Magnolol induces apoptosis in vascular smooth muscle.
Magnolol, an active component extracted from Magnolia officinalis, has various pharmacological effects, including potent antioxidant activity. In the present study, we investigated the effect of magnolol on apoptosis in rat vascular smooth muscle cells (VSMCs), using terminal-deoxynucleotidyl-transferase-mediated deoxyuridine triphosphate nick end labelling (TUNEL) and flow cytometric analysis. Magnolol (5-20 micro M) concentration-dependently induced significant VSMC apoptosis, this effect being blocked by the caspase inhibitor benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone (z-VAD-fmk, 50 micro M). To study the molecular mechanism, the mitochondrial death pathway was examined. Magnolol increased caspase-3 and caspase-9 activities significantly and reduced the mitochondrial potential (Deltapsi(m)). The levels of B-cell leukaemia/lymphoma-2 (Bcl-2), but not those of Bcl-2-associated X protein (Bax) or Bcl-x(L), were down-regulated concentration dependently by magnolol. In an animal model, balloon angioplasty-induced neointima formation was inhibited significantly by magnolol and Bcl-2 protein levels were reduced. Taken together, these results show that magnolol induces apoptosis in VSMCs via the mitochondrial death pathway. This effect is mediated through down-regulation of Bcl-2 protein levels, both in vivo and in vitro. Magnolol thus shows potential as a novel therapeutic agent for the treatment of atherosclerosis and re-stenosis.
Chen
Jiun-Han
JH
National Defence Medical Centre, 114, Taipei, Taiwan.
Wu
Chin-Chen
CC
Hsiao
George
G
Yen
Mao-Hsiung
MH
D000800:Angioplasty, Balloon; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001713:Biphenyl Compounds / Q000494:pharmacology*; D002340:Carotid Artery Diseases / Q000209:etiology / Q000473:pathology; D053148:Caspase 3; D053453:Caspase 9; D020169:Caspases / Q000096:biosynthesis; D002478:Cells, Cultured; D003251:Constriction, Pathologic; D015536:Down-Regulation; D004789:Enzyme Activation; D017705:Lignans; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D008931:Mitochondria, Muscle / Q000187:drug effects / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects*; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein
D000975:Antioxidants; C494828:Bax protein, rat; C494813:Bcl2l1 protein, rat; D001713:Biphenyl Compounds; D017705:Lignans; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein; C005498:magnolol; C505410:Casp3 protein, rat; C506435:Casp9 protein, rat; D053148:Caspase 3; D053453:Caspase 9; D020169:Caspases