title: Elucidating the inhibitory mechanisms of magnolol on rat smooth muscle cell proliferation.
abstract: The pathological mechanism of percutaneous transluminal coronary angioplasty-induced restenosis has been attributed to outgrowth of vascular smooth muscle cells. Pretreatment with antioxidants has been shown to reduce restenosis. Magnolol, an active compound of Magnolia officinalis, has exhibited approximately 1,000 times more potent antioxidant effects than alpha-tocopherol. In this study, we demonstrate, using cytometric analysis, an approximate 61% reduction of smooth muscle cells progressing to the S-phase by 0.05 mg/ml of magnolol. A BrdU incorporation assay also showed a significant reduction (73%) of DNA synthesis using 0.05 mg/ml of magnolol. The protein level of the proliferating cell nuclear antigen was suppressed by approximately 48% using 0.05 mg/ml of magnolol. This was in agreement with the promoter activity of nuclear factor-kappa B, which was also attenuated by 0.05 mg/ml of magnolol. Since receptor interacting protein and caspase-3 protein expression levels were both increased by magnolol in a dose-dependent manner, the apoptotic pathway may mediate the inhibition of cell growth. Our finding that malondialdehyde formation was significantly inhibited by 0.05 mg/ml of magnolol further supported the antioxidant effect of magnolol. These studies suggest that magnolol might be a potential pharmacological reagent in preventing balloon injury-induced restenosis.
authors.affiliation: Department of Pharmacology, School of Medicine, China Medical University, Taiwan. chhswu@mail.cmu.edu.tw
authors.forename: Chieh-Hsi
authors.initials: CH
authors.lastname: Wu
authors.forename: Chih-Wen
authors.initials: CW
authors.lastname: Chen
authors.forename: Ho-Chih
authors.initials: HC
authors.lastname: Chen
authors.forename: Weng-Cheng
authors.initials: WC
authors.lastname: Chang
authors.forename: Min-Ji
authors.initials: MJ
authors.lastname: Shu
authors.forename: Jui-Sung
authors.initials: JS
authors.lastname: Hung
mesh_terms: D015906:Angioplasty, Balloon, Coronary; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001713:Biphenyl Compounds / Q000494:pharmacology*; D015153:Blotting, Western; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D023903:Coronary Restenosis / Q000517:prevention & control; D004247:DNA / Q000096:biosynthesis / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D017705:Lignans / Q000494:pharmacology*; D008315:Malondialdehyde / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000166:cytology* / Q000187:drug effects; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D011401:Promoter Regions, Genetic; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D051381:Rats; D047988:Tumor Necrosis Factor Receptor-Associated Peptides and Proteins / Q000378:metabolism
chemical_list: D000975:Antioxidants; D001713:Biphenyl Compounds; D017705:Lignans; D016328:NF-kappa B; D018809:Proliferating Cell Nuclear Antigen; D047988:Tumor Necrosis Factor Receptor-Associated Peptides and Proteins; C005498:magnolol; D008315:Malondialdehyde; D004247:DNA; D017346:Protein Serine-Threonine Kinases; C505410:Casp3 protein, rat; D053148:Caspase 3; D020169:Caspases