RETRACTED ARTICLE: Attenuation of aortic injury by ursolic acid through RAGE-Nox-NFκB pathway in streptozocin-induced diabetic rats
Authors: Yaqin Zhang
Jing Ling
Min Xiang
Jianmei Wang
Xiaoyue Xu
Journal: Archives of pharmacal research (2012)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: Vascular complications; Diabetes mellitus; RAGE; NADPH oxidase; NF-κB
Affiliations: Biotechnology Center, Suzhou Health College, China.

Abstract:  Vascular complications are the leading causes of morbidity and mortality in diabetes mellitus (DM). The RAGE (receptor for advanced glycation end products)-NADPH oxidase-NF-κB signal transduction pathway plays an important role in the development of oxidative stress-related vascular complications in DM. Ursolic acid (UA), a pentacyclic triterpenoid derived from plants, has been reported to have multiple pharmacological effects, including a potent antioxidant activity. This study aimed to investigate both the effect of UA on aortic injury in streptozotocin (STZ)-induced diabetic rats and the drug's mechanism of action. STZ-induced diabetic animals were randomized in one of the following 4 groups: no treatment (diabetic model group), aminoguanidine (AG, 100 mg/kg), high-dose UA (50 mg/kg), and low-dose UA (25 mg/kg). A non-diabetic control group was followed concurrently. After 8 weeks, the diabetic model rats exhibited: severe aortic arch injury, histologically elevated serum glucose, fructosamine, and glycosylated hemoglobin; and accumulation of advanced glycation end products (AGEs) in the arota. In addition, the levels of RAGE protein, transcription factor NF-κB p65, and the p22phox subunit of NADPH oxidase were increased, as were the serum levels of malondialdehyde and tumor necrosis factor-alpha (TNF-α; p &lt; 0.01 vs control), suggesting that the mechanisms of oxidative stress contributed to vascular injury in the diabetic model group. In contrast, rats treated with UA (50 mg/kg) had a markedly less vascular injury and significantly improved biochemical parameters. Oxidative balance was also normalized in the UA-treated rats, and a marked reduction in the levels of RAGE and p22phox paralleled the reduced activation of NF-κB p65 and TNF-α (p &lt; 0.01 and p &lt; 0.05, respectively, vs diabetic model). These findings suggest that UA may suppress oxidative stress, thus blunting activation of the RAGE-NADPH oxidase-NF-κB signal transduction pathway, to ameliorate vascular injury in the STZ-induced DM rats. 

Retracted: Yes

PubPeer comments:
 2020retraction. https: link.springer.com article 10.1007 s12272-020-01262-x Retraction to: Archives of Pharmacal Research (2012) 35:877u2013886 https: doi.org 10.1007 s12272-012-0513-0 The authors have retracted this article (Xiang et al. 2012) because Fig. 4A and Fig. 4B are same as the left-hand panel and the middle panel respectively in Fig. 1 in an article published in Chinese by another author group (Wang et al. 2009). In addition, Associate Professor Xiaoning Li did not give permission to be acknowledged for pathology work. All authors agree with this retraction. References Wang J, Xiang M, Ling J, Xue X (2009) Effects of ursolic acid on the expression of nuclear factor-k B in the aorta of diabetic rat. Pharmacol Clin Chin Mater Med 25(1):11u201314 ,