Bisdemethoxycurcumin Increases Sirt1 to Antagonizet-BHP-Induced Premature Senescence in WI38 Fibroblast Cells

Ying-Bo Li,Qing-Wen Zhang,Pui-Man Hoi,Zhang-Feng Zhong,Guo-Sheng Wu,Jiao-Lin Bao,Mei-Wan Chen,Simon Ming-Yuen Lee,Yi-Tao Wang

doi:10.1155/2013/851714

Ying-Bo Li, Qing-Wen Zhang + Show 7 more

Open Access

https://doi.org/10.1155/2013/851714

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Abstract

Curcuminoids are well known for their capabilities to combat risk factors that are associated with ageing and cellular senescence. Recent reports have demonstrated that curcuminoids can extend the lifespan of model organisms. However, the underlying mechanisms by which these polyphenic compounds exert these beneficial effects remain unknown. In this study, t-BHP-induced premature senescence model in human fibroblasts was chosen to explore the protective effects of a curcuminoid, bisdemethoxycurcumin (BDMC), on cellular senescence. The results demonstrated that BDMC attenuated oxidative stress-induced senescence-like features which include the induction of an enlarged cellular appearance, higher frequency of senescence-associated β-galactosidase staining activity, appearance of senescence-associated heterochromatic foci in nuclei, decrease in proliferation capability, and alteration in related molecules such as p16 and retinoblastoma protein. Notably, we found that BDMC treatment activated Sirt1/AMPK signaling pathway. Moreover, downregulating Sirt1 by the pharmacological inhibitor nicotianamine or small interfering RNA blocked BDMC-mediated protection against t-BHP-mediated decrease in proliferation. These results suggested that BDMC prevented t-BHP-induced cellular senescence, and BDMC-induced Sirt1 may be a mechanism mediating its beneficial effects.

Highlights

Curcuminoids, including curcumin, demethoxycurcumin, and bisdemethoxycurcumin (BDMC), are the main active components that are derived from the rhizome of Curcuma longa, which is a commonly used spice in curry dishes
Since the p16/Rb signaling pathway was indicated to play a crucial role in cellular senescence [24], we examined the effects of BDMC on p16 and its effector, retinoblastoma protein (Rb)
This premature senescence resulted from accumulation of random damage and loss of repair function caused by reactive oxygen species (ROS), and shared common features with replicative senescence [31]

Summary

Introduction

Curcuminoids, including curcumin, demethoxycurcumin, and bisdemethoxycurcumin (BDMC), are the main active components that are derived from the rhizome of Curcuma longa, which is a commonly used spice in curry dishes. Extensive studies have shown that curcuminoids possess a wide spectrum of therapeutic benefits with low toxicity These include protection against inflammation, carcinogens, and cardiovascular and neurodegenerative diseases. It was demonstrated that feeding with tetrahydrocurcumin, a major metabolite of curcumin, can increase the average lifespan of male C57BL/6 mice [7] These observations present curcuminoids as attractive candidates in prevention of ageing and ageing-related disorders. Increase in Sir (homolog of Sirt1) activity prolonged the lifespan of yeast, worms, and flies [16, 17], suggesting that Sirt plays a crucial role in ageing and ageing-related diseases Since polyphenolic compounds, such as curcuminoids, have beneficial effects on ageing-associated disorders, this raised the possibility that Sirt functions as a mediator for the effects of curcuminoids. In this study, we explored the effects of BDMC on oxidative stress-induced premature senescence as well as its effects on Sirt

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