Neuroscience Letters 417 (2007) 261–265 Tanshinone IIB, a primary active constituent from Salvia miltiorrhza, exhibits neuro-protective activity in experimentally stroked rats Xi-Yong Yu a , Shu-Guang Lin b,∗∗ , Zhi-Wei Zhou c , Xiao Chen d , Jun Liang e , Wei Duan f , Xue-Qing Yu g , Jing-Yuan Wen h , Balram Chowbay i , Chun-Guang Li j , Fwu-Shan Sheu k , Eli Chan l , Shu-Feng Zhou m,∗ a Research Center of Medical Sciences, Guangdong Provincial People’s Hospital, Guangdong Provincial Cardiovascular Institute, Guangzhou 510080, China b Department of Cardiology, Guangdong Provincial People’s Hospital, Guangdong Provincial Cardiovascular Institute, 96 Dongchuan Road, Guangzhou 510080, China c Department of Biological Science and Biotechnology, College of Bioengineering, Nanchang University, Nanchang, China d Department of Pharmacy, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China e Department of Pharmacology and Toxicology, Australian Institute of Chinese Medicine, Sydney, New South Wales 2118, Australia f School of Medicine, Deakin University, Waurn Ponds, Victoria 3217, Australia g Department of Nephrology, the First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China h School of Pharmacy, Faculty of Medical and Health Sciences, the University of Auckland, Auckland, New Zealand i Clinical Pharmacology Lab, Division of Medical Sciences, National Cancer Centre, Singapore 169610 j The Chinese Medicine Research Group, Division of Chinese Medicine, RMIT University, Australia k Department of Biological Sciences, National University of Singapore, 14 Science Drive 4, Singapore 117543 l Department of Pharmacy, National University of Singapore, Singapore m Division of Pharmacy, School of Life Sciences, Faculty of Sciences, Queensland University of Technology, 2 George Street, GPO Box 2434, Brisbane, Queensland 4001, Australia Received 29 December 2006; received in revised form 23 February 2007; accepted 23 February 2007 Abstract Tanshinone IIB (TSB) is a major active constituent of the root of Salvia miltiorrhiza (Danshen) used in the treatment of acute stroke. Danshen extracts and TSB have shown marked neuron-protective effects in mouse studies but there is a lack of clinical evidence for the neuron-protective effects of Danshen and its active ingredients. This study investigated the neuron-protective effects of TSB in experimentally stroked rats. TSB at 5 and 25 mg/kg by intraperitoneal injection significantly reduced the focal infarct volume, cerebral histological damage and apoptosis in rats subjected to middle cerebral artery occlusion (MCAO) compared to MCAO rats receiving vehicle. This study demonstrated that TSB was effective in reducing stroke-induced brain damage and may represent a novel drug candidate for further development. Further mechanistic studies are needed for the neuron-protective activity of TSB. © 2007 Elsevier Ireland Ltd. All rights reserved. Keywords: Stroke; Tanshinone IIB; Focal infarct; Middle cerebral artery occlusion; Rat Stroke is a life-threatening disease characterized by rapidly developing clinical signs of focal or global disturbance of cere- bral function, with symptoms lasting 24 h or up to weeks, or leading to death with no apparent cause other than of vas- cular origin [5]. Recently, intense interest has focused on the ∗ Corresponding author. Tel.: +61 7 31381340; fax: +61 7 31381534. ∗∗ Corresponding author. Tel.: +86 20 83827812x21180; fax: 86 20 83827712. E-mail addresses: yuxycn@hotmail.com (S.-G. Lin), s4.zhou@qut.edu.au (S.-F. Zhou). antioxidant properties of natural products due to their purported neuro-protective effects in patients [17]. Among these natural products, the dried root of S. miltiorrhiza (Danshen) is widely used in the treatment of stroke [16,12]. It is estimated that there are approximately 5 million patients with stroke use Danshen and the global market value is about 2 billion of US dol- lars in 2005 [16]. Danshen extracts mainly contain diterpene quinine analogs, including tanshinone I, dihydrotanshinone, tanshinone IIA, tanshinone IIB (TSB, (Fig. 1), and cryptotan- shinone (CTS) [6]. Danshen extracts and TSB have shown 0304-3940/$ – see front matter © 2007 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.neulet.2007.02.079