Cinnamaldehyde Prevents Endothelial Dysfunction Induced by High Glucose by Activating Nrf2

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1 315 Accepted: Wang et al.: March Cinnamaldehyde 11, 2015 Prevents Endothelial Dysfunction /15/ $39.50/0 Under High Glucose Original Paper This is an Open Access article licensed under the terms of the Creative Commons Attribution- NonCommercial 3.0 Unported license (CC BY-NC) ( applicable to the online version of the article only. Distribution permitted for non-commercial purposes only. Cinnamaldehyde Prevents Endothelial Dysfunction Induced by High Glucose by Activating Nrf2 Fang Wang a Chunhua Pu a Peng Zhou a Peijian Wang a Dengpan Liang a Qiulin Wang a b Binghu Li c d a b Department of Integrated Traditional Chinese and Western Medicine, Chengdu Military General c Military Medical University, Chongqing, d Department of Cardiology, Nephrology and Endocrinology, Key Words Abstract Background/Aims: have a cardiovascular protective effect, but its role in endothelial dysfunction induced by high glucose is unknown. Methods: cultured in normal glucose(ng 5. or without CA (10 M). Results: these effects were reversed by Nrf2-siRNA in high glucose conditions. Conclusion: Our results indicated that CA protected endothelial dysfunction under high glucose conditions and this effect was mediated by Nrf2 activation and the up-regulation of downstream target proteins. CA administration may represent a promising intervention in diabetic patients who are at risk for vascular complications. F. Wang and C. Pu contribute equally to this work. Peijian Wang Copyright Chengdu, Sichuan (PR China); or Department of Integrated Traditional (PR China); wpjmed@aliyun.com or huyonghe@vip.126.com

2 316 Introduction Diabetes mellitus (DM) is a major and an increasing health problem worldwide. Its related vascular complications are the major cause of morbidity and mortality [1]. Studies endothelial dysfunction in diabetic patients without clinical signs of macrovascular disease, such as ischemic heart disease and stroke [2]. It is well documented that the major cause with the potential to ameliorate hyperglycemia-induced vascular lesions. However, the use of controversial [4, 5]. as a physiological regulator of ROS generation and may contribute to the prevention of defense against ROS produced under hyperglycemic conditions and thus protected pancreatic glucose are unknown. Materials and Methods Artery and endothelial cell culture 2. The cells

3 317 Cinnamaldehyde treatment RNA interference of Nrf2 Measurement of vascular activities Measurement of ROS production aortic sections were cut open, and the endothelium was inverted and placed between two coverslips for Evaluation of NO levels Western blotting analysis Statistical analysis E t-test. Two-sided P Results Cinnamaldehyde preserved in vitro endothelium-dependent relaxation of mice aortas under high glucose P >0.05

4 318 Fig. 1. in vitro mm, 24 h) impaired the endothelium-depen- in vitro dysfunction in mouse aortas under high-glucose conditions but not in normal-glucose conditions. **P<0.01 ## P<0.01 Fig. 2. namaldehyde inhibited ROS p r o d u c t i o n and preserved mice aortas treated with high glucose ex vivo. p r o d u c t i o n measured by in the en face endothelium of aortas from after treat- group) or on measured staining in the en face **P<0.01 ver- ## P<0.01

5 319 Fig. 3.- nucleus. **P<0.01 ## P<0.01 Cinnamaldehyde inhibited ROS production and prevented NO reduction in mouse aortas treated with high glucose in vitro en face endothelium of the aorta was higher in the HG than in the ROS production in the endothelium of the increased ROS levels in the en face endothelium of the aorta accompanied in the endothelium under high glucose decreased the ROS levels and increased P >0.05. Cinnamaldehyde acts as an Nrf2 activator in high glucose-treated ECs O 2 Cinnamaldehyde diminished ROS levels and preserved NO levels in ECs under high glucose conditions

6 320 Fig and levels of nitrotyrosine. - mm) and HG plus - **P<0.01 versus the normal ## P<0.01 versus - ting. **P<0.01 ## P<0.01 versus HG group. Data are the means ± Discussion

7 321 Fig. 5. high glucose-induced ROS production and pre- - - images and data from increased the levels of administration decrea- vels under high-glucose conditions. These effects were blocked by Representative images **P <0.01 versus ; ## P <0.01 versus P <0.01±

8 322 complications. The primary causative factor leading to the pathophysiologic alterations in the developments in anti-diabetic therapy, diabetic vascular complications continue to be seriously detrimental [17]. Therefore, it is critical to pursue novel strategies for preventing the vascular complications associated with diabetes. diabetic vascular complications, but its direct effect on endothelial dysfunction induced by high glucose was unknown. treatment for 24. Many cardiovascular diseases, including diabetic vascular complications, are associated in cardiovascular diseases such as atherosclerosis, hypertension, and heart failure due to. in vitro and in vivo endothelial cells with high glucose for 7 days decreased the HO-1 activity and cell viability.

9 323 be responsible for the decreased nitrotyrosine levels. for vascular complications. Acknowledgments Disclosure Statement this paper. References Herbal medicines and nutraceuticals for diabetic vascular complications: mechanisms of action and

10 activation enhances gut glucagon-like peptide-1 secretion and improves glucose homeostasis. Diabetes