Research Article Icariin Intervenes in Cardiac Inflammaging through Upregulation of SIRT6 Enzyme Activity and Inhibition of the NF-Kappa B Pathway Yang Chen, 1 Tao Sun, 2 Junzhen Wu, 2 Bill Kalionis, 3 Changcheng Zhang, 4 Ding Yuan, 4 Jianhua Huang, 5 Waijiao Cai, 5 Hong Fang, 6 and Shijin Xia 2 1 Center of Disease Prevention and Treatment, Shanghai Guanghua Hospital of Integrative Traditional Chinese and Western Medicine, Shanghai 200052, China 2 Department of Geriatrics, Shanghai Institute of Geriatrics, Huadong Hospital, Fudan University, Shanghai 200040, China 3 Department of Perinatal Medicine, Pregnancy Research Centre and University of Melbourne Department of Obstetrics and Gynaecology, Royal Women’s Hospital, Parkville, VIC 3052, Australia 4 Medical College, China ree Gorges University, Yichang 443002, China 5 Key Laboratory of Cellular and Molecular Biology, Huashan Hospital, Fudan University, Shanghai 200040, China 6 Department of Diseases Prevention and Healthcare, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China Correspondence should be addressed to Shijin Xia; xiashijinhd@163.com Received 19 June 2014; Revised 23 July 2014; Accepted 7 August 2014 Academic Editor: Javier Gonz´ alez-Gallego Copyright © 2015 Yang Chen et al. is 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. e aim of the study was to investigate the effect of icariin (ICA) on cardiac aging through its effects on the SIRT6 enzyme and on the NF-B pathway. Investigating the effect of ICA on the enzymatic activity of histone deacetylase SIRT6 revealed a concentration of 10 −8 mol/L ICA had a maximum activating effect on histone deacetylase SIRT6 enzymatic activity. Western analysis showed that ICA upregulated SIRT6 protein expression and downregulated NF-B (p65) protein expression in animal tissues and cell models. ICA upregulated the expression of SIRT6 and had an inhibitory effect on NF-B inflammatory signaling pathways as shown by decreasing mRNA levels of the NF-B downstream target genes TNF-, ICAM-1, IL-2, and IL-6. ose effects were mediated directly or indirectly by SIRT6. We provided evidence that inflammaging may involve a novel link between the effects of ICA on SIRT6 (a regulator of aging) and NF-B (a regulator of inflammation). 1. Introduction Icariin is an important, active component in Herba Epimedii. is well-known Chinese herbal medicine has proven effi- cacy in treating cardiovascular diseases and osteoporosis and in improving sexual and neurological function and is widely used to treat particular age-related diseases in oriental countries [1, 2]. Total flavone of Epimedium (TFE) is generally considered to be the active compound found in Herba Epimedii. Previous studies found that TFE prolongs the lifespan and has strong effects in 2BS cells [3], C. elegans [4], and Drosophila [5]. In addition, urine and plasma metabonomic studies showed TFE treatment altered age- related changes in aging rats to levels consistent with younger rats [6, 7]. Icariin represents an important active component in TFE and exhibits similar life prolonging effects of TFE in C. elegans [8] and mice. A significant feature of the natural aging process is that body function decline is chronic and progressive; therefore the desired intervention drug must have a therapeutic effect as well as being safe, have nontoxic side effects, and be suitable for long-term use. ICA fulfills these requirements as an aging intervention drug and has been studied extensively over many years. Worldwide, research on delaying aging has a major focus on the silent information regulation protease family of Sirtuins [9]. Sirtuins belong to the Sir2 family of NAD(+)- dependent deacetylases and they regulate longevity in yeast, Hindawi Publishing Corporation BioMed Research International Volume 2015, Article ID 895976, 12 pages http://dx.doi.org/10.1155/2015/895976