Hinokitiol, a natural tropolone derivative, offers neuroprotection from thromboembolic stroke in vivo

Thanasekaran Jayakumar, Wen Hsien Hsu, Ting Lin Yen, Jun Yun Luo, Yu Cheng Kuo, Tsorng Harn Fong, Joen Rong Sheu

Research output: Contribution to journalArticle

23 Citations (Scopus)

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)-1, inducible nitric oxide synthase (iNOS), tumor necrosis factor (TNF)-, 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-1, iNOS expression) and apoptosis (i.e., TNF-, 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.

Original languageEnglish
Article number840487
JournalEvidence-based Complementary and Alternative Medicine
Volume2013
DOIs
Publication statusPublished - 2013

Fingerprint

Tropolone
Stroke
Middle Cerebral Artery Infarction
Brain Ischemia
Hypoxia-Inducible Factor 1
Nitric Oxide Synthase Type II
Caspase 3
Tumor Necrosis Factor-alpha
Neuroprotection
beta-thujaplicin
Neuroprotective Agents
Ointments
Anti-Infective Agents
Reperfusion Injury
Cosmetics
Hair
Neoplasms
Tooth
Cell Proliferation
Apoptosis

ASJC Scopus subject areas

  • Complementary and alternative medicine

Cite this

Hinokitiol, a natural tropolone derivative, offers neuroprotection from thromboembolic stroke in vivo. / Jayakumar, Thanasekaran; Hsu, Wen Hsien; Yen, Ting Lin; Luo, Jun Yun; Kuo, Yu Cheng; Fong, Tsorng Harn; Sheu, Joen Rong.

In: Evidence-based Complementary and Alternative Medicine, Vol. 2013, 840487, 2013.

Research output: Contribution to journalArticle

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