact mechanism is not clear yet now. In view of the above knowledge, this study is to explore whether and how momordicin affect the formation of THP-1 foam cells, how momordicin affect foam cells, at last to explore the influence of momordicin on the expression of ACAT1.Objective To explore whether and how momordicin affect the formation of THP-1 foam cells ,whether momordicin could reverse foam cells somewhat, and to study the potential mechanism.Methods The extraction of momordicin from momordica charantia L was according to Wang's methods. THP-1cells were incubated with ox-LDL and or not and momordicin of different doses for 48h. The intracellular lipid droplets was observed with oil red O staining. The level of intracellular cholesterol and cholesterol efflux were determined by high performance liquid chromatography (HPLC). The protein expression of ACAT1 was revealed by Western blot.Results THP-1 cells were incubated with ox-LDL and with or without momordicin of different doses for 48 hours.By oil red O staining ,we found that the intracellular droplets of cells treated with momordicin were smaller and fewer than cells with ox-LDL only. And as the momordicin doses went up, the difference was becoming more obviously. The total cholesterol(TC), cholesterol ester(CE), CE/TC of cells with momordicin were lower much than those only with ox-LDL by high performance liquid chromatography analysis. THP-1 foam cells were incubated with momodicin for different times after incubated with only ox-LDL for 48 hours. With oil red O staining, we found that the intracellular lipid droplets of foam cells treated with momordicin after were much fewer and smaller than those foam cells not treated with momordicin. Some efflux and decreace of lipid droplets was also found from foam cells after treated with momordicin. Western blot demonstrated that the expression of ACAT1 protein on cells treated with momordicin was lower than that on cells treated only with ox-LDL.Conclusions Momordicin inhibit the foam formation of THP-1 derived macrophage and decreace the lipid contents of THP-1 derived foam cells. ACAT1 protein expression of THP-1 foam cells could be downregulated by momordicin.