Hindawi Publishing Corporation Evidence-Based Complementary and Alternative Medicine Volume 2012, Article ID 284963, 11 pages doi:10.1155/2012/284963 Research Article The Chinese Herbal Decoction Danggui Buxue Tang Inhibits Angiogenesis in a Rat Model of Liver Fibrosis Jing Lv, 1 Zhimin Zhao, 1 Yuan Chen, 1 Qinglan Wang, 1 Yanyan Tao, 1 Li Yang, 2 Tai-Ping Fan, 3 and Chenghai Liu 1, 4, 5 1 Institute of Liver Diseases, ShuGuang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China 2 The MOE Key Laboratory for Standardization of Chinese Medicines and the SATCM Key Laboratory for New Resources and Quality Evaluation of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai 201210, China 3 Angiogenesis & Chinese Medicine Laboratory, Department of Pharmacology, University of Cambridge, Cambridge CB2 1PD, UK 4 E-Institute of TCM Internal Medicine, Shanghai Municipal Education Commission, Shanghai 201203, China 5 Shanghai Key Laboratory of Traditional Chinese Clinical Medicine, Shanghai 201203, China Correspondence should be addressed to Tai-Ping Fan, tpf1000@cam.ac.uk and Chenghai Liu, chenghai liu@yahoo.com.cn Received 20 February 2012; Revised 13 May 2012; Accepted 14 May 2012 Academic Editor: Chang-Quan Ling Copyright © 2012 Jing Lv 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. In this study, we investigated the anti-angiogenic effect of the Chinese herbal decoction Danggui Buxue Tang (DBT; Radix Astragali and Radix Angelicae sinensis in 5 : 1 ratio) in a rat model of liver fibrosis, in order to elucidate its mechanisms of action against liver fibrosis. Liver fibrosis was induced with CCl 4 and high-fat food for 6 weeks, and the rats were treated with oral doses of DBT (6 g raw herbs/kg/d) and N-Acetyl-L-cysteine (NAC; 0.1 g/kg/d). The results showed that both DBT and NAC attenuated liver fibrosis and neo-angiogenesis. Furthermore, DBT and NAC improved SOD activity but decreased MDA content and 8-OH-dG in fibrotic livers, with DBT being more effective than NAC. DBT decreased the expression of VEGF, Ang1 and TGF-β1 and their signaling mediators, whereas NAC had no effect on VEGF and VEGFR2 expression. Both DBT and NAC reduced HIF-1α gene and protein expression in fibrotic livers, with DBT being more effective. These data clearly demonstrate that the anti-fibrotic properties of DBT are related to its ability to inhibit angiogenesis and its anti-angiogenic mechanisms are associated with improving oxidative stress, regulating the expression and signaling of angiogenic factors, and especially modulating HIF-1α in fibrotic livers. 1. Introduction Angiogenesis is a hypoxia-driven and growth factor-de- pendent process that leads to the formation of neovas- culature from preexisting blood vessels. Experimental and clinical studies have unequivocally shown that pathological angiogenesis, irrespective of etiology, plays a key role in the fibrogenic progression of chronic liver diseases [1–3], and the inhibition of pathological angiogenesis in liver not only can stop liver cancer development, but also regress or reverse liver fibrosis [4, 5]. Danggui Buxue Tang (DBT), an ancient traditional Chi- nese herbal formula composed of Huangqi (Radix Astragali) and Danggui (Radix Angelica sinensis) with a weight ratio of 5 : 1, has wide pharmacological actions, including regulation of immune functions and protection against liver injuries [6]. Although there are no reports concerning the effect of DBT on liver cirrhosis, several studies have reported antifibrotic effects for its components. For example, the combination of Astragali and Angelicae sinensis significantly inhibited the progression of renal fibrosis. This treatment led to a decrease in histologic damage, type III and IV collagen expression, fibronectin, and laminin in a rat model of chronic puromycin-induced nephrosis [7]. Astragali sig- nificantly attenuated liver tissue collagen and hydroxyproline (Hyp) content in a rat model of liver fibrosis induced by albumin immune complex [8]. In a rat model of pulmonary fibrosis induced by intratracheal instillation of bleomycin,