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Baicalein attenuates intimal hyperplasia after rat carotid balloon injury through arresting cell-cycle progression and inhibiting ERK, Akt, and NF-κB activity in vascular smooth-muscle cells

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Abstract

Baicalein (5,6,7-trioxyflavone-7-O-beta-D-glucuronide) derived from the Chinese herb Scutellaria baicalensis is well known as a lipoxygenase inhibitor. We investigated baicalein-mediated inhibitory effects on vascular smooth-muscle cell (VSMC) proliferation and intimal hyperplasia by balloon angioplasty in the rat. In vascular injury studies, baicalein significantly suppressed intimal hyperplasia by balloon angioplasty. Baicalein significantly inhibited cell proliferation via a lipoxygenase-independent pathway using [3H]thymidine incorporation, 3-(4,5-dimethylthiazol-2-yl)2,5-diphenyltetrazolium bromide (MTT), and flow cytometry assays. At the concentrations used, no cytotoxic effect on cell culture was found. Baicalein blocks cell-cycle progression in S/G2/M phase, consistent with the cell-cycle effects, baicalein significant inhibited cyclin D1, p42/44 mitogen-activated protein kinase (MAPK), and Akt phosphorylation without change in the other cell-cycle regulatory proteins. Furthermore, baicalein attenuated serum-induced deoxyribonucleic acid (DNA) binding activity of nuclear factor kappa B (NF-κB). These results show that baicalein blocks cell proliferation via blocking cell-cycle progression and proliferating events, including p42/44 MAPK and Akt activations as well as NF-κB activation. It also inhibits intimal hyperplasia after balloon vascular injury in the rat, indicating the therapeutic potential for treating restenosis after arterial injury.

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Acknowledgments

This work was supported by research grants of the National Science Council of the Republic of China (NSC-96–2628-B002–109-MY3 and NSC96–2321-B-002–031-MY2).

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Authors and Affiliations

  1. Pharmacological Institute, College of Medicine, National Taiwan University, No. 1, Jen-Ai Road, Sect. 1, Taipei, Taiwan

    Chieh-Yu Peng, Shiow-Lin Pan, Ying-Wen Huang, Ya-Ling Chang & Che-Ming Teng

  2. School of Pharmacy, College of Medicine, National Taiwan University, No. 1, Jen-Ai Road, Sect. 1, Taipei, Taiwan

    Jih-Hwa Guh

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  1. Chieh-Yu Peng
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  2. Shiow-Lin Pan
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Correspondence to Shiow-Lin Pan or Che-Ming Teng.

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C.-Y. Peng and Y.-W. Huang contributed equally to this work.

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Peng, CY., Pan, SL., Huang, YW. et al. Baicalein attenuates intimal hyperplasia after rat carotid balloon injury through arresting cell-cycle progression and inhibiting ERK, Akt, and NF-κB activity in vascular smooth-muscle cells. Naunyn-Schmied Arch Pharmacol 378, 579–588 (2008). https://doi.org/10.1007/s00210-008-0328-1

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