Picrorhiza scrophulariiflora improves accelerated atherosclerosis through inhibition of redox-sensitive inflammation Zhi Jian Guo, Fan Fan Hou ⁎ , Shang Xi Liu, Jian Wei Tian, Wei Ru Zhang, Di Xie, Zhan Mei Zhou, Zhi Qiang Liu, Xun Zhang Division of Nephrology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, PR China Received 31 August 2008; received in revised form 29 October 2008; accepted 13 December 2008 Available online 29 January 2009 Abstract Background: Accumulation of advanced glycation end products (AGEs) or advanced oxidation protein products (AOPPs) has been identified as a risk factor for accelerated atherosclerosis seen in diabetes and chronic kidney disease. However, little is known about the intervention for atherogenesis associated with these oxidized proteins. The rhizome of Picrorhiza scrophulariiflora (PS) has long been used to treat inflammatory diseases as a traditional medication. The study was performed to test the hypothesis that ethanol extraction of PS (EPS) may improve AGEs- or AOPPs-induced accelerated atherosclerosis in vivo. Methods and results: Hypercholesterolemic or normal rabbits were randomly assigned to 8 groups treated with intravenous injection of AGEs- or AOPPs-modified rabbit serum albumin (AGEs-RSA or AOPPs-RSA), unmodified RSA or vehicle in the presence or absence of EPS (10 mg/kg/2 days) gavage for 10 weeks. Compared with hypercholesterolemic rabbits without EPS treatment, EPS administration significantly decreased the aortic plaque volume and oxidized low density lipoprotein (Ox-LDL) deposition in hypercholesterolemic animals. This was accompanied by significant histological improvement including decrease of intimal and smooth muscle cell proliferation and macrophage influx in affected areas. EPS administration almost completely abolished the accelerated atherosclerosis induced by chronic treatment of AGEs- or AOPPs-RSA in both hypercholesterolemic and normal rabbits. EPS administration significantly restored the AGEs- or AOPPs-induced redox imbalance and inflammation, evidenced by decrease of plasma Ox-LDL, thiobarbituric acid reactive substances and TNF-α, and increase of glutathione peroxidase activity. Conclusion: These data suggested that EPS may improve atherosclerosis, particularly that induced by AGEs or AOPPs, through inhibition of redox-sensitive inflammation. © 2008 Elsevier Ireland Ltd. All rights reserved. Keywords: Picrorhiza scrophulariiflora; Advanced glycation end products; Advanced oxidation protein products; Accelerated atherosclerosis 1. Introduction The high prevalence of atherosclerosis has been amply documented in patients with diabetes and chronic kidney disease (CKD) [1,2]. Although the underlying mechanism of the accelerated atherosclerosis remains to be elucidated, many risk factors associated with diabetic pathophysiology and/or renal dysfunction have been verified, including hyperlipidemia, endothelial dysfunction, homocystinemia, microinflammation and oxidative stress [3,4]. Diabetes and chronic renal insufficiency are associated with increased modification of proteins. A typical represen- tation is the formation of advanced glycation end products (AGEs), the products of nonenzymatic glycation/oxidation of proteins, and accumulation of advanced oxidation protein products (AOPPs), a family of oxidized protein compounds [5–7]. Both AGEs and AOPPs promote atherosclerosis in hyperlipidemic, diabetic or the remnant kidney models, probably through triggering inflammation and oxidative International Journal of Cardiology 136 (2009) 315 – 324 www.elsevier.com/locate/ijcard ⁎ Corresponding author. Division of Nephrology, Nanfang Hospital, Southern Medical University, 1838 North Guangzhou Avenue, Guangzhou, 510515, P. R. China. Tel.: +86 20 61641591; fax: +86 20 87281713. E-mail address: ffhou@public.guangzhou.gd.cn (F.F. Hou). 0167-5273/$ - see front matter © 2008 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.ijcard.2008.12.102