Berberine is identified to lower the serum cholesterol level in human and hamster through the induction of low density lipoproteins （LDL） receptor in hepatic cells. To evaluate its potential in preventing atheroscle...Berberine is identified to lower the serum cholesterol level in human and hamster through the induction of low density lipoproteins （LDL） receptor in hepatic cells. To evaluate its potential in preventing atherosclerosis, the effect of berberine on atherosclerosis development in apolipoprotcin E-deficient （apoE^-/-） mice was investigated. In apoE^-/- mice, berberine induced in rivo foam cell formation and promoted atheroselerosis development. The foam cell formation induced by berberinc was also observed in mouse RAW264.7 cells, as well as in mouse and human primary macrophages. By inducing scavenger receptor A （SR-A） expression in macrophages, berberine increased the uptake of modified LDL （DiO-Ac-LDL）. Bcrberine-induced SR-A expression was also observed in macrophage foam cells in vivo and in the cells at atherosclerotic lesion. Analysis in RAW264.7 cells indicated that berberine induced SR-A expression by suppressing PTEN expression, which led to sustained Akt activation. Our results suggest that to evaluate the potential of a cholesterol-reducing compound in alleviating atherosclerosis, its effect on the ceils involved in atherosclerosis development, such as macrophages, should also be considered. Promotion of foam cell formation could counter-balance the beneficial effect of lowering serum cholesterol.展开更多
文摘Berberine is identified to lower the serum cholesterol level in human and hamster through the induction of low density lipoproteins （LDL） receptor in hepatic cells. To evaluate its potential in preventing atherosclerosis, the effect of berberine on atherosclerosis development in apolipoprotcin E-deficient （apoE^-/-） mice was investigated. In apoE^-/- mice, berberine induced in rivo foam cell formation and promoted atheroselerosis development. The foam cell formation induced by berberinc was also observed in mouse RAW264.7 cells, as well as in mouse and human primary macrophages. By inducing scavenger receptor A （SR-A） expression in macrophages, berberine increased the uptake of modified LDL （DiO-Ac-LDL）. Bcrberine-induced SR-A expression was also observed in macrophage foam cells in vivo and in the cells at atherosclerotic lesion. Analysis in RAW264.7 cells indicated that berberine induced SR-A expression by suppressing PTEN expression, which led to sustained Akt activation. Our results suggest that to evaluate the potential of a cholesterol-reducing compound in alleviating atherosclerosis, its effect on the ceils involved in atherosclerosis development, such as macrophages, should also be considered. Promotion of foam cell formation could counter-balance the beneficial effect of lowering serum cholesterol.
