Journal of Ethnopharmacology 113 (2007) 292–299 Buyang Huanwu Decoction can improve recovery of neurological function, reduce infarction volume, stimulate neural proliferation and modulate VEGF and Flk1 expressions in transient focal cerebral ischaemic rat brains Guangxian Cai a,∗ , Baiyan Liu b , Wei Liu a , Xianhui Tan c , Jianhui Rong d , Xuemei Chen a , Li Tong e , Jiangang Shen c,∗∗ a Hunan Traditional Chinese Medicine University, Changsha 410007, China b School of Chinese Medicine, Chinese University of Hong Kong, Shatin, N.T., Hong Kong, China c School of Chinese Medicine, University of Hong Kong, 21 Sassoon Road, Hong Kong, China d Molecular Chinese Medicine Laboratory, University of Hong Kong, 21 Sassoon Road, Hong Kong, China e School of Chinese Medicine, Southern Medical University, Guangzhou 515015, China Received 8 November 2006; received in revised form 7 June 2007; accepted 20 June 2007 Available online 27 June 2007 Abstract Buyang Huanwu Decoction is a classic formula for treating stroke-induced disability in traditional Chinese medicine (TCM). To explore its pharmacological basis, we investigated the effects of the whole formula and its herbal components on the neurological behavior performance and infarction volume in focal cerebral ischaemia rats. The neurological deficit scores and infarction volume were measured at days 3, 7 and 14 after 30 min of occlusion of middle cerebral artery. The results showed that Buyang Huanwu Decoction and its herbal components significantly improved the neurological behavior performances and reduced the infarction volume in the ischaemic brains. To elucidate the potential therapeutic mechanisms, we investigated the proliferation of progenitors by detecting the immunohistochemical staining of thymidine analog 5-bromo-2 ′ - deoxyuridine (BrdU) and found that the formula stimulated the proliferation of the progenitors at hippocampus and subventricular zone (SVZ) in the ischaemic brains. As vascular endothelial growth factor (VEGF) and its receptor fetal liver kinase (Flk1) are important neurotrophic, neuroprotective and neuroproliferative factors, we studied the expressions of VEGF and Flk1 in the hippocampus, SVZ and cortex in the ischaemic brains and found that the formula led to increase the numbers of VEGF-positive and Flk1-positive cells in the SVZ and cortex in the ischaemic brains. The results indicate that the therapeutic effects of Buyang Huanwu Decoction for recovery of neurological deficits are associated with the stimulation of the proliferation of progenitors and the enhancement of the expressions of VEGF and Flk in ischaemic brains. © 2007 Elsevier Ireland Ltd. All rights reserved. Keywords: Buyang Huanwu Decoction; Focal cerebral ischaemia; Proliferation; VEGF; Flk1 Abbreviations: VEGF, vascular endothelial growth factor; Flk, fetal liver kinase; Flt, fams-like tyrosine; MCAO, middle cerebral artery occlusion; BHD- 01, whole formula of Buyang Huanwu Decoction; BHD-02, herbal components of Buyang Huanwu Decoction; RAM, Radix Astragali membranaceus; BrdU, 5- bromo-2 ′ -deoxyuridine; PBS, phosphate buffered saline; GAP, good agricultural practice; SVZ, subventricular zone; TTC, 2,3,5-triphenyltetrazolium chloride; TCM, traditional Chinese medicine; min, minutes; h, hours; BBB, blood brain barrier ∗ Corresponding author. Tel.: +86 731 5381456; fax: +86 731 5504879. ∗∗ Corresponding author. Tel.: +852 2589 0429; fax: +852 2872 5476. E-mail addresses: lby1203@sina.com (G. Cai), shenjg@hkucc.hku.hk (J. Shen). 1. Introduction Adult mammalian central nervous system (CNS) has long been believed to be incapable of self-repair or regeneration (Bjorklund and Lindvall, 2000). Recent evidence has revealed that progenitors in adult CNS can potentially generate new func- tional neurons and repair the damaged CNS (Dirnagl et al., 1999). Adult CNS contains a range of progenitors with lim- ited capacities of growth and differentiation. Progenitor cells in subventricular zone (SVZ) of lateral ventricle, dentate gyrus of hippocampus and cortex exhibit distinct profiles of cellular proliferation and differentiation in response to ischaemic brain 0378-8741/$ – see front matter © 2007 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.jep.2007.06.007