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Evidence-Based Complementary and Alternative Medicine
Volume 2013, Article ID 840487, 8 pages
http://dx.doi.org/10.1155/2013/840487
Research Article

Hinokitiol, a Natural Tropolone Derivative, Offers Neuroprotection from Thromboembolic Stroke In Vivo

1Department of Pharmacology, Graduate Institute of Medical Sciences, Taipei Medical University, 250 Wu-Hsing Street, Taipei 110, Taiwan
2Department of Surgery, Wan-Fang Hospital, Taipei Medical University, 111 Hsing-Long Road, Taipei 110, Taiwan
3Department of Anatomy, College of Medicine, Taipei Medical University, Taipei 110, Taiwan

Received 17 July 2013; Accepted 9 September 2013

Academic Editor: Mao-Hsiung Yen

Copyright © 2013 Thanasekaran Jayakumar et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Hinokitiol (β-thujaplicin), a tropolone-related compound found in the heartwood cupressaceous plants, is widely used in hair tonics, tooth pastes, cosmetics, and food as an antimicrobial agent. Increasing evidence has confirmed that hinokitiol exhibits anticancer activity in a variety of cancers through inhibition of cell proliferation. In the present study, we have investigated the neuroprotective effect and mechanisms of hinokitiol in rats against middle cerebral artery occlusion (MCAO)-induced thromboembolic stroke. Treatment with hinokitiol (0.2 and 0.5 mg/kg; intraperitoneally) 30 min before MCAO dose dependently attenuated cerebral ischemia and improved neurobehavioral deficits in cerebral ischemic rats. Intraperitoneal administration of hinokitiol significantly reduced infarct size compared to that in control rats. MCAO-induced focal cerebral ischemia was associated with increased expressions of hypoxia-inducible factor (HIF)-1α, inducible nitric oxide synthase (iNOS), tumor necrosis factor (TNF)-α, and active caspase-3 in ischemic regions. However, these expressions were obviously inhibited by hinokitiol (0.2 and 0.5 mg/kg) treatment. This study demonstrates for the first time that in addition to being originally considered as an agent against microbes and variety of cancers, hinokitiol possesses potent neuroprotective activity. This activity is mediated, at least in part, by inhibition of inflammatory responses (i.e., HIF-1α, iNOS expression) and apoptosis (i.e., TNF-α, active caspase-3), resulting in a reduction of infarct volume and improvement in neurobehavior in rats with cerebral ischemia. Therefore, the therapeutic potential of hinokitiol may lead to novel role for treatment or prevention of ischemia/reperfusion injury-related disorders.