Abstract
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 µM) concentration-dependently induced significant VSMC apoptosis, this effect being blocked by the caspase inhibitor benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone (z-VAD-fmk, 50 µM). 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 (Δψm). The levels of B-cell leukaemia/lymphoma-2 (Bcl-2), but not those of Bcl-2-associated X protein (Bax) or Bcl-xL, 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.
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Acknowledgements
We are grateful to Professor A-R Lee (Department of Pharmacy, National Defence Medical Centre, Taiwan) for providing synthetic magnolol. This study was supported by a grant from the Foundation of Biomedical Sciences and grant NSC90-2315-B-016-002 (to M-H. Y.) from the National Science council, Taipei, Taiwan, ROC.
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Chen, JH., Wu, CC., Hsiao, G. et al. Magnolol induces apoptosis in vascular smooth muscle. Naunyn-Schmiedeberg's Arch Pharmacol 368, 127–133 (2003). https://doi.org/10.1007/s00210-003-0779-3
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DOI: https://doi.org/10.1007/s00210-003-0779-3