Magnolol, a potent antioxidant from Magnolia officinalis, attenuates intimal thickening and MCP-1 expression after balloon injury of the aorta in cholesterol-fed rabbits

Background: Restenosis is a common complication after balloon angioplasty. A number of cytokines, chemotactic factors and growth factors may be involved. Several antioxidants have been shown to inhibit intimal thickening after balloon injury in hyperlipidemic animals. Objectives: The effects of magnolol on the expression of monocyte chemotactic protein-1 (MCP-1) and intimal response in balloon injured aorta of cholesterol-fed rabbits were investigated. Methods: Male New Zealand white rabbits were fed a 2% high cholesterol (HC) diet together with daily intramuscular injection of either 1 μg/kg B.W. of magnolol (HC-M, n = 10) or vehicle (propylene glycol) as a control (HC-C, n = 10) for a total of 6 weeks. Another 10 rabbits fed a regular diet also served as a control (C) group. A balloon denudation of abdominal aorta was performed in each group at the end of the third week. The aortas were harvested at the end of 6 weeks. Results: Magnolol treatment significantly inhibited Cu²⁺-induced LDL oxidation in cholesterol-fed rabbits and reduced atheroma formation [atheroma area ratio: 0.10 ± 0.03 (HC-M) versus 0.33 ± 0.07 (HC-C), p < 0.05] in thoracic aortas without lowering serum cholesterol. The intimal response was significantly attenuated in the HC-M rabbits when compared to those of the HC-C group [intimal thickness: 88.95 ± 14.91 μm (HC-M) versus 198.02 ± 20.35 μm (HC-C), p < 0.05; intimal area: 278.21 ± 43.16 × 10³ μm² (HC-M) versus 642.70 ± 65.01 × 10³ μm² (HC-C), p< 0.05]. The MCP-1 mRNA and protein expression were reduced in the HC-M group compared to the HC-C and C groups. Conclusion: The inhibitory effects on intimal hyperplasia and MCP-1 expression might be attributed to the antioxidant capacity of magnolol instead of lowering serum cholesterol. Magnolol may offer some protection against postangioplasty restenosis.