Icariin intervenes in cardiac inflammaging through upregulation of SIRT6 enzyme activity and inhibition of the NF-kappa B pathway.

Yang Chen,Jianhua Huang,Tao Sun,Ding Yuan,Hong Fang,Waijiao Cai,Bill Kalionis,Junzhen Wu,Changcheng Zhang,Shijin Xia

doi:10.1155/2015/895976

Abstract

The 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-κB 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-κB (p65) protein expression in animal tissues and cell models. ICA upregulated the expression of SIRT6 and had an inhibitory effect on NF-κB inflammatory signaling pathways as shown by decreasing mRNA levels of the NF-κB downstream target genes TNF-α, ICAM-1, IL-2, and IL-6. Those 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-κB (a regulator of inflammation).

Highlights

Icariin is an important, active component in Herba Epimedii
The results suggest that SIRT6 protein expression in aged mice hearts was decreased when compared with young mice
We showed that treatment of young aortic Endothelial Cells (ECs) with the proinflammatory cytokine TNF-α resulted in increased levels of inflammatory cytokines that are downstream targets of NF-κB (TNF-α, ICAM-1, IL-2, and IL-6), with TNF-α mRNA levels showing the greatest increase (Figure 6(b))

Summary

Introduction

This well-known Chinese herbal medicine has proven efficacy 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]. Previous studies found that TFE prolongs the lifespan and has strong effects in 2BS cells [3], C. elegans [4], and Drosophila [5]. Icariin represents an important active component in TFE and exhibits similar life prolonging effects of TFE in C. elegans [8] and mice. ICA fulfills these requirements as an aging intervention drug and has been studied extensively over many years

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Discussion

Conclusion