The antioxidant and antiatherogenic effects of MAK-4 in WHHL rabbits

Oxidized low-density lipoprotein (ox-LDL) plays an important role in atherogenesis. Atheroma formation is reduced significantly in Watanabe heritable hyperlipidemic (WHHL) rabbits by antioxidants such as probucol and vitamin E. The herbal mixture Maharishi Amrit Kalash-4 (MAK-4) inhibits Cu+2 -induced LDL oxidation, and enzymatic- and nonenzymatic-induced microsomal lipid peroxidation. We tested the effect of MAK-4 on the development of atheroma in WHHL rabbits. Eleven rabbits were divided into two groups: controls (n = 5) and a group fed 6% (w/w) MAK-4 (n = 6). Blood was drawn for biochemical analysis every two months and at necropsy, six months after the special diet was started. The aortas were preserved in formalin. The percentage area of aortic arch covered with visible plaque in the MAK-4 group (22.5 +/- 4.2%, mean +/- SE) was significantly reduced (p < 0.01) compared to the control group (47.6 +/- 6.8%, mean +/- SE). The MAK-4 group showed a significant decrease (p < 0.05) in lipid peroxide, and a significant increase (p < 0.05) in glutathione peroxidase and resistance of LDL to endothelial cell-induced and cupric ion-catalyzed oxidation (4.5 h and 5 h lag phase, respectively, for the MAK-4 group; 0 h lag phase for both for the controls). These findings suggest MAK-4 reduces atheroma formation through its antioxidant activity.